Asif Khurshid Qazi | INDIAN INSTITUTE OF INTEGRATIVE MEDICINE (original) (raw)
Papers by Asif Khurshid Qazi
Chemico-Biological Interactions, 2016
The ethyl acetate extract from the fermentation broth of an actinomycete strain, identified as St... more The ethyl acetate extract from the fermentation broth of an actinomycete strain, identified as Streptomyces scabrisporus isolated from soil of Kashmir Himalayas-India, exhibited significant cytotoxic activity against a panel of human cancer cell lines. The active fraction subjected to column chromatography led to the isolation of pharmacologically potent anticancer compound whose structure was established to be alborixin on the basis of spectral data analysis. The compound exhibited antiproliferative activity against panel of cell lines
Phytomedicine, 2013
The objective of the study was to investigate the anti cancer activity of a lectin isolated from ... more The objective of the study was to investigate the anti cancer activity of a lectin isolated from Lotus corniculatus seeds. A tetrameric 70 kDa galactose specific lectin was purified using two step simple purification protocol which involved affinity chromatography on AF-BlueHC650M and gel filtration on Sephadex G-100. The lectin was adsorbed on AF-BlueHC650M and desorbed using 1 M NaCl in the starting buffer. Gel filtration on Sephadex G-100 yielded a major peak absorbance that gave two bands of 15 kDa and 20 kDa in SDS PAGE. Hemagglutination activity was completely preserved, when the temperature was in the range of 20-60 • C. However, drastic reduction in activity occurred at temperatures above 60 • C. Full hemagglutination activity was retained at ambient pH 4-12. Thereafter no activity was observed above pH 13. Hemaglutination of the lectin was inhibited by d-galactose. The lectin showed a strong antiproliferative activity towards human leukemic (THP-1) cancer cells followed by lung cancer (HOP62) cells and HCT116 with an IC 50 of 39 g/ml and 50 g/ml and 60 g/ml respectively. Flow cytometry analysis showed an increase in the percentage of cells in sub G0G1 phase confirming that Lotus corniculatus lectin induced apoptosis. Morphological observations showed that Lotus corniculatus lectin (LCL) treated THP-1 cells displayed apparent apoptosis characteristics such as nuclear fragmentation, appearance of membrane enclosed apoptotic bodies and DNA fragmentation. Lotus corniculatus lectin (LCL) effectively inhibits the cell migration in a dose dependent manner as indicated by the wound healing assay.
Phytomedicine, 2013
The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo... more The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (Miapaca-2). The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays. The results were comparable to standard antioxidants like ␣-tocopherol, catechin and BHT used in such experiments. Antioxidant potential of G. kurroo may be attributed to the presence of high phenolic and flavonoid content (73 ± 1.02 and 46 ± 2.05 mg/g extract respectively). The anti-proliferative property of Gentiana kurroo root extract was determined by sulphorhodamine B (SRB) assay against Human colon cancer cell line (HCT-116), Lung carcinoma cell line (A-549), Pancreatic cancer cell line (Miapaca-2), Lung cancer cell line (HOP-62) and acute monocytic leukaemia cell line (THP-1). G. kurroo root extract inhibited cancer cell growth depending upon the cell line used and in a dose dependent manner. The extract induced cell cycle arrest in Miapaca-2 cells at G 0 /G 1 phase of the cell cycle. The population of apoptotic cells increased from 11.4% in case of control to 49.6% at 100 g/ml of G. kurroo root extract. The extract also induced a remarkable decrease in mitochondrial membrane potential (« m) leading to apoptosis of cancer cells used. The main chemical constituents identified by the liquid chromatography-tandem mass spectrometry (LC-ESI-MSMS) were found to be iridoid glucosides (iridoids and secoiridoids), xanthones and flavonoids. Iridoid glucosides are the bitter principles of Gentiana species.
The HLA complex is highly polymorphic genes located on the short arm of chromosome 6 and also kno... more The HLA complex is highly polymorphic genes located on the short arm of chromosome 6 and also known as the major histocompatibility complex (MHC). MHC is found to present antigens to T cells as part of an immune response most likely found in autoimmune disease i.e Celiac disease (CD). Celiac disease (CD) is an immune-based, chronic inflammatory disorder of the small bowel mucosa, which occurs in genetically predisposed individuals precipitated by the ingestion of gluten, the major storage protein of wheat and similar grains. We aimed at identification and evaluation of HLA “DQ2” and “DQ8” heterodimers in human subjects and determination of prevalence of celiac disease in ethnic group of northernmost geographical region of the Indian subcontinent i.e. Kashmir. In this book we established that majority of the subjects under study are susceptible to celiac disease and notably females are more susceptible as compared to males. Findings of the recent work could possibly aid in better und...
Biointerface Research in Applied Chemistry, 2021
Prunus cerasus L (Sour cherries) contain diverse secondary metabolites which exhibit various biol... more Prunus cerasus L (Sour cherries) contain diverse secondary metabolites which exhibit various biological activities, including anticancer, antioxidant, and anti-inflammatory properties. The present study aimed to determine the anticancer efficacy of four compounds, quercetin, daidzin, rutin, and chlorogenic acid, isolated from Prunus cerasus fruit. The antiproliferative activity of four cherry isolates was determined against five different cancer cell lines (NCI-H322, A549, THP-1, MCF-7, and PC-3) by Tetrazolium bromide assay, followed by apoptosis Cell cycle analyses, mitochondrial membrane potential, cell migration test, and in vivo Ehrlich Ascites Carcinoma studies using potent bioactive lead. The cytotoxicity profile of the four molecules demonstrated that quercetin induced significant cell growth inhibition in all cancer cell lines with paramount 79% cytotoxicity against NCI-H322 lung cancer cells (IC50 value 24μM). Incubation of NCI-H322 cells with quercetin showed a concentrat...
JMS SKIMS
MicroRNAs (miRNAs) contribute to cellular homeostasis and differentiation in many ways, and there... more MicroRNAs (miRNAs) contribute to cellular homeostasis and differentiation in many ways, and therefore play an important role in many pathophysiological events. The knowledge of small non-coding RNAmolecules has developed our understanding towards basic processes of cancer biology and the molecular mechanisms underlying tumor initiation and progression. MiRNA research field has grown to be more and more attractive as evidence is emerging that miRNAs possibly play vital regulatory roles in all fundamental biological processes. Notably, as research continues to reveal the mechanisms underlying cancer therapy efficacy, it is apparent that miRNAs contribute to responses to drug therapy and are themselves modified by drug therapy. One important field for miRNA research is to identify functions of miRNAs and the associated signaling pathways in the initiation, progression, metastasis and drug-resistance of tumors in order to propose novel, efficient target based therapeutics that directly ...
Oncotarget, Jan 28, 2017
The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and n... more The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand brea...
Genes & cancer, 2016
MUC4 is a transmembrane mucin lining the normal colonic epithelium. The aberrant/de novo over-exp... more MUC4 is a transmembrane mucin lining the normal colonic epithelium. The aberrant/de novo over-expression of MUC4 is well documented in malignancies of the pancreas, ovary and breast. However, studies have reported the loss of MUC4 expression in the majority of colorectal cancers (CRCs). A MUC4 promoter analysis showed the presence of three putative TCF/LEF sites, implying a possible regulation by the Wnt/β-catenin pathway, which has been shown to drive CRC progression. Thus, the objective of our study was to determine whether MUC4 is regulated by β-catenin in CRC. We first knocked down (KD) β-catenin in three CRC cell lines; LS180, HCT-8 and HCT116, which resulted in increased MUC4 transcript and MUC4 protein. Additionally, the overexpression of stabilized mutant β-catenin in LS180 and HCT-8 resulted in a decrease in MUC4 expression. Immunohistochemistry (IHC) of mouse colon tissue harboring tubular adenomas and high grade dysplasia showed dramatically reduced Muc4 in lesions relati...
Fruits, Vegetables, and Herbs, 2016
Tetrahedron Letters, 2013
ABSTRACT The chromone alkaloid dysoline (1), a new regioisomer of rohitukine (2) along with rohit... more ABSTRACT The chromone alkaloid dysoline (1), a new regioisomer of rohitukine (2) along with rohitukine and rohitukine-N-oxide (3) were isolated from the stem barks of Dysoxylum binectariferum. The structure of dysoline (1) was determined by extensive 2D-NMR studies and the absolute configuration was established by NOESY and CD spectra. Dysoline (1) consisted of a 5,7-dihydroxy-2-methylchromone nucleus substituted with a 2′-hydroxylated N-Me piperidine ring at the C-6 position. Dysoline differs from rohitukine by the position of the piperidine ring on the chromone nucleus. Dysoline displayed promising cytotoxicity in HT1080 fibrosarcoma cells with an IC50 of 0.21 μM, and also displayed significant inhibition of proinflammatory cytokines TNF-α and IL-6.
Carcinogenesis, Jan 15, 2018
Cancer remains a leading cause of death in the United States and around the world. Although the c... more Cancer remains a leading cause of death in the United States and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola, or guanabana. Extracts from the fruit, bark, seeds, roots, and leaves of graviola, along with several other Annonaceous...
Http Dx Doi Org 10 1080 01635581 2015 967876, Nov 25, 2014
The objective of this study was to check the anticancer activity of purified protease inhibitors ... more The objective of this study was to check the anticancer activity of purified protease inhibitors of Lavatera cashmeriana viz LC-pi I, II, III, and IV (Lavatera cashmeriana protease inhibitors) on A549 (lung) cell. It was found that LC-pi I and II significantly inhibited the proliferation of A549 cells with IC 50 value of 54 mg/ ml and 38mg/ml, respectively, whereas inhibition by LC-pi III and IV was negligible. LC-pi I and II were further found to inhibit formation of colonies in a dose-dependent manner. Also, both inhibitors were found to induce apoptosis causing chromatin condensation and DNA fragmentation, without loss of mitochondrial membrane potential. Cell cycle revealed a significant increase of subG 0 /G 1 phase cells that are apoptotic cells. We also demonstrated a dose-dependent decrease in migration of A549 cells on cell migration assay by both inhibitors. Taken together, we demonstrate that LC-pi I and II inhibited proliferation through arresting cells before apoptosis, inducing apoptosis and inhibiting cell migration in human lung cancer cells, but the study warrants further investigation. Our results support the notion that plant protease inhibitors may have the potential to advance as chemopreventive agents.
Cancer Letters, 2016
Phosphatidylinositol 3-kinase (PI3K) pathway drives cancer progression through direct regulation ... more Phosphatidylinositol 3-kinase (PI3K) pathway drives cancer progression through direct regulation of most oncogenic properties. Here, we report that PI3K pathway signaling up-regulates cancer cell proliferation, metastasis and angiogenesis through modulation of cancer metabolism. These oncogenic metabolic processes were disrupted, by a novel PI3K inhibitor, 3-Dihydro-2-(naphthalene-1-yl) quinazolin-4(1H)-one (DHNQ) in colon cancer cells. DHNQ inhibited the Warburg effect and lipid synthesis by reducing gene expression of glycolytic and lipogenesis regulatory enzymes. This downregulation at gene level by DHNQ inhibited metabolic flux to repress proliferation, migration and invasion characteristics of colon cancer. Furthermore, the metabolic attenuation caused repression of in vitro/in vivo angiogenesis providing new insights in PI3K regulated angiogenesis via metabolic alterations. Our results suggest that multifaceted targeting of oncogenic metabolism by their upstream PI3K regulatory signaling may be an effective cancer treatment approach.
Molecular Carcinogenesis, 2016
Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is responsible for initiation, chemo-re... more Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is responsible for initiation, chemo-resistance, and poor prognosis of colorectal cancer (CRC). Therefore, PI3K pathway inhibition can provide a plausible way of attaining CRC treatment. We report PI3K target specific synthesis and selection of a potent molecule, that is, 2,3-dihydro-2-(naphthalene-1-yl) quinazolin-4(1H)-one (DHNQ) from quinazolinone series based on the structural activity relationship after evaluation in diverse cancers. This molecule inhibited the PI3K enzyme activity and transcriptional as well as translational expression levels in colorectal cancer (CRC) models. This was associated with subsequent decrease in phosphorylation of its downstream effector proteins, that is, p-Akt((Ser-473)) and p-mTORC1((Ser-2448)) and decreased ERK signaling. Furthermore, DHNQ decreased expression of cyclins that caused G1 arrest and decreased Bcl-2/Bax ratio after mitochondrial membrane potential loss, reactive oxygen species generation, and an increase in cytosolic Ca(2+) loads that is responsible for the decreased CRC cell proliferation and survival. These biochemical changes triggered apoptotic cell death with altered autophagic Beclin-1 and LC3β expression. It seemed that the PI3K-Akt signaling regulated apoptosis and autophagy through different mechanisms but mTORC1 mediated autophagy appeared not to be involved in the cell death induction by DHNQ. The molecule also showed significant anticancer efficacy in in vivo tumor models without any mortality indicating its non-toxic nature with possible clinical significance. Overall, the selective elucidation of DHNQ molecular mechanism will provide the possible strategies for the clinical development in CRC that may respond to this specific, potent and novel P13K inhibitor. © 2016 Wiley Periodicals, Inc.
Compounds with unique liphagane meroterpenoid scaffold having boronic acid functionality in the s... more Compounds with unique liphagane meroterpenoid scaffold having boronic acid functionality in the skeleton are described [formula 1] together with pharmacological potential of these compounds as anticancer agents. A method of preparation and inhibiting the activity of phosphoinositide-3-kinase (PI3K-alpha and beta) has been presented. In particular, the invention describes a method of inhibiting PI3K isoforms, wherein the compounds are novel structures based on liphagane scaffold with unique boronic acid functionality. The methods and uses thereof are described herein this invention. The claimed Markush formula is: [Formular 1]. Y can be O, NH, NR, S; Representative compounds are: [Compounds A, B, C, D]
Phytomedicine j o u r n a l h o m e p a g e : w w w . e l s e v i e r . d e / p h y m e d Inducti... more Phytomedicine j o u r n a l h o m e p a g e : w w w . e l s e v i e r . d e / p h y m e d Induction of apoptosis in human pancreatic MiaPaCa-2 cells through the loss of mitochondrial membrane potential (« m) by Gentiana kurroo root extract and LC-ESI-MS analysis of its principal constituents a b s t r a c t The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (MiaPaCa-2). The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays. The results were comparable to standard antioxidants like -tocopherol, catechin and BHT used in such experiments. Antioxidant potential of G. kurroo may be attributed to the presence of high phe-nolic and flavonoid content (73 ± 1.02 and 46 ± 2.05 mg/g extract...
Drug Research, 2015
The present study explores the fungal endophytes from selected high value medicinal plants to che... more The present study explores the fungal endophytes from selected high value medicinal plants to check their activities at in-vitro and in-vivo level. The in-vitro cytotoxicity of selected endophytes revealed potent growth inhibition against human cancer cell lines of leukemia (THP-1), lung (A549), prostate (PC-3), colon (Caco-2), neuroblastoma (IMR-32) and breast (MCF-7) at a concentration of 100 µg/ml. Among them the endophytic strains i. e., IIIM2, IIIM3, IIIM7 and IIIM8 showed most significant growth inhibition against colon (Caco-2), prostate (PC-3), lung (A549) and leukemia (THP-1) cancer cell lines. At the in-vivo level maximum (58.95%) tumor growth inhibition was documented with the extract of IIIM2 against Ehrlich Ascites Carcinoma mouse modal. All the potent fungal endophytic strains were characterized using ITS 4 and ITS 5 region sequencing and phylogenetic analysis was ascertained among them. This paper confirms the 2 elite endophytic fungal strains, IIIM2 and IIIM8, have the potential to act as a source of new anticancer compounds.
Org. Biomol. Chem., 2015
Colchicine (1), a nature-derived microtubule polymerization inhibitor, develops multi-drug resist... more Colchicine (1), a nature-derived microtubule polymerization inhibitor, develops multi-drug resistance in tumor cells due to its P-gp substrate and induction activity, which in turn leads to its rapid efflux from tumor cells. This auto-induction of the efflux of colchicine remains a major challenge to medicinal chemists. Based on structure-based molecular modeling, a series of new colchicine derivatives were designed and synthesized with a potential for reduced P-gp induction liability. Screening of the prepared derivatives for P-gp induction activity revealed that a number of derivatives possess remarkably lower P-gp-induction activity (>90% intracellular accumulation of rhodamine 123 in LS-180 cells) compared to the parent natural product colchicine (62% Rh123 accumulation in LS-180 cells). The reduced P-gpinduction activity of new derivatives may be due to their reduced ability to interact and change the conformation of P-gp. The synthesized derivatives were then screened for antiproliferative activity against two colon cancer cell lines including HCT-116 and Colo-205. The derivative 4o showed potent cytotoxicity in HCT-116 cells with IC 50 of 0.04 µM with significantly reduced P-gp induction liability. Compound 4o also inhibited microtubule assembly and induced expression of pro-apoptotic protein p21. In an Ehrlich solid tumor mice model, compound 4o showed 38% TGI with no mortality at 2 mg kg −1 dose (oral). Compound 4o, with potent in vitro and in vivo anticancer activity, significantly reduced P-gp induction activity and its excellent physicochemical and pharmacokinetic properties open up new opportunities for the colchicine scaffold. † IIIM Publication number IIIM/1616/2013 ‡ Electronic supplementary information (ESI) available: Spectra of all compounds. See
Chemico-Biological Interactions, 2016
The ethyl acetate extract from the fermentation broth of an actinomycete strain, identified as St... more The ethyl acetate extract from the fermentation broth of an actinomycete strain, identified as Streptomyces scabrisporus isolated from soil of Kashmir Himalayas-India, exhibited significant cytotoxic activity against a panel of human cancer cell lines. The active fraction subjected to column chromatography led to the isolation of pharmacologically potent anticancer compound whose structure was established to be alborixin on the basis of spectral data analysis. The compound exhibited antiproliferative activity against panel of cell lines
Phytomedicine, 2013
The objective of the study was to investigate the anti cancer activity of a lectin isolated from ... more The objective of the study was to investigate the anti cancer activity of a lectin isolated from Lotus corniculatus seeds. A tetrameric 70 kDa galactose specific lectin was purified using two step simple purification protocol which involved affinity chromatography on AF-BlueHC650M and gel filtration on Sephadex G-100. The lectin was adsorbed on AF-BlueHC650M and desorbed using 1 M NaCl in the starting buffer. Gel filtration on Sephadex G-100 yielded a major peak absorbance that gave two bands of 15 kDa and 20 kDa in SDS PAGE. Hemagglutination activity was completely preserved, when the temperature was in the range of 20-60 • C. However, drastic reduction in activity occurred at temperatures above 60 • C. Full hemagglutination activity was retained at ambient pH 4-12. Thereafter no activity was observed above pH 13. Hemaglutination of the lectin was inhibited by d-galactose. The lectin showed a strong antiproliferative activity towards human leukemic (THP-1) cancer cells followed by lung cancer (HOP62) cells and HCT116 with an IC 50 of 39 g/ml and 50 g/ml and 60 g/ml respectively. Flow cytometry analysis showed an increase in the percentage of cells in sub G0G1 phase confirming that Lotus corniculatus lectin induced apoptosis. Morphological observations showed that Lotus corniculatus lectin (LCL) treated THP-1 cells displayed apparent apoptosis characteristics such as nuclear fragmentation, appearance of membrane enclosed apoptotic bodies and DNA fragmentation. Lotus corniculatus lectin (LCL) effectively inhibits the cell migration in a dose dependent manner as indicated by the wound healing assay.
Phytomedicine, 2013
The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo... more The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (Miapaca-2). The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays. The results were comparable to standard antioxidants like ␣-tocopherol, catechin and BHT used in such experiments. Antioxidant potential of G. kurroo may be attributed to the presence of high phenolic and flavonoid content (73 ± 1.02 and 46 ± 2.05 mg/g extract respectively). The anti-proliferative property of Gentiana kurroo root extract was determined by sulphorhodamine B (SRB) assay against Human colon cancer cell line (HCT-116), Lung carcinoma cell line (A-549), Pancreatic cancer cell line (Miapaca-2), Lung cancer cell line (HOP-62) and acute monocytic leukaemia cell line (THP-1). G. kurroo root extract inhibited cancer cell growth depending upon the cell line used and in a dose dependent manner. The extract induced cell cycle arrest in Miapaca-2 cells at G 0 /G 1 phase of the cell cycle. The population of apoptotic cells increased from 11.4% in case of control to 49.6% at 100 g/ml of G. kurroo root extract. The extract also induced a remarkable decrease in mitochondrial membrane potential (« m) leading to apoptosis of cancer cells used. The main chemical constituents identified by the liquid chromatography-tandem mass spectrometry (LC-ESI-MSMS) were found to be iridoid glucosides (iridoids and secoiridoids), xanthones and flavonoids. Iridoid glucosides are the bitter principles of Gentiana species.
The HLA complex is highly polymorphic genes located on the short arm of chromosome 6 and also kno... more The HLA complex is highly polymorphic genes located on the short arm of chromosome 6 and also known as the major histocompatibility complex (MHC). MHC is found to present antigens to T cells as part of an immune response most likely found in autoimmune disease i.e Celiac disease (CD). Celiac disease (CD) is an immune-based, chronic inflammatory disorder of the small bowel mucosa, which occurs in genetically predisposed individuals precipitated by the ingestion of gluten, the major storage protein of wheat and similar grains. We aimed at identification and evaluation of HLA “DQ2” and “DQ8” heterodimers in human subjects and determination of prevalence of celiac disease in ethnic group of northernmost geographical region of the Indian subcontinent i.e. Kashmir. In this book we established that majority of the subjects under study are susceptible to celiac disease and notably females are more susceptible as compared to males. Findings of the recent work could possibly aid in better und...
Biointerface Research in Applied Chemistry, 2021
Prunus cerasus L (Sour cherries) contain diverse secondary metabolites which exhibit various biol... more Prunus cerasus L (Sour cherries) contain diverse secondary metabolites which exhibit various biological activities, including anticancer, antioxidant, and anti-inflammatory properties. The present study aimed to determine the anticancer efficacy of four compounds, quercetin, daidzin, rutin, and chlorogenic acid, isolated from Prunus cerasus fruit. The antiproliferative activity of four cherry isolates was determined against five different cancer cell lines (NCI-H322, A549, THP-1, MCF-7, and PC-3) by Tetrazolium bromide assay, followed by apoptosis Cell cycle analyses, mitochondrial membrane potential, cell migration test, and in vivo Ehrlich Ascites Carcinoma studies using potent bioactive lead. The cytotoxicity profile of the four molecules demonstrated that quercetin induced significant cell growth inhibition in all cancer cell lines with paramount 79% cytotoxicity against NCI-H322 lung cancer cells (IC50 value 24μM). Incubation of NCI-H322 cells with quercetin showed a concentrat...
JMS SKIMS
MicroRNAs (miRNAs) contribute to cellular homeostasis and differentiation in many ways, and there... more MicroRNAs (miRNAs) contribute to cellular homeostasis and differentiation in many ways, and therefore play an important role in many pathophysiological events. The knowledge of small non-coding RNAmolecules has developed our understanding towards basic processes of cancer biology and the molecular mechanisms underlying tumor initiation and progression. MiRNA research field has grown to be more and more attractive as evidence is emerging that miRNAs possibly play vital regulatory roles in all fundamental biological processes. Notably, as research continues to reveal the mechanisms underlying cancer therapy efficacy, it is apparent that miRNAs contribute to responses to drug therapy and are themselves modified by drug therapy. One important field for miRNA research is to identify functions of miRNAs and the associated signaling pathways in the initiation, progression, metastasis and drug-resistance of tumors in order to propose novel, efficient target based therapeutics that directly ...
Oncotarget, Jan 28, 2017
The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and n... more The dismal prognosis of locally advanced and metastatic squamous cell carcinoma of the head and neck (HNSCC) is primarily due to the development of resistance to chemoradiation therapy (CRT). Deregulation of Epidermal Growth Factor Receptor (EGFR) signaling is involved in HNSCC pathogenesis by regulating cell survival, cancer stem cells (CSCs), and resistance to CRT. Here we investigated the radiosensitizing activity of the pan-EGFR inhibitor afatinib in HNSCC in vitro and in vivo. Our results showed strong antiproliferative effects of afatinib in HNSCC SCC1 and SCC10B cells, compared to immortalized normal oral epithelial cells MOE1a and MOE1b. Comparative analysis revealed stronger antitumor effects with afatinib than observed with erlotinib. Furthermore, afatinib enhanced in vitro radiosensitivity of SCC1 and SCC10B cells by inducing mesenchymal to epithelial transition, G1 cell cycle arrest, and the attenuating ionizing radiation (IR)-induced activation of DNA double strand brea...
Genes & cancer, 2016
MUC4 is a transmembrane mucin lining the normal colonic epithelium. The aberrant/de novo over-exp... more MUC4 is a transmembrane mucin lining the normal colonic epithelium. The aberrant/de novo over-expression of MUC4 is well documented in malignancies of the pancreas, ovary and breast. However, studies have reported the loss of MUC4 expression in the majority of colorectal cancers (CRCs). A MUC4 promoter analysis showed the presence of three putative TCF/LEF sites, implying a possible regulation by the Wnt/β-catenin pathway, which has been shown to drive CRC progression. Thus, the objective of our study was to determine whether MUC4 is regulated by β-catenin in CRC. We first knocked down (KD) β-catenin in three CRC cell lines; LS180, HCT-8 and HCT116, which resulted in increased MUC4 transcript and MUC4 protein. Additionally, the overexpression of stabilized mutant β-catenin in LS180 and HCT-8 resulted in a decrease in MUC4 expression. Immunohistochemistry (IHC) of mouse colon tissue harboring tubular adenomas and high grade dysplasia showed dramatically reduced Muc4 in lesions relati...
Fruits, Vegetables, and Herbs, 2016
Tetrahedron Letters, 2013
ABSTRACT The chromone alkaloid dysoline (1), a new regioisomer of rohitukine (2) along with rohit... more ABSTRACT The chromone alkaloid dysoline (1), a new regioisomer of rohitukine (2) along with rohitukine and rohitukine-N-oxide (3) were isolated from the stem barks of Dysoxylum binectariferum. The structure of dysoline (1) was determined by extensive 2D-NMR studies and the absolute configuration was established by NOESY and CD spectra. Dysoline (1) consisted of a 5,7-dihydroxy-2-methylchromone nucleus substituted with a 2′-hydroxylated N-Me piperidine ring at the C-6 position. Dysoline differs from rohitukine by the position of the piperidine ring on the chromone nucleus. Dysoline displayed promising cytotoxicity in HT1080 fibrosarcoma cells with an IC50 of 0.21 μM, and also displayed significant inhibition of proinflammatory cytokines TNF-α and IL-6.
Carcinogenesis, Jan 15, 2018
Cancer remains a leading cause of death in the United States and around the world. Although the c... more Cancer remains a leading cause of death in the United States and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola, or guanabana. Extracts from the fruit, bark, seeds, roots, and leaves of graviola, along with several other Annonaceous...
Http Dx Doi Org 10 1080 01635581 2015 967876, Nov 25, 2014
The objective of this study was to check the anticancer activity of purified protease inhibitors ... more The objective of this study was to check the anticancer activity of purified protease inhibitors of Lavatera cashmeriana viz LC-pi I, II, III, and IV (Lavatera cashmeriana protease inhibitors) on A549 (lung) cell. It was found that LC-pi I and II significantly inhibited the proliferation of A549 cells with IC 50 value of 54 mg/ ml and 38mg/ml, respectively, whereas inhibition by LC-pi III and IV was negligible. LC-pi I and II were further found to inhibit formation of colonies in a dose-dependent manner. Also, both inhibitors were found to induce apoptosis causing chromatin condensation and DNA fragmentation, without loss of mitochondrial membrane potential. Cell cycle revealed a significant increase of subG 0 /G 1 phase cells that are apoptotic cells. We also demonstrated a dose-dependent decrease in migration of A549 cells on cell migration assay by both inhibitors. Taken together, we demonstrate that LC-pi I and II inhibited proliferation through arresting cells before apoptosis, inducing apoptosis and inhibiting cell migration in human lung cancer cells, but the study warrants further investigation. Our results support the notion that plant protease inhibitors may have the potential to advance as chemopreventive agents.
Cancer Letters, 2016
Phosphatidylinositol 3-kinase (PI3K) pathway drives cancer progression through direct regulation ... more Phosphatidylinositol 3-kinase (PI3K) pathway drives cancer progression through direct regulation of most oncogenic properties. Here, we report that PI3K pathway signaling up-regulates cancer cell proliferation, metastasis and angiogenesis through modulation of cancer metabolism. These oncogenic metabolic processes were disrupted, by a novel PI3K inhibitor, 3-Dihydro-2-(naphthalene-1-yl) quinazolin-4(1H)-one (DHNQ) in colon cancer cells. DHNQ inhibited the Warburg effect and lipid synthesis by reducing gene expression of glycolytic and lipogenesis regulatory enzymes. This downregulation at gene level by DHNQ inhibited metabolic flux to repress proliferation, migration and invasion characteristics of colon cancer. Furthermore, the metabolic attenuation caused repression of in vitro/in vivo angiogenesis providing new insights in PI3K regulated angiogenesis via metabolic alterations. Our results suggest that multifaceted targeting of oncogenic metabolism by their upstream PI3K regulatory signaling may be an effective cancer treatment approach.
Molecular Carcinogenesis, 2016
Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is responsible for initiation, chemo-re... more Phosphatidylinositol-3-kinase (PI3K) pathway deregulation is responsible for initiation, chemo-resistance, and poor prognosis of colorectal cancer (CRC). Therefore, PI3K pathway inhibition can provide a plausible way of attaining CRC treatment. We report PI3K target specific synthesis and selection of a potent molecule, that is, 2,3-dihydro-2-(naphthalene-1-yl) quinazolin-4(1H)-one (DHNQ) from quinazolinone series based on the structural activity relationship after evaluation in diverse cancers. This molecule inhibited the PI3K enzyme activity and transcriptional as well as translational expression levels in colorectal cancer (CRC) models. This was associated with subsequent decrease in phosphorylation of its downstream effector proteins, that is, p-Akt((Ser-473)) and p-mTORC1((Ser-2448)) and decreased ERK signaling. Furthermore, DHNQ decreased expression of cyclins that caused G1 arrest and decreased Bcl-2/Bax ratio after mitochondrial membrane potential loss, reactive oxygen species generation, and an increase in cytosolic Ca(2+) loads that is responsible for the decreased CRC cell proliferation and survival. These biochemical changes triggered apoptotic cell death with altered autophagic Beclin-1 and LC3β expression. It seemed that the PI3K-Akt signaling regulated apoptosis and autophagy through different mechanisms but mTORC1 mediated autophagy appeared not to be involved in the cell death induction by DHNQ. The molecule also showed significant anticancer efficacy in in vivo tumor models without any mortality indicating its non-toxic nature with possible clinical significance. Overall, the selective elucidation of DHNQ molecular mechanism will provide the possible strategies for the clinical development in CRC that may respond to this specific, potent and novel P13K inhibitor. © 2016 Wiley Periodicals, Inc.
Compounds with unique liphagane meroterpenoid scaffold having boronic acid functionality in the s... more Compounds with unique liphagane meroterpenoid scaffold having boronic acid functionality in the skeleton are described [formula 1] together with pharmacological potential of these compounds as anticancer agents. A method of preparation and inhibiting the activity of phosphoinositide-3-kinase (PI3K-alpha and beta) has been presented. In particular, the invention describes a method of inhibiting PI3K isoforms, wherein the compounds are novel structures based on liphagane scaffold with unique boronic acid functionality. The methods and uses thereof are described herein this invention. The claimed Markush formula is: [Formular 1]. Y can be O, NH, NR, S; Representative compounds are: [Compounds A, B, C, D]
Phytomedicine j o u r n a l h o m e p a g e : w w w . e l s e v i e r . d e / p h y m e d Inducti... more Phytomedicine j o u r n a l h o m e p a g e : w w w . e l s e v i e r . d e / p h y m e d Induction of apoptosis in human pancreatic MiaPaCa-2 cells through the loss of mitochondrial membrane potential (« m) by Gentiana kurroo root extract and LC-ESI-MS analysis of its principal constituents a b s t r a c t The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (MiaPaCa-2). The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays. The results were comparable to standard antioxidants like -tocopherol, catechin and BHT used in such experiments. Antioxidant potential of G. kurroo may be attributed to the presence of high phe-nolic and flavonoid content (73 ± 1.02 and 46 ± 2.05 mg/g extract...
Drug Research, 2015
The present study explores the fungal endophytes from selected high value medicinal plants to che... more The present study explores the fungal endophytes from selected high value medicinal plants to check their activities at in-vitro and in-vivo level. The in-vitro cytotoxicity of selected endophytes revealed potent growth inhibition against human cancer cell lines of leukemia (THP-1), lung (A549), prostate (PC-3), colon (Caco-2), neuroblastoma (IMR-32) and breast (MCF-7) at a concentration of 100 µg/ml. Among them the endophytic strains i. e., IIIM2, IIIM3, IIIM7 and IIIM8 showed most significant growth inhibition against colon (Caco-2), prostate (PC-3), lung (A549) and leukemia (THP-1) cancer cell lines. At the in-vivo level maximum (58.95%) tumor growth inhibition was documented with the extract of IIIM2 against Ehrlich Ascites Carcinoma mouse modal. All the potent fungal endophytic strains were characterized using ITS 4 and ITS 5 region sequencing and phylogenetic analysis was ascertained among them. This paper confirms the 2 elite endophytic fungal strains, IIIM2 and IIIM8, have the potential to act as a source of new anticancer compounds.
Org. Biomol. Chem., 2015
Colchicine (1), a nature-derived microtubule polymerization inhibitor, develops multi-drug resist... more Colchicine (1), a nature-derived microtubule polymerization inhibitor, develops multi-drug resistance in tumor cells due to its P-gp substrate and induction activity, which in turn leads to its rapid efflux from tumor cells. This auto-induction of the efflux of colchicine remains a major challenge to medicinal chemists. Based on structure-based molecular modeling, a series of new colchicine derivatives were designed and synthesized with a potential for reduced P-gp induction liability. Screening of the prepared derivatives for P-gp induction activity revealed that a number of derivatives possess remarkably lower P-gp-induction activity (>90% intracellular accumulation of rhodamine 123 in LS-180 cells) compared to the parent natural product colchicine (62% Rh123 accumulation in LS-180 cells). The reduced P-gpinduction activity of new derivatives may be due to their reduced ability to interact and change the conformation of P-gp. The synthesized derivatives were then screened for antiproliferative activity against two colon cancer cell lines including HCT-116 and Colo-205. The derivative 4o showed potent cytotoxicity in HCT-116 cells with IC 50 of 0.04 µM with significantly reduced P-gp induction liability. Compound 4o also inhibited microtubule assembly and induced expression of pro-apoptotic protein p21. In an Ehrlich solid tumor mice model, compound 4o showed 38% TGI with no mortality at 2 mg kg −1 dose (oral). Compound 4o, with potent in vitro and in vivo anticancer activity, significantly reduced P-gp induction activity and its excellent physicochemical and pharmacokinetic properties open up new opportunities for the colchicine scaffold. † IIIM Publication number IIIM/1616/2013 ‡ Electronic supplementary information (ESI) available: Spectra of all compounds. See