Abeer Ashmawy - Academia.edu (original) (raw)

Papers by Abeer Ashmawy

Research paper thumbnail of siRNA Mediated-hTERT Knockdown Impedes Proliferation of Mammalian Cancer MCF7 and HepG2 Cells

The Journal of American Science, 2011

Research paper thumbnail of Changes Of P21 And Bcl-2 During Induction Of Bladder Inflammation And/Or Bladder Carcinogenesis

The Egyptian Journal of Hospital Medicine, 2012

Acetaminophen known as paracetamol (P) overdose can cause severe hepatotoxicity and even liver fa... more Acetaminophen known as paracetamol (P) overdose can cause severe hepatotoxicity and even liver failure and hepatic centrilobular necrosis in experimental animals and humans.

Research paper thumbnail of Role of Surfactants in Regulation of Cancer Growth

Research paper thumbnail of Inhibition of c-kit in Late Cirrhosis may Restore TGF-β Inhibitory Effect on Somatic Liver Stem Cells and Prevent Development of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer worldwid... more Background: Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer worldwide and the second leading cause of cancer-related death in the world. It occurs within an established background of chronic liver disease and cirrhosis. Liver fibrosis is a wound healing-like event stimulated by TGF-β following repeated and/or chronic insult and can grow into cirrhosis. Proliferation of somatic liver stem cells (SLSCs) and increased TGF-β production during chronic liver disease has been linked to the risk for HCC development. The cross-talk between TGF-βreceptor (serine/threonine) and tyrosine kinase receptors drew attentions to a probable relationship between TGF-β and c-kit gene expressed by SLSCs which might explore the biology and etiology of HCC if it is uncovered. Aim: SLSCs were isolated from tumor and non-tumor (cirrhotic) liver tissue to study the effect of TGF-β on tumorand non-tumor-derived SLSCs. Material and Methods: Tumorand non-tumor SLSCs were isolated fro...

Research paper thumbnail of A Cost-Saving Technique of Human Somatic Liver Stem Cells Isolation for Ex Vivo Propagation and Characterization

1 Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt 2 Depar... more 1 Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy and Drug Manufacturing, Pharos University, Alexandria, Egypt 3 Department of Pharmaceutics, Faculty of Pharmacy, Universityof Tabuk, Tabuk, KSA 4 Department of Surgery, Faculty of Medicine, Ain Shams University, Egypt 5 Department of Pathology, National Cancer Institute, Cairo University, Cairo, Egypt *Corresponding Author Email: a_ahmed @ut.edu.sa

Research paper thumbnail of Downregulation of miR-23a and miR-24 in human hepatocellular carcinoma cells by Sorafenib via transforming growth factor-beta 1 in a SMAD dependent manner

Journal of Bioscience and Applied Research, 2019

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcrip... more MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcriptional interactions with mRNA. MiRNAs have recently considered as key regulators of various cancers including liver cancer. Sorafenib is one of the antitumor drugs for the treatment of advanced hepatocellular carcinoma. It acts as a multikinase inhibitor suppressing cell proliferation and angiogenesis. This study tries to investigate a potential microRNA-based mechanism of action of the drug by studying the effect of sorafenib on miR-23a and miR-24 levels in HCC cell lines HepG2 /Huh7 and revealing the possible drug mechanism against these oncogenic miRNAS in this study cell viability of cultured HepG2 /Huh7 after treatment with sorafenib were evaluated using Sulphorhodamine-B (SRB) assay, cell cycle and apoptosis estimated by flow cytometry assay. The caspase-3 level was determined using the ELISA assay. Moreover, miR-23a and miR-24 expressions levels analyzed by qPCR. Finally, TGF-β le...

Research paper thumbnail of Chemical composition, cytotoxicity and molecular profiling of Cordia africana Lam. on human breast cancer cell line

Natural Product Research, 2020

Metabolic profiling of the hexane extract and essential oil of Cordia africana Lam., an 9 economi... more Metabolic profiling of the hexane extract and essential oil of Cordia africana Lam., an 9 economically important agroforestry species, was analysed by GC-FID and GC-MS. 10 Cytotoxicity was assessed in MCF-7 cancer cells using sulphorhodamine-B assay. 11 Caspase-8, BcL-2 and Ki-67 levels were evaluated using enzyme-linked 12 immunosorbent assay. Forty-one compounds were identified in the hexane extract, 13 meanwhile, eighty compounds were annotated in the essential oil. n-Decane (9.52%), 14 -sitosterol (8.13%), undecane (6.32%) and palmitaldehyde (5.50 %) were the major 15 compounds identified in the hexane extract, whereas, -caryophyllene (32.0%), 16 germacrene D (10.12%) and δ-cadinene (7.20%) predominated in the essential oil. The 17 inhibitory concentrations (IC 50) of the extract and oil were 4.55 µg/mL and 12.90 18 µg/mL, respectively. Caspase-8 activity increased significantly in hexane extract 19 treated cells. Furthermore, BcL-2 and Ki-67 protein expression levels were 20 significantly decreased. Cordia africana Lam exhibits potent cytotoxicity against breast 21 cancer cell line, most likely through apoptosis regulation.

Research paper thumbnail of GC/MS Analysis and Molecular Profiling of Lemon Volatile Oil against Breast Cancer

Journal of Essential Oil Bearing Plants, 2019

Breast cancer is the most common among women cancers and the most likely to cause death. Citrus p... more Breast cancer is the most common among women cancers and the most likely to cause death. Citrus plants essential oils are reported for having potential cytotoxic activities. Thirty three and thirty five compounds were identified from leaves and green branches of Citrus limon (L.) Burm. family (Rutaceae), respectively. The main components were limonene (47.24 %; 55.23 %), geranial (14.48 %; 7.94 %) and neral (12.1 %; 6.1 %). Lemon leaf oil showed cytotoxic activity against breast carcinoma cells (MCF-7) at IC 50 of 10 % (v/v). A significant increase in the expression levels of the apoptotic protein caspase-8, a significant decrease in the expression levels of both the anti-apoptotic protein BcL-2 and the proliferative marker Ki-67 were observed (in comparison with un treated cells ; p<0.05). The docking results showed high affinity of geranial against caspase-8 and caspase-9 indicating the promising cytotoxic effect of lemon oil through enhancing apoptosis. Further studies are required to test the safety and toxicological properties of the oil as medicine.

Research paper thumbnail of MiRNAs-181a/b as Predictive biomarkers for olaparib sensitivity in triple-negative breast cancer cells

Biochemistry Letters, 2017

Triple negative breast cancer PARP, poly ADP-ribose polymerase ATM, ataxia telangiectasia mutated... more Triple negative breast cancer PARP, poly ADP-ribose polymerase ATM, ataxia telangiectasia mutated Background: spotting the scope on triple-negative breast cancer (TNBC) as the most aggressive type of breast cancer, with no targeted therapeutic options. TNBC is often characterized by having defects in DNA repair due to defects in BRCA making this cancer a rational target for the synthetic lethality of olaparib, as an inhibitory target agent of the alternative DNA repair pathway (poly ADP-ribose polymerase "PARP" inhibitor). Objectives: the present study aims to evaluate the value of miRNAs-181a/b as potential biomarkers in predicting the response of TNBC to olaparib. Methods: anti-miRNAs-181a/b was transfected into MDA-MB-231 cell line using HiPerFect transfection reagent, the transfected and untransfected cells were subjected to olaparib. The effect of miRNAs-181a/b on MDA-MB-231 treated cells with olaparib was evaluated through the detection of essential proteins involved in apoptosis and cell proliferation including Caspase-8, Bcl-2, and Ki-67. Further, the expression level of ataxia telangiectasia mutated (ATM) was determined as a functional target of miRNAs-181a/b. Results: a significant decrease in Caspase-8 activity, and Bcl-2, but a significant increase in cell survival, cell proliferation, and ATM protein were observed upon suppression of miRNAs-181a/b by their inhibitors followed by treatment with olaparib for TNBC cell line (MDA-MB-231 cells). Conclusions: our data confirmed that miRNA-181a and miRNA-181b play a critical role for detecting the sensitivity of TNBC cells to olaparib. As well as miRNAs-181a/b could be used as a potentially predictive biomarkers for response to olaparib.

Research paper thumbnail of Synthesis and biochemical studies of novel organic selenides with increased selectivity for hepatocellular carcinoma and breast adenocarcinoma

European Journal of Medicinal Chemistry, 2019

Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatoce... more Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the napthoquinone-(5), thiazol-(12), and the azobased (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, napthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.

Research paper thumbnail of Crosstalk between liver-related microRNAs and Wnt/β-catenin pathway in hepatocellular carcinoma patients

Arab Journal of Gastroenterology, 2017

Background and study aims: Hepatocellular carcinoma (HCC) is one of the most common cancers world... more Background and study aims: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with highest incidence in Asia and Africa. MicroRNAs (miRNAs), a class of non-coding single stranded RNA, which not only post transcriptionally regulate gene expression but also respond to signaling molecules to affect cell functions such as Wnt/b-catenin signaling specifically in HCC. The goal of this study is to investigate the crosstalk between Wnt/b-catenin signaling proteins and microRNAs expression in HCC patients. Patients and methods: Fresh tissue samples of 30 primary HCC patients and 10 control subjects were included. Expression level of 13 different miRNAs (miR-10a-miR-106b-miR-99a-miR-148a-miR-125b-miR-30e-miR-183-miR-155-miR-199a-miR-199a3p-miR-24-miR-122 and miR-215) were examined using real-time PCR assay. Five proteins involved in the Wnt/b-catenin pathway (b-catenin, APC, c-myc, survivin and cyclin D1) were analysed by immunohistochemistry technique. The correlation between miRNAs expression levels with protein expressions was assessed. Results: Up-regulation of miR-155 and miR-183 was reported in HCC patients compared to normal controls and this up-regulation was significantly correlated with liver cirrhosis in the case of miR-155 (p < 0.05) referring to their oncogenic activity. Down-regulation was observed for 11 miRNAs in HCC indicating their tumour suppression activity. MiRNA-10a, miR-30e, miR-215, miR-125b and miR-148a were significantly correlated with the expression of important players in Wnt/b-catenin pathway including b-catenin, APC and c-myc (p < 0.05). Detailed analysis revealed that miR-215 is associated with the grade of the disease and miR-125b is associated with HCV infection. Conclusion: Collectively, our data showed potential role of miR-10a, miR-30e, miR-215, miR-125b and miR-148a as important mediators in HCC progression. Furthermore, their association with Wnt/ b-catenin cascade proteins could be exploited to develop new therapeutic target strategies in HCC.

Research paper thumbnail of Design, synthesis and screening of 1, 2, 4-triazinone derivatives as potential antitumor agents with apoptosis inducing activity on MCF-7 breast cancer cell line

European journal of medicinal chemistry, Jan 7, 2018

Some triazinone derivatives are designed and synthesized as potential antitumor agents. Triazinon... more Some triazinone derivatives are designed and synthesized as potential antitumor agents. Triazinone derivatives 4c, 5e and 7c show potent anticancer activity over MCF-7 breast cancer cells higher than podophyllotoxin (podo) by approximate 6-fold. DNA flow cytometry analysis for the compounds 3c, 4c, 5e, 6c and 7c show a potent inhibitory activity of cell proliferation and cell cycle arrest at G/M phase. Compounds 4c, 5e and 7c exhibit low to moderate β-tubulin polymerization inhibition percentage. Meanwhile, compound 6c displayed excellent β-tubulin percentage of polymerization inhibition equivalent to that exhibited by podo. In addition, compounds 4c, 5e and 7c show strong topoisomerase (topo) II inhibitory activity in nano-molar concentration, compared to known topo inhibitor as etoposide. Finally, apoptotic inducing activity over MCF-7 of compounds 4c, 5e, 6c and 7c is due to up-regulation of p53, increased Bax/Bcl-2 ratio and caspase3/7 levels 2-fold higher than podo.

Research paper thumbnail of Chemical composition of aqueous-ethanol extract of Luffa cylindrica leaves and its effect on representation of caspase 8, caspase 3 and the proliferation marker Ki67 in intrinsic molecular sub-types of breast cancer in vitro

Chemistry & biodiversity, Jan 6, 2018

Breast cancer constitutes the second most prevalent cancer in Egypt, the problem which needs more... more Breast cancer constitutes the second most prevalent cancer in Egypt, the problem which needs more trends in treatment and treatment development either by regimen modification or introducing new drugs, the main objective of this study is to screen the effects of the aqueous-ethanol herbal extract of Luffa cylindrica leaves on different types of breast cancer cell lines representing different molecular sub-types of the disease. The major active constituents of the extract were tentatively identified by LC/MS which revealed the presence of phenolic compounds derivatives and saponin that may responsible in part for the activity of the extract. The emphasis was laid on the main apoptotic pathways as well as the extract effect on the normal cell line. Results of phytochemical investigation, cell cycle analysis and molecular analysis of apoptotic and proliferative markers have shown effective anticancer activity against MCF-7, BT-474, and MDA-MB-231 cell lines which represent three sub-typ...

Research paper thumbnail of Combinatorial synthesis, in silico , molecular and biochemical studies of tetrazole-derived organic selenides with increased selectivity against hepatocellular carcinoma

European Journal of Medicinal Chemistry, 2016

Research paper thumbnail of Transforming growth factor‑β, insulin‑like growth factor I/insulin‑like growth factor I receptor and vascular endothelial growth factor‑A: Prognostic and predictive markers in triple‑negative and non‑triple‑negative breast cancer

Molecular medicine reports, Jan 27, 2015

In the current study, the prognostic and predictive values of serum transforming growth factor‑β1... more In the current study, the prognostic and predictive values of serum transforming growth factor‑β1 (TGF‑β1), insulin‑like growth factor I (IGF‑I)/IGF‑I receptor (IGF‑IR) and vascular endothelial growth factor‑A (VEGF‑A) were evaluated in triple‑negative and non‑triple‑negative breast cancer (TNBC and non‑TNBC). The aim was to identify a group of serological biomarkers and to identify possible candidates for targeted therapy in patients with TNBC and non‑TNBC. Protein levels of TGF‑β1, IGF‑I/IGF‑IR and VEGF‑A in the serum were measured in 43 TNBC, 53 non‑TNBC and 20 normal control participants using quantitative ELISA assays. Results were correlated against standard prognostic factors, response to treatment and survival. TNBC was identified to be associated with poor prognosis and serum levels of VEGF‑A and IGF/IGF‑IR were significantly higher in the TNBC group compared with the non‑TNBC group. IGF‑IR and VEGF‑A overexpression was observed to be correlated with TGF‑β1 expression and a...

Research paper thumbnail of siRNA Mediated-hTERT Knockdown Impedes Proliferation of Mammalian Cancer MCF7 and HepG2 Cells

Journal of American Science, 2011

Research paper thumbnail of Telomere length in chronic obstructive pulmonary disease

Egyptian Journal of Bronchology, 2015

Background Telomere length (TL) is considered a biomarker of cellular aging. Chronic obstructive ... more Background Telomere length (TL) is considered a biomarker of cellular aging. Chronic obstructive pulmonary disease (COPD) is found to be associated with premature aging and the senescence hypothesis is now accepted as a molecular pathway for COPD development. Purpose The aim of this study was to measure TL in COPD patients and to study its relation to demographic data, spirometric indices, and arterial blood gases parameters. Participants and methods We measured TL using quantitative PCR in 20 patients with severe to very severe COPD and 11 age-matched and sex-matched nonsmokers. Results TL was significantly shorter in COPD patients (P < 0.001). Among COPD patients, TL was significantly shorter in current smokers than ex-smokers. In COPD patients, TL was correlated positively with SpO2%, pH (P < 0.05), PaO2 (P < 0.01), FVC% (P < 0.05) and FEV1%, and FEF25–75% (P < 0.001) and not correlated with pack-year. The BODE (Body mass index, airflow Obstruction, Dyspnea, and Ex...

Research paper thumbnail of GC/MS Analysis and Molecular Profiling of Lemon Volatile Oil against Breast Cancer

Journal of Essential Oil Bearing Plants

Research paper thumbnail of Chemical composition, cytotoxicity and molecular profiling of Cordia africana Lam. on human breast cancer cell line

Research paper thumbnail of Induction of Anti-Proliferative and Apoptotic Effects of Sorafenib Using miR-27a Inhibitor in Hepatocellular Carcinoma Cell Lines

Asian Pacific Journal of Cancer Prevention

HCC patients received systemic chemotherapeutic agents (Liu et al., 2015). Sorafenib (Nexavar) is... more HCC patients received systemic chemotherapeutic agents (Liu et al., 2015). Sorafenib (Nexavar) is a multikinase inhibitor that targets both RAF and a number of tyrosine kinases, including vascular endothelial growth factor receptors (VEGFRs), and platelet-derived growth factor receptor-β (PDGFR-β) (Wilhelm et al., 2005). Despite the fact that sorafenib has been approved in several countries worldwide for advanced HCC patients still yet the drug show unsatisfied clinical outcomes due to its severe

Research paper thumbnail of siRNA Mediated-hTERT Knockdown Impedes Proliferation of Mammalian Cancer MCF7 and HepG2 Cells

The Journal of American Science, 2011

Research paper thumbnail of Changes Of P21 And Bcl-2 During Induction Of Bladder Inflammation And/Or Bladder Carcinogenesis

The Egyptian Journal of Hospital Medicine, 2012

Acetaminophen known as paracetamol (P) overdose can cause severe hepatotoxicity and even liver fa... more Acetaminophen known as paracetamol (P) overdose can cause severe hepatotoxicity and even liver failure and hepatic centrilobular necrosis in experimental animals and humans.

Research paper thumbnail of Role of Surfactants in Regulation of Cancer Growth

Research paper thumbnail of Inhibition of c-kit in Late Cirrhosis may Restore TGF-β Inhibitory Effect on Somatic Liver Stem Cells and Prevent Development of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer worldwid... more Background: Hepatocellular carcinoma (HCC) is the fifth most frequently diagnosed cancer worldwide and the second leading cause of cancer-related death in the world. It occurs within an established background of chronic liver disease and cirrhosis. Liver fibrosis is a wound healing-like event stimulated by TGF-β following repeated and/or chronic insult and can grow into cirrhosis. Proliferation of somatic liver stem cells (SLSCs) and increased TGF-β production during chronic liver disease has been linked to the risk for HCC development. The cross-talk between TGF-βreceptor (serine/threonine) and tyrosine kinase receptors drew attentions to a probable relationship between TGF-β and c-kit gene expressed by SLSCs which might explore the biology and etiology of HCC if it is uncovered. Aim: SLSCs were isolated from tumor and non-tumor (cirrhotic) liver tissue to study the effect of TGF-β on tumorand non-tumor-derived SLSCs. Material and Methods: Tumorand non-tumor SLSCs were isolated fro...

Research paper thumbnail of A Cost-Saving Technique of Human Somatic Liver Stem Cells Isolation for Ex Vivo Propagation and Characterization

1 Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt 2 Depar... more 1 Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo, Egypt 2 Department of Pharmacology and Toxicology, Faculty of Pharmacy and Drug Manufacturing, Pharos University, Alexandria, Egypt 3 Department of Pharmaceutics, Faculty of Pharmacy, Universityof Tabuk, Tabuk, KSA 4 Department of Surgery, Faculty of Medicine, Ain Shams University, Egypt 5 Department of Pathology, National Cancer Institute, Cairo University, Cairo, Egypt *Corresponding Author Email: a_ahmed @ut.edu.sa

Research paper thumbnail of Downregulation of miR-23a and miR-24 in human hepatocellular carcinoma cells by Sorafenib via transforming growth factor-beta 1 in a SMAD dependent manner

Journal of Bioscience and Applied Research, 2019

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcrip... more MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcriptional interactions with mRNA. MiRNAs have recently considered as key regulators of various cancers including liver cancer. Sorafenib is one of the antitumor drugs for the treatment of advanced hepatocellular carcinoma. It acts as a multikinase inhibitor suppressing cell proliferation and angiogenesis. This study tries to investigate a potential microRNA-based mechanism of action of the drug by studying the effect of sorafenib on miR-23a and miR-24 levels in HCC cell lines HepG2 /Huh7 and revealing the possible drug mechanism against these oncogenic miRNAS in this study cell viability of cultured HepG2 /Huh7 after treatment with sorafenib were evaluated using Sulphorhodamine-B (SRB) assay, cell cycle and apoptosis estimated by flow cytometry assay. The caspase-3 level was determined using the ELISA assay. Moreover, miR-23a and miR-24 expressions levels analyzed by qPCR. Finally, TGF-β le...

Research paper thumbnail of Chemical composition, cytotoxicity and molecular profiling of Cordia africana Lam. on human breast cancer cell line

Natural Product Research, 2020

Metabolic profiling of the hexane extract and essential oil of Cordia africana Lam., an 9 economi... more Metabolic profiling of the hexane extract and essential oil of Cordia africana Lam., an 9 economically important agroforestry species, was analysed by GC-FID and GC-MS. 10 Cytotoxicity was assessed in MCF-7 cancer cells using sulphorhodamine-B assay. 11 Caspase-8, BcL-2 and Ki-67 levels were evaluated using enzyme-linked 12 immunosorbent assay. Forty-one compounds were identified in the hexane extract, 13 meanwhile, eighty compounds were annotated in the essential oil. n-Decane (9.52%), 14 -sitosterol (8.13%), undecane (6.32%) and palmitaldehyde (5.50 %) were the major 15 compounds identified in the hexane extract, whereas, -caryophyllene (32.0%), 16 germacrene D (10.12%) and δ-cadinene (7.20%) predominated in the essential oil. The 17 inhibitory concentrations (IC 50) of the extract and oil were 4.55 µg/mL and 12.90 18 µg/mL, respectively. Caspase-8 activity increased significantly in hexane extract 19 treated cells. Furthermore, BcL-2 and Ki-67 protein expression levels were 20 significantly decreased. Cordia africana Lam exhibits potent cytotoxicity against breast 21 cancer cell line, most likely through apoptosis regulation.

Research paper thumbnail of GC/MS Analysis and Molecular Profiling of Lemon Volatile Oil against Breast Cancer

Journal of Essential Oil Bearing Plants, 2019

Breast cancer is the most common among women cancers and the most likely to cause death. Citrus p... more Breast cancer is the most common among women cancers and the most likely to cause death. Citrus plants essential oils are reported for having potential cytotoxic activities. Thirty three and thirty five compounds were identified from leaves and green branches of Citrus limon (L.) Burm. family (Rutaceae), respectively. The main components were limonene (47.24 %; 55.23 %), geranial (14.48 %; 7.94 %) and neral (12.1 %; 6.1 %). Lemon leaf oil showed cytotoxic activity against breast carcinoma cells (MCF-7) at IC 50 of 10 % (v/v). A significant increase in the expression levels of the apoptotic protein caspase-8, a significant decrease in the expression levels of both the anti-apoptotic protein BcL-2 and the proliferative marker Ki-67 were observed (in comparison with un treated cells ; p<0.05). The docking results showed high affinity of geranial against caspase-8 and caspase-9 indicating the promising cytotoxic effect of lemon oil through enhancing apoptosis. Further studies are required to test the safety and toxicological properties of the oil as medicine.

Research paper thumbnail of MiRNAs-181a/b as Predictive biomarkers for olaparib sensitivity in triple-negative breast cancer cells

Biochemistry Letters, 2017

Triple negative breast cancer PARP, poly ADP-ribose polymerase ATM, ataxia telangiectasia mutated... more Triple negative breast cancer PARP, poly ADP-ribose polymerase ATM, ataxia telangiectasia mutated Background: spotting the scope on triple-negative breast cancer (TNBC) as the most aggressive type of breast cancer, with no targeted therapeutic options. TNBC is often characterized by having defects in DNA repair due to defects in BRCA making this cancer a rational target for the synthetic lethality of olaparib, as an inhibitory target agent of the alternative DNA repair pathway (poly ADP-ribose polymerase "PARP" inhibitor). Objectives: the present study aims to evaluate the value of miRNAs-181a/b as potential biomarkers in predicting the response of TNBC to olaparib. Methods: anti-miRNAs-181a/b was transfected into MDA-MB-231 cell line using HiPerFect transfection reagent, the transfected and untransfected cells were subjected to olaparib. The effect of miRNAs-181a/b on MDA-MB-231 treated cells with olaparib was evaluated through the detection of essential proteins involved in apoptosis and cell proliferation including Caspase-8, Bcl-2, and Ki-67. Further, the expression level of ataxia telangiectasia mutated (ATM) was determined as a functional target of miRNAs-181a/b. Results: a significant decrease in Caspase-8 activity, and Bcl-2, but a significant increase in cell survival, cell proliferation, and ATM protein were observed upon suppression of miRNAs-181a/b by their inhibitors followed by treatment with olaparib for TNBC cell line (MDA-MB-231 cells). Conclusions: our data confirmed that miRNA-181a and miRNA-181b play a critical role for detecting the sensitivity of TNBC cells to olaparib. As well as miRNAs-181a/b could be used as a potentially predictive biomarkers for response to olaparib.

Research paper thumbnail of Synthesis and biochemical studies of novel organic selenides with increased selectivity for hepatocellular carcinoma and breast adenocarcinoma

European Journal of Medicinal Chemistry, 2019

Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatoce... more Nineteen organoselenides were synthesized and tested for their intrinsic cytotoxicity in hepatocellular carcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines and their corresponding selective cytotoxicity (SI) was estimated using normal lung fibroblast (WI-38) cells. Most of the organic selenides exhibited good anticancer activity, and this was more pronounced in HepG2 cells. Interestingly, the napthoquinone-(5), thiazol-(12), and the azobased (13) organic selenides demonstrated promising SI (up to 76). Furthermore, the amine 4c, napthoquinone 5, and azo-based 13 and 15 organic selenides were able to down-regulate the expression of Bcl-2 and up-regulate the expression levels of IL-2, IL-6 and CD40 in HepG2 cells compared to untreated cells. Moreover, most of the synthesized candidates manifested good free radical-scavenging and GPx-like activities comparable to vitamin C and ebselen. The obtained results suggested that some of the presented organoselenium candidates have promising anti-HepG2 and antioxidant activities.

Research paper thumbnail of Crosstalk between liver-related microRNAs and Wnt/β-catenin pathway in hepatocellular carcinoma patients

Arab Journal of Gastroenterology, 2017

Background and study aims: Hepatocellular carcinoma (HCC) is one of the most common cancers world... more Background and study aims: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with highest incidence in Asia and Africa. MicroRNAs (miRNAs), a class of non-coding single stranded RNA, which not only post transcriptionally regulate gene expression but also respond to signaling molecules to affect cell functions such as Wnt/b-catenin signaling specifically in HCC. The goal of this study is to investigate the crosstalk between Wnt/b-catenin signaling proteins and microRNAs expression in HCC patients. Patients and methods: Fresh tissue samples of 30 primary HCC patients and 10 control subjects were included. Expression level of 13 different miRNAs (miR-10a-miR-106b-miR-99a-miR-148a-miR-125b-miR-30e-miR-183-miR-155-miR-199a-miR-199a3p-miR-24-miR-122 and miR-215) were examined using real-time PCR assay. Five proteins involved in the Wnt/b-catenin pathway (b-catenin, APC, c-myc, survivin and cyclin D1) were analysed by immunohistochemistry technique. The correlation between miRNAs expression levels with protein expressions was assessed. Results: Up-regulation of miR-155 and miR-183 was reported in HCC patients compared to normal controls and this up-regulation was significantly correlated with liver cirrhosis in the case of miR-155 (p < 0.05) referring to their oncogenic activity. Down-regulation was observed for 11 miRNAs in HCC indicating their tumour suppression activity. MiRNA-10a, miR-30e, miR-215, miR-125b and miR-148a were significantly correlated with the expression of important players in Wnt/b-catenin pathway including b-catenin, APC and c-myc (p < 0.05). Detailed analysis revealed that miR-215 is associated with the grade of the disease and miR-125b is associated with HCV infection. Conclusion: Collectively, our data showed potential role of miR-10a, miR-30e, miR-215, miR-125b and miR-148a as important mediators in HCC progression. Furthermore, their association with Wnt/ b-catenin cascade proteins could be exploited to develop new therapeutic target strategies in HCC.

Research paper thumbnail of Design, synthesis and screening of 1, 2, 4-triazinone derivatives as potential antitumor agents with apoptosis inducing activity on MCF-7 breast cancer cell line

European journal of medicinal chemistry, Jan 7, 2018

Some triazinone derivatives are designed and synthesized as potential antitumor agents. Triazinon... more Some triazinone derivatives are designed and synthesized as potential antitumor agents. Triazinone derivatives 4c, 5e and 7c show potent anticancer activity over MCF-7 breast cancer cells higher than podophyllotoxin (podo) by approximate 6-fold. DNA flow cytometry analysis for the compounds 3c, 4c, 5e, 6c and 7c show a potent inhibitory activity of cell proliferation and cell cycle arrest at G/M phase. Compounds 4c, 5e and 7c exhibit low to moderate β-tubulin polymerization inhibition percentage. Meanwhile, compound 6c displayed excellent β-tubulin percentage of polymerization inhibition equivalent to that exhibited by podo. In addition, compounds 4c, 5e and 7c show strong topoisomerase (topo) II inhibitory activity in nano-molar concentration, compared to known topo inhibitor as etoposide. Finally, apoptotic inducing activity over MCF-7 of compounds 4c, 5e, 6c and 7c is due to up-regulation of p53, increased Bax/Bcl-2 ratio and caspase3/7 levels 2-fold higher than podo.

Research paper thumbnail of Chemical composition of aqueous-ethanol extract of Luffa cylindrica leaves and its effect on representation of caspase 8, caspase 3 and the proliferation marker Ki67 in intrinsic molecular sub-types of breast cancer in vitro

Chemistry & biodiversity, Jan 6, 2018

Breast cancer constitutes the second most prevalent cancer in Egypt, the problem which needs more... more Breast cancer constitutes the second most prevalent cancer in Egypt, the problem which needs more trends in treatment and treatment development either by regimen modification or introducing new drugs, the main objective of this study is to screen the effects of the aqueous-ethanol herbal extract of Luffa cylindrica leaves on different types of breast cancer cell lines representing different molecular sub-types of the disease. The major active constituents of the extract were tentatively identified by LC/MS which revealed the presence of phenolic compounds derivatives and saponin that may responsible in part for the activity of the extract. The emphasis was laid on the main apoptotic pathways as well as the extract effect on the normal cell line. Results of phytochemical investigation, cell cycle analysis and molecular analysis of apoptotic and proliferative markers have shown effective anticancer activity against MCF-7, BT-474, and MDA-MB-231 cell lines which represent three sub-typ...

Research paper thumbnail of Combinatorial synthesis, in silico , molecular and biochemical studies of tetrazole-derived organic selenides with increased selectivity against hepatocellular carcinoma

European Journal of Medicinal Chemistry, 2016

Research paper thumbnail of Transforming growth factor‑β, insulin‑like growth factor I/insulin‑like growth factor I receptor and vascular endothelial growth factor‑A: Prognostic and predictive markers in triple‑negative and non‑triple‑negative breast cancer

Molecular medicine reports, Jan 27, 2015

In the current study, the prognostic and predictive values of serum transforming growth factor‑β1... more In the current study, the prognostic and predictive values of serum transforming growth factor‑β1 (TGF‑β1), insulin‑like growth factor I (IGF‑I)/IGF‑I receptor (IGF‑IR) and vascular endothelial growth factor‑A (VEGF‑A) were evaluated in triple‑negative and non‑triple‑negative breast cancer (TNBC and non‑TNBC). The aim was to identify a group of serological biomarkers and to identify possible candidates for targeted therapy in patients with TNBC and non‑TNBC. Protein levels of TGF‑β1, IGF‑I/IGF‑IR and VEGF‑A in the serum were measured in 43 TNBC, 53 non‑TNBC and 20 normal control participants using quantitative ELISA assays. Results were correlated against standard prognostic factors, response to treatment and survival. TNBC was identified to be associated with poor prognosis and serum levels of VEGF‑A and IGF/IGF‑IR were significantly higher in the TNBC group compared with the non‑TNBC group. IGF‑IR and VEGF‑A overexpression was observed to be correlated with TGF‑β1 expression and a...

Research paper thumbnail of siRNA Mediated-hTERT Knockdown Impedes Proliferation of Mammalian Cancer MCF7 and HepG2 Cells

Journal of American Science, 2011

Research paper thumbnail of Telomere length in chronic obstructive pulmonary disease

Egyptian Journal of Bronchology, 2015

Background Telomere length (TL) is considered a biomarker of cellular aging. Chronic obstructive ... more Background Telomere length (TL) is considered a biomarker of cellular aging. Chronic obstructive pulmonary disease (COPD) is found to be associated with premature aging and the senescence hypothesis is now accepted as a molecular pathway for COPD development. Purpose The aim of this study was to measure TL in COPD patients and to study its relation to demographic data, spirometric indices, and arterial blood gases parameters. Participants and methods We measured TL using quantitative PCR in 20 patients with severe to very severe COPD and 11 age-matched and sex-matched nonsmokers. Results TL was significantly shorter in COPD patients (P < 0.001). Among COPD patients, TL was significantly shorter in current smokers than ex-smokers. In COPD patients, TL was correlated positively with SpO2%, pH (P < 0.05), PaO2 (P < 0.01), FVC% (P < 0.05) and FEV1%, and FEF25–75% (P < 0.001) and not correlated with pack-year. The BODE (Body mass index, airflow Obstruction, Dyspnea, and Ex...

Research paper thumbnail of GC/MS Analysis and Molecular Profiling of Lemon Volatile Oil against Breast Cancer

Journal of Essential Oil Bearing Plants

Research paper thumbnail of Chemical composition, cytotoxicity and molecular profiling of Cordia africana Lam. on human breast cancer cell line

Research paper thumbnail of Induction of Anti-Proliferative and Apoptotic Effects of Sorafenib Using miR-27a Inhibitor in Hepatocellular Carcinoma Cell Lines

Asian Pacific Journal of Cancer Prevention

HCC patients received systemic chemotherapeutic agents (Liu et al., 2015). Sorafenib (Nexavar) is... more HCC patients received systemic chemotherapeutic agents (Liu et al., 2015). Sorafenib (Nexavar) is a multikinase inhibitor that targets both RAF and a number of tyrosine kinases, including vascular endothelial growth factor receptors (VEGFRs), and platelet-derived growth factor receptor-β (PDGFR-β) (Wilhelm et al., 2005). Despite the fact that sorafenib has been approved in several countries worldwide for advanced HCC patients still yet the drug show unsatisfied clinical outcomes due to its severe