Linda Einbond - Academia.edu (original) (raw)

Papers by Linda Einbond

Journal of Applied Polymer Science, 2018

ABSTRACTCurcumin is a widely researched and utilized natural product used for a variety of ailmen... more ABSTRACTCurcumin is a widely researched and utilized natural product used for a variety of ailments, including as a gastrointestinal aide and an anticancer agent. Curcumin, however, suffers from poor bioavailability. A strategy to circumvent poor bioavailability is to administer with an adjuvant or by synthetic modification. Herein, we demonstrate the incorporation of curcumin into a self‐degradable polymer by condensation with N,N′‐di‐Boc‐L‐cystine. The polymer is made self‐degradable upon deprotection of the cystine amines. Degradation is confirmed by thermogravimetric analysis and differential scanning calorimetry. Curcumin retains its anti‐cancer activity within the polymer showing activity against HT29 human colon cancer cells and DU‐145 prostate cancer cells. The self‐degrading polymer showed enhanced activity against HT29 cells compared to that of curcumin. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46867

Food and Chemical Toxicology, 2018

Previous studies indicate that the herb black cohosh (Actaea racemosa L.) and the triterpene glyc... more Previous studies indicate that the herb black cohosh (Actaea racemosa L.) and the triterpene glycoside actein inhibit the growth of human breast cancer cells and activate stress-associated responses. This study assessed the transcriptomic effects of black cohosh and actein on rat liver tissue, using Ingenuity and ToxFx analysis. Sprague-Dawley rats were treated with an extract of black cohosh enriched in triterpene glycosides (27%) for 24 hours or actein for 6 and 24 hours, at 35.7 mg/kg, and liver tissue collected for gene expression analysis. Ingenuity analysis indicates the top canonical pathways are, for black cohosh, RAR Activation, and, for actein, Superpathway of Cholesterol Biosynthesis, at 24 hours. Actein alters the expression of cholesterol biosynthetic genes, but does not inhibit HMG-CoA reductase activity. Black cohosh and actein inhibited the growth of human breast and colon cancer cells and synergized with the statin simvastatin. Combinations of black cohosh with certain classes of statins could enhance their activity, as well as toxic, such as inflammatory liver, side effects. Transcriptomic analysis indicates black cohosh and actein warrant further study to prevent and treat cancer and lipid disorders. This study lays the basis for an approach to characterize the mode of action and toxicity of herbal medicines. Highlights 3 Transcriptomic analysis of effects of black cohosh and actein on rat liver tissue: Ingenu ity Pathway and ToxFx analysis Black cohosh alters Acute Phase Response Signaling at 24 hours Actein alters the Superpathway of Cholesterol Biosynthesis at 6 and 24 hours Actein does not inhibit HMG-CoA reductase activity Black cohosh and actein inhibited the growth of colon cancer cells and synergized with the statin simvastatin.

Pharmacological research, Jan 3, 2018

The spice turmeric (Curcuma longa L.) has a long history of use as an anti-inflammatory agent. Th... more The spice turmeric (Curcuma longa L.) has a long history of use as an anti-inflammatory agent. The active component curcumin induces a variety of diverse biological effects and forms a series of degradation and metabolic products in vivo. Our hypothesis is that the field of toxicogenomics provides tools that can be used to characterize the mode of action and toxicity of turmeric components and to predict turmeric-drug interactions. Male Sprague-Dawley rats were treated for 4 days with turmeric root containing about 3% curcumin (comparable to what people consume in the fresh or dried root) or a fraction of turmeric enriched for curcumin (∼74%) and liver tissue collected for gene expression analysis. Two doses of each agent were added to the diet, corresponding to 540 and 2700 mg/kg body weight/day of turmeric. The transcriptomic effects of turmeric on rat liver tissue were examined using 3 programs, ToxFx Analysis Suite, in the context of a large drug database, Ingenuity Pathway and ...

Scientific Reports, 2016

Microvesicles (MVs) are lipid bilayer-covered cell fragments that range in diameter from 30 nm–1u... more Microvesicles (MVs) are lipid bilayer-covered cell fragments that range in diameter from 30 nm–1uM and are released from all cell types. An increasing number of studies reveal that MVs contain microRNA, mRNA and protein that can be detected in the extracellular space. In this study, we characterized induced pluripotent stem cell (iPSC) MV genesis, content and fusion to retinal progenitor cells (RPCs) in vitro. Nanoparticle tracking revealed that iPSCs released approximately 2200 MVs cell/hour in the first 12 hrs with an average diameter of 122 nm. Electron and light microscopic analysis of iPSCs showed MV release via lipid bilayer budding. The mRNA content of iPSC MVs was characterized and revealed the presence of the transcription factors Oct-3/4, Nanog, Klf4 and C-Myc. The protein content of iPSCs MVs, detected by immunogold electron microscopy, revealed the presence of the Oct-3/4 and Nanog. Isolated iPSC MVs were shown to fuse with RPCs in vitro at multiple points along the plas...

Fitoterapia, 2016

The cardiac glycoside digitoxin preferentially inhibits the growth of breast cancer cells and tar... more The cardiac glycoside digitoxin preferentially inhibits the growth of breast cancer cells and targets the Erk pathway. Digitoxin alters the expression of genes that mediate calcium metabolism and IAP genes. Since the optimal treatment for cancer involves the use of agents in combination, we assessed the growth inhibitory effects of digitoxin combined with agents that alter calcium metabolism, thapsigargin, a sarcoplasmic/ER Ca2+-ATPase inhibitor, and the statin simvastatin, as well as digitoxin&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s effect on the IAP pathway of apoptosis. To reveal signaling pathways, we treated human cancer cells with digitoxin, alone or combined with thapsigargin or simvastatin, and measured cell growth using the MTT and colony formation assays. We used histology and Western blot analysis of HEK293 cells to assay effects on IAPs. Digitoxin inhibited the growth of breast, colon and ovarian cancer cells. Consistent with an effect on calcium metabolism, digitoxin exhibited synergy with thapsigargin and simvastatin on ER-negative breast cancer cells. Digitoxin activates expression of Erk pathway genes and suppresses expression of IAP genes. The growth inhibitory effects on HEK293 cells are not blocked by the pancaspase inhibitor zVAD-FMK, indicating that digitoxin may act by a caspase independent pathway of apoptosis. Furthermore, digitoxin does not have an effect on XIAP protein, a major anti-apoptotic protein. Digitoxin appears to act through the Erk and stress response pathways and is worthwhile to study to prevent and treat cancer. Our findings warn of possible safety issues for cardiac patients who take a combination of digitoxin and statins.

Anticancer research

Previous studies indicate that specific extracts and the pure triterpene glycoside actein obtaine... more Previous studies indicate that specific extracts and the pure triterpene glycoside actein obtained from black cohosh inhibit growth of human breast cancer cells. Our aim is to identify alterations in gene expression induced by treatment with a methanolic extract (MeOH) of black cohosh. We treated MDA-MB-453 human breast cancer cells with the MeOH extract at 40 microg/ml and collected RNA at 6 and 24 h; we confirmed the microarray results with real-time RT-PCR for 18 genes. At 6 h after treatment there was significant increase in expression of ER stress (GRP78), apoptotic (GDF15), lipid biosynthetic (INSIG1 and HSD17B7) and Phase 1 (CYP1A1) genes and, at 24 h, decrease in expression of cell cycle (HELLS and PLK4) genes. Since the MeOH extract activated genes that enhance apoptosis and repressed cell cycle genes, it may be useful in the prevention and therapy of breast cancer.

Anticancer research, 2012

This study examines the chemopreventive potential and action of the herb black cohosh on Sprague-... more This study examines the chemopreventive potential and action of the herb black cohosh on Sprague-Dawley rats. Female Sprague-Dawley rats were treated with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 (Group I), 7.14 (Group II), 0.714 (Group III) or 0 mg/kg b.w. for 40 weeks starting from 56 weeks of age and the incidence of benign and malignant mammary tumors was determined at the end of observation. Among female rats treated at 35.7 and 7.14 mg/kg b.w. there was a dose-related reduction (p<0.05) of the incidence of mammary adenocarcinomas when compared to the treatment of 0.714 mg/kg b.w., with a protection index (calculated relative to the group III; PI=[total tumours × 100 animals of group III] - [total tumours × 100 animals of the group I (or group II)]/ [total tumours of group III] × 100) for mammary adenocarcinomas of 87.5 and 48.8%, respectively. Black cohosh reduced Ki-67 and cyclin D1 protein expression in fibroadenomas, by immunohistochemis...

Complementary and Alternative Therapies and the Aging Population, 2009

Publisher Summary The chapter reviews the chemopreventive and anticancer potential of the herb, b... more Publisher Summary The chapter reviews the chemopreventive and anticancer potential of the herb, black cohosh (Actaea racemosa). The extract and purified components of the herb is used for centuries for treatment of inflammation and various disorders in women including alleviation of the symptoms of menopause. From epidemiological studies, such menopausal treatment is correlated with reduction in risk of breast cancer. The herb contains major classes of secondary metabolites, triterpene glycosides, alkaloids and phenylpropanoids. Many studies have indicated that black cohosh can inhibit the growth of breast, prostate or skin cancer cells and therefore, the herb can be explored for developing cancer prevention or therapy. A summary of the chemopreventive and anticancer activities of black cohosh is given with precautions for its use. The effect of the extract of black cohosh for inhibiting the invasiveness of breast, prostate and oral cancers is elaborated as well as its action in combination with chemotherapy drugs. Some other properties of black cohosh is discussed which include anti-inflammatory, anti-oxidant and anti-HIV activities. The mode of action of black cohosh extract is explored and its role in induction of apoptosis and cell cycle.

Virology, 1974

Abstract The acid solubilization of the bacterial DNA after treatment with colicin E2 is reduced ... more Abstract The acid solubilization of the bacterial DNA after treatment with colicin E2 is reduced in cells carrying λ prophage. This effect appears to be due to the rex gene of the λ prophage.

Phytomedicine, 2008

The purpose of this report is to explore the growth inhibitory effect of extracts and compounds f... more The purpose of this report is to explore the growth inhibitory effect of extracts and compounds from black cohosh and related Cimicifuga species on human breast cancer cells and to determine the nature of the active components. Black cohosh fractions enriched for triterpene glycosides and purified components from black cohosh and related Asian species were tested for growth inhibition of the ER(-) Her2 overexpressing human breast cancer cell line MDA-MB-453. Growth inhibitory activity was assayed using the Coulter Counter, MTT and colony formation assays. Results suggested that the growth inhibitory activity of black cohosh extracts appears to be related to their triterpene glycoside composition. The most potent Cimicifuga component tested was 25-acetyl-7,8-didehydrocimigenol 3-O-beta-d-xylopyranoside, which has an acetyl group at position C-25. It had an IC(50) of 3.2microg/ml (5microM) compared to 7.2microg/ml (12.1microM) for the parent compound 7,8-didehydrocimigenol 3-O-beta-dxylopyranoside. Thus, the acetyl group at position C-25 enhances growth inhibitory activity. The purified triterpene glycoside actein (beta-d-xylopyranoside), with an IC(50) equal to 5.7microg/ml (8.4microM), exhibited activity comparable to cimigenol 3-O-beta-d-xyloside. MCF7 (ER(+)Her2 low) cells transfected for Her2 are more sensitive than the parental MCF7 cells to the growth inhibitory effects of actein from black cohosh, indicating that Her2 plays a role in the action of actein. The effect of actein on Her2 overexpressing MDA-MB-453 and MCF7 (ER(+)Her2 low) human breast cancer cells was examined by fluorescent microscopy. Treatment with actein altered the distribution of actin filaments and induced apoptosis in these cells. These findings, coupled with our previous evidence that treatment with the triterpene glycoside actein induced a stress response and apoptosis in human breast cancer cells, suggest that compounds from Cimicifuga species may be useful in the prevention and treatment of human breast cancer.

Journal of Natural Products, 2006

A new lignan, actaealactone (1), and a new phenylpropanoid ester derivative, cimicifugic acid G (... more A new lignan, actaealactone (1), and a new phenylpropanoid ester derivative, cimicifugic acid G (2), together with 15 known polyphenols, protocatechuic acid, protocatechualdehyde, p-coumaric acid, caffeic acid, methyl caffeate, ferulic acid, ferulate-1-methyl ester, isoferulic acid, 1-isoferuloyl-D-glucopyranoside, fukinolic acid, and cimicifugic acids A, B, and D-F, were isolated from an extract of the rhizomes and roots of black cohosh (Actaea racemosa). The structures of the new compounds were determined on the basis of NMR spectroscopic analysis. Compounds 1 and 2 displayed antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assay with IC 50 values of 26 and 37 µM, respectively. Other antioxidants identified from A. racemosa include cimicifugic acid A (3), cimicifugic acid B (4), and fukinolic acid (5). Compounds 1 and 2 also exhibited a small stimulating effect on the growth of MCF-7 breast cancer cell proliferation 1.24-fold (14 µM) and 1.14-fold (10 µM), respectively, compared to untreated cells.

Journal of Carcinogenesis, 2010

Background: Numerous studies have suggested that digitalis derivatives promise to be superior to ... more Background: Numerous studies have suggested that digitalis derivatives promise to be superior to existing adjuvant therapy for breast cancer as to effects and side-effects. In the present

International Journal of Cancer, 2007

Previous studies indicate that the triterpene glycoside actein from the herb black cohosh inhibit... more Previous studies indicate that the triterpene glycoside actein from the herb black cohosh inhibits growth of human breast cancer cells. This study seeks to identify genes altered in human breast cancer cells by treatment with actein, using gene expression analysis. We treated MDA-MB-453 human breast cancer cells with actein at 2 doses, 20 or 40 lg/mL, for 6 or 24 hr. We identified 5 genes that were activated after each of the treatments that are known to play a role in cellular responses to diverse stresses, including the DNA damage and unfolded protein responses. In addition, four genes that mediate the integrated stress response (ISR), including activating transcription factor 4, were induced under at least one of the 4 treatment conditions. We used hierarchical clustering to define clusters comprising patterns of gene expression. Two ISR genes, activating transcription factor 3 (ATF3) and DNA damage-inducible transcript 3, and lipid biosynthetic genes were activated after exposure to actein at 40 lg/ mL for 6 hr, whereas the cell cycle genes cyclin E2 and cell division cycle 25A were repressed. Our results suggest that actein induces 2 phases of the ISR, the survival phase and the apoptotic phase, depending on the dose and duration of treatment. We confirmed the results of gene expression analysis with real-time RT-PCR for 18 selected genes and Western blot analysis for ATF3. Since actein activated transcription factors that enhance apoptosis, and repressed cell cycle genes, it may be useful in the prevention and therapy of breast cancer.

Fundamental & Clinical Pharmacology, 2009

Native Americans have used the North American perennial black cohosh [Actaea racemosa L. syn. Cim... more Native Americans have used the North American perennial black cohosh [Actaea racemosa L. syn. Cimicifuga racemosa (L) Nutt] for centuries to treat a variety of conditions, including rheumatism, arthritis, muscle pain and dysmenorrhoea [1]. In recent years, it has become a popular alternative to hormone replacement therapy to alleviate menopausal symptoms. Recent studies indicate that black cohosh may have chemopreventive and anticancer potential [2,3]. The rhizomes and roots of the plant contain two major classes of secondary metabolites, triterpene glycosides and phenylpropanoids. Of the more than 42 triterpene glycosides present in black cohosh [4], the triterpene glycosides actein (Figure 1a) and 23-epi-26-deoxyactein [5] constitute about 6.4% of an n-butanolic fraction of black cohosh enriched for triterpene glycosides (27%).

Food Chemistry, 2004

The edible fruits of 12 plants were extracted in methanol and subjected to solvent-solvent partit... more The edible fruits of 12 plants were extracted in methanol and subjected to solvent-solvent partitioning to yield three fractions, hexane, ethyl acetate, and aqueous. The semi-purified aqueous fractions were separated over Diaion HP-20SS resin to remove sugars and ascorbic acid. These fractions were then screened for antioxidant activity using the 1,1-diphenyl-2-picrylhydrazyl assay. Nine of the semi-purified fractions exhibited high antioxidant capacity. Cyanidin-3-O-b-glucopyranoside, an anthocyanin antioxidant, was identified from semi-purified aqueous fractions of the tropical fruit star apple (Chrysophyllum cainito), Surinam cherry (Eugenia uniflora), and jaboticaba (Myrciaria cauliflora). Delphinidin-3-O-b-glucopyranoside was identified from E. uniflora.

Fitoterapia, 2012

Background: Studies indicate that extracts and purified components, including carnosic acid, from... more Background: Studies indicate that extracts and purified components, including carnosic acid, from the herb rosemary display significant growth inhibitory activity on a variety of cancers. Purpose: This paper examines the ability of rosemary/carnosic acid to inhibit the growth of human breast cancer cells and to synergize with curcumin. Materials and methods: To do this, we treated human breast cancer cells with rosemary/ carnosic acid and assessed effects on cell proliferation, cell cycle distribution, gene expression patterns, activity of the purified Na/K ATPase and combinations with curcumin. Results: Rosemary/carnosic acid potently inhibits proliferation of ER-negative human breast cancer cells and induces G1 cell cycle arrest. Further, carnosic acid is selective for MCF7 cells transfected for Her2, indicating that Her2 may function in its action. To reveal primary effects, we treated ER-negative breast cancer cells with carnosic acid for 6 h. At a low dose, 5 μg/ml (15 μM), carnosic acid activated the expression of 3 genes, induced through the presence of antioxidant response elements, including genes involved in glutathione biosynthesis (CYP4F3, GCLC) and transport (SLC7A11). At a higher dose, 20 μg/ml, carnosic acid activated the expression of antioxidant (AKR1C2, TNXRD1, HMOX1) and apoptosis (GDF15, PHLDA1, DDIT3) genes and suppressed the expression of inhibitor of transcription (ID3) and cell cycle (CDKN2C) genes. Carnosic acid exhibits synergy with turmeric/curcumin. These compounds inhibited the activity of the purified Na-K-ATPase which may contribute to this synergy. Conclusion: Rosemary/carnosic acid, alone or combined with curcumin, may be useful to prevent and treat ER-negative breast cancer.

Fitoterapia, 2013

The triterpene glycoside actein from the herb black cohosh preferentially inhibits the growth of ... more The triterpene glycoside actein from the herb black cohosh preferentially inhibits the growth of breast cancer cells and activates the ER stress response. The ER IP3 receptor and Na,K-ATPase form a signaling microdomain. Since actein is lipophilic, its action may be limited by bioavailability. To develop actein to prevent and treat cancer, we examined the primary targets and combinations with chemotherapy agents, as well as the ability of nanoparticles to enhance the activity. To reveal signaling pathways, we treated human breast and colon cancer, as well as 293T and 293T (NF-κB), cells with actein, and measured effects using the MTT, luciferase promoter, Western blot and histology assays. To assess effects on calcium release, we preloaded cells with the calcium sensitive dye Fura-2. To enhance bioavailability, we conjugated actein to nanoparticle liposomes. Actein strongly inhibited the growth of human breast cancer cells and induced a dose dependent release of calcium into the cytoplasm. The ER IP3 receptor antagonist heparin blocked this release, indicating that the receptor is required for activity. Heparin partially blocked the growth inhibitory effect, while the MEK inhibitor U0126 enhanced it. Consistent with this, actein synergized with the ER mobilizer thapsigargin. Further, actein preferentially inhibited the growth of 293T (NF-κB) cells. Nanoparticle liposomes increased the growth inhibitory activity of actein. Actein alters the activity of the ER IP3 receptor and Na,K-ATPase, induces calcium release and modulates the NF-κB and MEK pathways and may be worthwhile to explore to prevent and treat breast cancer.

Carbohydrate Research, 2011

The structures of three complex saponins from the fruit pods of Blighia sapida have been elucidat... more The structures of three complex saponins from the fruit pods of Blighia sapida have been elucidated and their 1H and 13 C NMR spectra assigned employing a variety of one-and twodimensional NMR techniques without degradative chemistry. The saponins have either four or six monosaccharide units linked to a triterpene aglycone. High-resolution, proton-coupled-HSQC spectra were important for determining both the identities of the intact monosaccharide units and coupling constants in strongly coupled proton spin systems. These NMR experiments will prove crucial as the complexity of saponin structures reaches the limit that can be determined solely by NMR.