Genistein induces apoptosis in ovarian cancer cells via different molecular pathways depending on Breast Cancer Susceptibility gene-1 (BRCA1) status

Thasni, K. A.; Rojini, G; Rakesh, S; Ratheeshkumar, T.; Babu, Mani Shankar; Gopala, Srinivas; Banerji, Asoke; Srinivas, Priya

doi:10.1016/j.ejphar.2008.04.041

Cited by 25 publications

(18 citation statements)

References 26 publications

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“…GST has been reported to promote apoptosis via activation of casapse-8 in ovarian cancer cells [25]. Caspase-8-dependent cleavage of Bid to tBid provides a link between death receptor and mitochondria mediated pathways of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…1). SF (1, 2.5, and 5µM) and GST (25,50, and 100µM) were used as monotherapy whereas SF + GST were used as combination therapy for 24 h. Dose-dependently, treatments with SF, GST, and SF + GST decreased the cell viability in both SK-N-DZ and SH-SY5Y cell lines (Fig. 1a).…”

Section: Decease In Cell Viability Following Treatmentsmentioning

confidence: 98%

“…Cells (1×10 4 per well) were seeded in a flat-bottomed 96-well plate and incubated for 24 h at 37°C and in 5% CO 2 . Both cell lines were exposed to SF (1, 2.5, and 5µM for 24 h) and GST (25,50, and 100 μM for 24 h) either alone or in combination. The solvent DMSO treated cells served as control.…”

Section: Mtt Assaymentioning

confidence: 99%

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Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification

et al. 2009

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Neuroblastoma is an extracranial, solid, and heterogeneous malignancy in children. The conventional therapeutic modalities are mostly ineffective and thus new therapeutic strategies for malignant neuroblastoma are urgently warranted. We examined the synergistic efficacy of combination of sorafenib (SF) and genistein (GST) in human malignant neuroblastoma SK-N-DZ (N-Myc amplified) and SH-SY5Y (N-Myc non-amplified) cell lines. MTT assay showed dose-dependent decrease in cell viability and the combination therapy more prominently inhibited the cell proliferation in both cell lines than either treatment alone. Apoptosis was confirmed morphologically by Wright staining. Flow cytometric analysis of cell cycle phase distribution and Annexin V-FITC/PI staining showed increase in subG1 DNA content and early apoptosis, respectively, after treatment with the combination of drugs. Apoptosis was further confirmed by scanning electron microscopy. Combination therapy showed activation of caspase-8, cleavage of Bid to tBid, increase in p53 and p21 expression, down regulation of anti-apoptotic Mcl-1, and increase in Bax:Bcl-2 ratio to trigger apoptosis. Down regulation of MDR, hTERT, N-Myc, VEGF, FGF-2, NF-κB, p-Akt, and c-IAP2 indicated suppression of angiogenic and survival pathways. Mitochondrial release of cytochrome c and Smac into cytosol indicated involvement of mitochondia in apoptosis. Increases in proteolytic activities of calpain and caspase-3 were also confirmed. Our results suggested that combination of SF and GST inhibited angiogenic and survival factors and increased apoptosis via receptor and mitochondria mediated pathways in both neuroblastoma SK-N-DZ and SH-SY5Y cell lines. Thus, this combination of drugs could be a potential therapeutic strategy against human malignant neuroblastoma cells having N-Myc amplification or non-amplification.

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Section: Discussionmentioning

confidence: 99%

Section: Decease In Cell Viability Following Treatmentsmentioning

confidence: 98%

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Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification

et al. 2009

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“…As such, it will be necessary for future gene therapy approaches to be tailored to each patient's needs to activate specific tumor suppressor(s) and inhibit oncogenic signals based on patients' genetic profiling. Antisense/Ribozyme Apoptosis [191] BRAC-1/2 Tumor suppressor gene involved in transcriptional regulation of cell cycle Overexpressed Antisense Apoptosis [192] HER2/ neu (erbB-2)…”

Section: Current Treatment Strategiesmentioning

confidence: 99%

Addressing the Challenge: Current and Future Directions in Ovarian Cancer Therapy

Kaur¹,

Slavcev²,

Wettig

2009

CGT

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Numerous ovarian gene therapy strategies are in clinical phases based on concepts of replacement/ knock out of deregulated gene, suicide gene strategies, strengthening of the immune response against a tumor, inhibition of tumor angiogenesis and growth factors. Non-viral delivery systems have potential advantages over currently widely used viral vectors and other classical vectors for delivering therapeutic gene of interest. The present review provides a comprehensive overview of potential of various delivery systems currently in use. Non-viral formulations used in ovarian gene therapy include injecting naked DNA, liposomes, polyplexes, lipopolyplexes, nanoparticles, gene gun and ultrasound/microbubble mediated gene delivery. In addition to improving vector delivery, the DNA constructs need to be optimised for both efficient and long-term transgene expression. Minicircles using minimal immunological defined gene expression (MIDGE) technology, are a promising future alternative to plasmid for use in non-viral ovarian gene therapy in terms of biosafety, improved gene transfer, potential bioavailability, minimal size and little immune reaction. The review explores the best route of administration for ovarian cancer gene therapy given its peritoneal dissemination which poses a major challenge in treating ovarian cancer patients. Enhancement of therapeutic index can be further achieved by overcoming barriers both at cellular and nuclear levels. Selective tumor targeting with minimal toxicity using folate modified, incorporating nuclear localization signal and PEGylated stealth liposome's represents a popular approach and needs to be exploited in ovarian gene therapy.

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“…Bisphenol-A (BPA), dioxins, dichlorodiphenyltrichloroethane (DDT), alkylphenols, polychlorinated biphenyl (PCBs), and phthalates are well-known EDCs. Among these EDCs, phthalates are chemical compounds that are mainly used as plasticizers, stabilizers, dispersants and emulsifying agents in the manufacture of diverse industrial products (6,7). Di-n-butyl phthalate (DBP) is one of the main phthalates, together with di-(2-ethylhexyl) phthalate (DEHP) and benzyl butyl phthalate (BBP) and are often used as a plasticizer and solvent in personal care products including perfumes and hair spray (8,9).…”

Section: Introductionmentioning

confidence: 99%

Cell growth of BG-1 ovarian cancer cells is promoted by di-n-butyl phthalate and hexabromocyclododecane via upregulation of the cyclin D and cyclin-dependent kinase-4 genes

Hwang

Lee

et al. 2011

Mol Med Report

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Abstract. Endocrine-disrupting chemicals (EDCs) are environmentally persistent exogenous compounds released from various industrial products such as plastics, pesticides, drugs, detergents and cosmetics. They can cause a variety of adverse effects to the reproductive, developmental, immune and nervous systems in humans and wildlife. Di-n-butyl phthalate (DBP) is the main compound of phthalates and is reported to inhibit estrogen receptor (ER)-mediated gene expression and to interfere with normal fetal development of the male reproductive system. Hexabromocyclododecane (HBCD or HBCDD) is one of the brominated flame retardants (BFRs) which have been widely used in plastic, electronic and textile applications and are known to cause endocrine disruption with toxicity of the nervous system. In the present study, the estrogenic effects of DBP and HBCD were examined in an ovarian cancer cell line, BG-1, expressing high levels of ER via MTT assay and semi-quantitative reverse-transcription PCR. Treatment with DBP (10 -8 -10 -5 M) or HBCD (2x10 -8 -2x10 -6 M) resulted in increased cell proliferation of BG-1 cells as observed with 17-β estradiol (E2). In addition, both DBP and HBCD upregulated the expression levels of cell cycle-regulatory genes, such as cyclin D and cyclin-dependent kinase-4 (cdk-4), which are downstream target genes of ER, at 6 h after treatment. However, the expression of the p21 gene was not altered by DBP or HBCD at any time as with E2. Taken together, these results suggest that DBP and HBCD are EDCs which have apparent estrogenic activities by stimulating the cell proliferation of BG-1 cells and by inducing the expression of cyclin D and cdk-4. Our results suggest that DBP and HBCD have sufficient potency to disrupt the endocrine system and to stimulate cell growth in ER-positive cancer cells.

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Genistein induces apoptosis in ovarian cancer cells via different molecular pathways depending on Breast Cancer Susceptibility gene-1 (BRCA1) status

Cited by 25 publications

References 26 publications

Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification

Synergistic efficacy of sorafenib and genistein in growth inhibition by down regulating angiogenic and survival factors and increasing apoptosis through upregulation of p53 and p21 in malignant neuroblastoma cells having N-Myc amplification or non-amplification

Addressing the Challenge: Current and Future Directions in Ovarian Cancer Therapy

Cell growth of BG-1 ovarian cancer cells is promoted by di-n-butyl phthalate and hexabromocyclododecane via upregulation of the cyclin D and cyclin-dependent kinase-4 genes

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