Centchroman mediated apoptosis involves cross-talk between extrinsic/intrinsic pathways and oxidative regulation

Nigam, Manisha; Singh, Neetu; Ranjan, Vishal; Zaidi, Deeba; Sharma, Rishi; Nigam, Deepti; Gupta, Dwijendra; Sundaram, Shanthy; Balapure, Anil K.

doi:10.1016/j.lfs.2010.10.015

Cited by 22 publications

(27 citation statements)

References 37 publications

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“…Molecular mechanistic studies with this compound have demonstrated that ormeloxifene induces caspase and mitochondrial-dependent apoptosis in breast cancer cells [5, 6]. In ER+ (MCF-7 cells) and ER− (MDA-MB231) breast cancer cell line models, ormeloxifene efficiently inhibited cell proliferation at concentrations similar to tamoxifene.…”

Section: Ormeloxifene As An Anti-cancer Agentmentioning

confidence: 99%

“…In ER+ (MCF-7 cells) and ER− (MDA-MB231) breast cancer cell line models, ormeloxifene efficiently inhibited cell proliferation at concentrations similar to tamoxifene. Ormeloxifene, however, was more effective against ER(+) MCF-7 cells than ER(−) MDA-MB231 [5–6] (Fig. 2).…”

Section: Ormeloxifene As An Anti-cancer Agentmentioning

confidence: 99%

“…Interestingly, ormeloxifene was also found to induce apoptosis at very low concentrations by depolarizing the mitochondrial membrane potential in the cell lines. In addition, ormeloxifene arrested breast cancer cells at the G0/G1 cell cycle phase [5, 6]. This effect correlated with the enhanced expression of cell cycle regulators like p21 Waf1/Cip1 and p27 Kip1 and down regulation of Cyclin-D1 and Cyclin-E expression [6].…”

Section: Ormeloxifene As An Anti-cancer Agentmentioning

confidence: 99%

“…Since p21 Waf1/Cip1 expression is usually controlled transcriptionally and post-transcriptionally by the p53-dependent/independent pathway [35], both cell types (MCF-7; p53+ and MDA-MB231; p53−) show p21 Waf1/Cip1 activation after ormeloxifene treatment leading to cell cycle arrest. Recently it has been reported that ormeloxifene mediated apoptosis involves a cross talk between the extrinsic/intrinsic pathways and the modulation of the redox system in breast cancer cells [5]. Additionally, the efficacy of ormeloxifene in combination with sensitizing agents such as cucurmin and resveratrol has also been investigated [36].…”

Section: Ormeloxifene As An Anti-cancer Agentmentioning

confidence: 99%

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Anti-Cancer Potential of a Novel SERM Ormeloxifene

Gara¹,

Sundram²,

Chauhan³

et al. 2013

CMC

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Ormeloxifene is a non-steroidal Selective Estrogen Receptor Modulator (SERM) that is used as an oral contraceptive. Recent studies have shown its potent anti-cancer activities in breast, head and neck, and chronic myeloid leukemia cells. Several in vivo and clinical studies have reported that ormeloxifene possesses an excellent therapeutic index and has been well-tolerated, without any haematological, biochemical or histopathological toxicity, even with chronic administration. A reasonably long period of time and an enormous financial commitment are required to develop a lead compound into a clinically approved anti-cancer drug. For these reasons and to circumvent these obstacles, ormeloxifene is a promising candidate on a fast track for the development or repurposing established drugs as anti-cancer agents for cancer treatment. The current review summarizes recent findings on ormeloxifene as an anti-cancer agent and future prospects of this clinically safe pharmacophore.

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Section: Ormeloxifene As An Anti-cancer Agentmentioning

confidence: 99%

Section: Ormeloxifene As An Anti-cancer Agentmentioning

confidence: 99%

Section: Ormeloxifene As An Anti-cancer Agentmentioning

confidence: 99%

Section: Ormeloxifene As An Anti-cancer Agentmentioning

confidence: 99%

See 2 more Smart Citations

Anti-Cancer Potential of a Novel SERM Ormeloxifene

Gara¹,

Sundram²,

Chauhan³

et al. 2013

CMC

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“…Our laboratory initially demonstrated its antineoplastic activity in vitro in MCF-7/MDA MB-231 cells through G0/G1 phase cell cycle arrest and caspase-dependent apoptosis. [567] It has also been found to be effective in patients of benign breast diseases such as mastalgia and fibroadenoma. [8] In head and neck cancer cells, it inhibits cellular proliferation by modulating PI3K/mTOR pathway.…”

mentioning

confidence: 99%

Genistein synergizes centchroman action in human breast cancer cells

et al. 2016

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Objectives:Despite the progress in the diagnosis and treatment of breast cancer, it remains a major health problem in women. Natural flavones along with chemotherapeutic agents enhance therapeutic response and minimize toxicity of chemical agents. Centchroman (CC) colloquially called as ormeloxifene, is a nonsteroidal oral contraceptive categorized as selective estrogen receptor modulator with anti-breast cancer activity. Genistein (GN), an isoflavone found mainly in soy products possesses anti-cancerous potential against a number of cancers including breast. The present study aims at investigating the combination of CC and GN in human breast cancer cell lines (HBCCs).Materials and Methods:Cytotoxic effect of CC and GN separately and in combination were assessed by sulforhodamine B (SRB) assay in MDA MB-231, MDA MB-468, MCF-7, T-47D HBCCs, and nontumorigenic human mammary epithelial cell (HMEC) MCF-10A. The drug interaction was analyzed using CompuSyn software through which combination index and dose reduction index were generated.Results:Combination of CC plus GN exerts significantly higher cytotoxicity compared to each drug per se in HBCCs, whereas HMEC-MCF-10A remains unaffected.Conclusion:On an overall basis, the drugs in combination enhanced cell killing in malignant cells. Therefore, the combination of CC with GN may offer a novel approach for the breast cancer.

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Nonhormonal selective estrogen receptor modulator 1‐(2‐[4‐{(3R,4S)‐7‐Methoxy‐2, 2‐dimethyl‐3‐phenyl‐chroman‐4yl}phenoxy]ethyl)pyrrolidine hydrochloride (ormeloxifene hydrochloride) for the treatment of breast cancer

Pillai

Regidi

Varghese

et al. 2018

Drug Development Research

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Breast cancer is the most common type of diagnosed cancers in women, difficult to treat, and has received international attention because of its aggressive nature and inherent drug resistance mechanisms. Development of a better selective estrogen receptor modulator with good therapeutic profile and less toxicity is very crucial in this scenario. This study was undertaken to evaluate and compare the in vitro and in vivo antitumor activities of ormeloxifene with other clinically used breast cancer drugs. Cytotoxic activity of ormeloxifene was compared with standard drugs, 4‐hydroxytamoxifene and Adriamycin. Ormeloxifene (50 μM) concentration showed cytotoxicity of 75% and 82% in MDAMB‐231 and 24% and 80% in MCF‐7 cells, respectively, after 72 and 144 hr of incubation as displayed by cell viability assay. The same concentration of ormeloxifene was shown to exert 74% caspase‐7 activation in MCF‐7 cells after 24 hr of incubation by fluorescence resonance energy transfer assay. Cell cycle analysis proved that there was an increase in sub‐G1 peak to 64.4% and 33.9% in MDAMB‐231 and MCF‐7 cells, respectively, after treatment using ormeloxifene (50 μM) for 48 hr. The nonobese diabetic‐severe combined immunodeficiency mice bearing tumor xenografts of triple negative MDAMB‐231 cells treated with ormeloxifene (3 mg/kg bw) showed significant regression in relative tumor volume compared to control. From the results obtained and as evidenced from prior literature, ormeloxifene in addition to contraceptive use, can be repositioned for the development of an efficacious anticancer drug. These data present the preclinical part of a well concerted effort to place ormeloxifene into further clinical trials.

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Centchroman mediated apoptosis involves cross-talk between extrinsic/intrinsic pathways and oxidative regulation

Cited by 22 publications

References 37 publications

Anti-Cancer Potential of a Novel SERM Ormeloxifene

Anti-Cancer Potential of a Novel SERM Ormeloxifene

Genistein synergizes centchroman action in human breast cancer cells

Nonhormonal selective estrogen receptor modulator 1‐(2‐[4‐{(3R,4S)‐7‐Methoxy‐2, 2‐dimethyl‐3‐phenyl‐chroman‐4yl}phenoxy]ethyl)pyrrolidine hydrochloride (ormeloxifene hydrochloride) for the treatment of breast cancer

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