In vitro metformin anti-neoplastic activity in epithelial ovarian cancer

Gotlieb, Walter H.; Saumet, Julio; Beauchamp, Marie‐Claude; Gu, Jing; Lau, Susie; Pollak, Michael; Bruchim, Ilan

doi:10.1016/j.ygyno.2008.04.008

Cited by 250 publications

(214 citation statements)

References 31 publications

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“…Controversy exists in the literature with respect to the interaction with cisplatin. According to the research conducted by Gotlieb et al (11) and Rattan et al (13), metformin with cisplatin synergistically killed ovarian cancer cells. In contrast, Janjetovic et al (18) reported an antagonistic interaction between metformin and cisplatin in human glioma, rat glioma, human neuroblastoma, mouse fibrosarcoma, and human leukemia cell lines, possibly via an AMP kinase-independent upregulation of the Akt survival pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Mazzone et al reported that diabetes patients with lung cancer who were previously treated with metformin or thiazolidinediones had a lower incidence of metastatic disease at the time of diagnosis and a reduced risk of death compared to those who did not receive the same treatment (4). Thereafter, the antiproliferative action of metformin was confirmed via in vivo and in vitro experiments in various cancer cell lines including breast (5)(6)(7)(8), prostate (9), pancreas (10), and ovarian cancer (11)(12)(13) as well as lung adenocarcinoma (8).…”

Section: Introductionmentioning

confidence: 99%

“…Despite these findings, the precise mechanisms of the metformin-induced effects are not fully understood. In particular, controversy remains about whether metformin is apoptotic (6,10) or just cytostatic (5,9) and whether it kills cancer cells synergistically with cytotoxic agents including cisplatin (11,13), paclitaxel (8), and doxorubicin (17), or if it is antagonistic to cisplatin (18,19).…”

Section: Introductionmentioning

confidence: 99%

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Antiproliferative action of metformin in human lung cancer cell lines

et al. 2012

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Abstract. The oral antidiabetic agent metformin has anticancer properties, probably via adenosine monophosphate-activated protein kinase activation. In the present study, growth inhibition was assessed by a clonogenic and by a cell survival assay, apoptosis induction was assessed by Hoechst staining and caspase activities and cell cycle alteration after exposure to metformin, and the interaction of metformin with cisplatin in vitro were elucidated in four human lung cancer cell lines representing squamous, adeno-, large cell and small cell carcinoma. Clonogenicity and cell proliferation were inhibited by metformin in all the cell lines examined. This inhibitory effect was not specific to cancer cells because it was also observed in a non-transformed human mesothelial cell line and in mouse fibroblast cell lines. Inhibition of clonogenicity was observed only when the cells were exposed to metformin for a long period, (10 days) and the surviving fraction, obtained after inhibiting proliferation by increasing the dose, reached a plateau at approximately 0.1-0.3, indicating the cytostatic characteristics of metformin. Metformin induced significant apoptosis only in the small cell carcinoma cell line. A tendency of cell cycle accumulation at the G0/G1 phase was observed in all four cell lines. Cisplatin, in a dose-dependent manner, severely antagonized the growth inhibitory effect of metformin, and even reversed the effect in three cell lines but not in the adenocarcinoma cell line. The present data obtained using various histological types of human lung cancer cell lines in vitro illustrate the cytostatic nature of metformin and its cytoprotective properties against cisplatin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Antiproliferative action of metformin in human lung cancer cell lines

et al. 2012

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“…Metformin had a suppressive effect on tumor growth in vitro. Isakovic et al [10] reported proliferation inhibition and apoptosis induction in glioma cell, similarly, the proliferation of prostate cancer cell lines [11] and ovarian cancer cell lines was inhibited after metformin treatment [12]. Breast cancer cell lines growth was also inhibited by metformin -Phoenix et al [13] reported growth inhibition of both estrogen re ceptor α negative (MDA-MB-231, MDA-MD-435) and positive (MCF-7, T47D) cell lines after metformin treatment.…”

mentioning

confidence: 98%

“…Metformin inhibited translation initiation in MCF-7 breast cancer cells, resulting in global protein synthesis decrease [14]. Inhibition of AMPK by compound C decreased antiproliferative properties of metformin on ovarian cancer cells [12] and glioma cells [10]. On the other hand, AMPK pathway inhibition (using siRNA against the two catalytic subunits of AMPK) did not prevent the antiproliferative effect of metformin in prostate cancer cell lines [11].…”

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confidence: 99%

Metformin in chemically-induced mammary carcinogenesis in rats

Bojková¹,

Orendáš²,

Garajová³

et al. 2009

neo

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In this paper the chemopreventive effect of peroral antidiabetic metformin in mammary carcinogenesis in female SpragueDawley rats was evaluated. Mammary carcinogenesis was induced by N-methyl-N-nitrosourea (NMU) administered in two intraperitoneal doses each per 50 mg/kg b.w. between 43.-55. postnatal days. Metformin was administered in drinking water (at a concentration of 50 µg/ml and 500 µg/ml) 13 days before the first NMU dose until the termination of the experiment. During the experiment the animals were weekly weighed and palpated for the presence of mammary tumors, the incidence, latency, tumor frequency, and tumor volume were recorded. The experiment was terminated 18 weeks after the first NMU dose, basic tumor growth parameters and metabolic and hormonal variables were evaluated. Metformin did not significantly alter the tumor growth although a delay in tumor onset was recorded after higher metformin dose. Metformin altered metabolic and hormonal variables. Insulinemia decreased after both metformin doses in comparison with intact rats without changes in glycemia, triacylglycerols concentration was decreased in liver and increased in serum when compared to intacts. Higher metformin dose attenuated lipoperoxidation in liver.

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Metformin and 4SC‐202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma

Tai

Deng

et al. 2019

Cancer Medicine

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Oral squamous cell carcinoma (OSCC) is the most common and aggressive epithelial tumor in the head and neck region with a rising incidence. Despite the advances in basic science and clinical research, the overall survival rate of OSCC remains low. Thus finding novel effective therapeutic agents for OSCC is necessary. In this study, we investigated the effects and mechanisms of combined metformin and 4SC‐202 in OSCC. Our results showed that metformin and 4SC‐202 synergistically suppressed the proliferation and promoted the intrinsic apoptosis of OSCC cells in vitro and in vivo. Importantly, the proteasome inhibitor MG132 impeded the ΔNp63‐decreasing effects after metformin and 4SC‐202 treatment, indicating that metformin and 4SC‐202 could promote the degradation of ΔNp63 protein. Moreover, ubiquitination level of ΔNp63 increased after metformin or/and 4SC‐202 administration. Furthermore, we revealed that ΔNp63 mediated anticancer effects of metformin and 4SC‐202, as overexpression or suppression of ΔNp63 could attenuate or facilitate the apoptosis rate of OSCC under metformin or/and 4SC‐202 treatment. Collectively, metformin and 4SC‐202 synergistically promote intrinsic apoptosis through accelerating ubiquitin‐mediated degradation of ΔNp63 in OSCC, and this co‐treatment can serve as a potential therapeutic scheme for OSCC.

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In vitro metformin anti-neoplastic activity in epithelial ovarian cancer

Cited by 250 publications

References 31 publications

Antiproliferative action of metformin in human lung cancer cell lines

Antiproliferative action of metformin in human lung cancer cell lines

Metformin in chemically-induced mammary carcinogenesis in rats

Metformin and 4SC‐202 synergistically promote intrinsic cell apoptosis by accelerating ΔNp63 ubiquitination and degradation in oral squamous cell carcinoma

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