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Cancer Cell International
Published in: Cancer Cell International 1/2014

Open Access 01-12-2014 | Primary research

Metformin impairs growth of endometrial cancer cells via cell cycle arrest and concomitant autophagy and apoptosis

Authors: Akimasa Takahashi, Fuminori Kimura, Akiyoshi Yamanaka, Akie Takebayashi, Nobuyuki Kita, Kentaro Takahashi, Takashi Murakami

Published in: Cancer Cell International | Issue 1/2014

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Abstract

Background

Effective therapies for early endometrial cancer usually involve surgical excision and consequent infertility Therefore, new treatment approaches that preserve fertility should be developed. Metformin, a well-tolerated anti-diabetic drug, can inhibit cancer cell growth. However, the mechanism of metformin action is not well understood. Here we investigate the roles of autophagy and apoptosis in the anti-cancer effects of metformin on endometrial cancer cells.

Methods

Ishikawa endometrial cancer cells were treated with metformin. WST-8 assays, colony formation assays, flow cytometry, caspase luminescence measurement, immunofluorescence, and western blots were used to assess the effects of metformin on cell viability, proliferation, cell cycle progression, apoptosis, and autophagy.

Results

Metformin-treated cells exhibited significantly lower viability and proliferation and significantly more cell cycle arrest in G1 and G2/M than control cells. These cells also exhibited significantly more apoptosis via both intrinsic and extrinsic pathways. In addition, metformin treatment induced autophagy. Inhibition of autophagy, either by Beclin1 knockdown or by 3-methyladenine-mediated inhibition of caspase-3/7, suppressed the anti-proliferative effects of metformin on endometrial cancer cells. These findings indicate that the anti-proliferative effects and apoptosis caused by metformin are partially or completely dependent on autophagy.

Conclusions

We showed that metformin suppresses endometrial cancer cell growth via cell cycle arrest and concomitant autophagy and apoptosis.
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Metadata
Title
Metformin impairs growth of endometrial cancer cells via cell cycle arrest and concomitant autophagy and apoptosis
Authors
Akimasa Takahashi
Fuminori Kimura
Akiyoshi Yamanaka
Akie Takebayashi
Nobuyuki Kita
Kentaro Takahashi
Takashi Murakami
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2014
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-14-53

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