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Review
. 2019 Aug 22;5(8):FSO410.
doi: 10.2144/fsoa-2019-0053.

Anticancer activity of metformin: a systematic review of the literature

Mohamad Aljofan  1 , Dieter Riethmacher  1
Affiliations
Review

Anticancer activity of metformin: a systematic review of the literature

Mohamad Aljofan et al. Future Sci OA. .

Abstract

Background: The anticancer activity of metformin has been confirmed against several cancer types in vitro and in vivo. However, the underlying mechanisms of metformin in the treatment of cancer are not fully understood. This systematic review aims to discuss the possible anticancer mechanism of action of metformin.

Method: A search through different databases was conducted, including Medline and EMBASE.

Results: A total of 96 articles were identified of which 56 were removed for duplication and 24 were excluded after reviewing the title and abstract. A total of 12 research articles were included that describe different antiproliferative mechanisms that may contribute to the antineoplastic effects of metformin.

Conclusion: This analysis discussed the potential anticancer activity of metformin and highlighted the importance of AMPK as a potential target for anticancer therapy.

Keywords: AMPK; anticancer; cancer; mechanism of action; metformin.

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Conflict of interest statement

Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. Flow of the information searched through the current systematic review.
The different stages of search for the current systematic review. The initial search yielded 96 articles based on their titles, but the majority were excluded after reviewing the abstract. The remainder were screened and only 12 articles were included in the review.
Figure 2.
Figure 2.. Potential antiproliferative mechanisms of metformin.
Metformin’s potential activation of the apoptotic pathway. It is thought that metformin inhibits tumor growth and progression via activation of apoptosis. For instance, it was claimed that metformin enhances apoptosis by targeting AMPK and AKT/mTOR pathways. It was also reported that metformin activates Stat3 through an mTOR independent manner as well as via an AMPK/mTOR dependent way.
Figure 3.
Figure 3.. The effect of glucose environment on metformin’s antiproliferative activity.
The effect of glucose levels of low/normal on the antiproliferative activity of metformin. Some reports have suggested that glucose starvation increases ROS production that triggers ER stress induced apoptosis through ROS/ASK1/JNK pathway or via Bcl-2 signaling, which is thought to enhance metformin’s antiproliferative activity. To the contrary, others reported that low glucose may hinder metformin’s antiproliferative activity and that treatment with metformin significantly reduced the expression level of the proliferation marker Ki-67 in normal glucose, but the opposite was observed with in glucose environment. ER: Endoplasmic reticulum; ROS: Reactive oxygen species.
See this image and copyright information in PMC

References

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