Metformin for lung cancer prevention and improved survival: a novel approach

Roos, Juliana F; Qudsi, Mariam; Samara, Arwa; Rahim, Madina M; Al-Bayedh, Samar A; Ahmed, Hafez

doi:10.1097/cej.0000000000000442

Cited by 7 publications

(4 citation statements)

References 54 publications

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“…While metformin alleviates cisplatin resistance in triple-negative breast cancer by facilitating RAD51 degradation [35], it has also been reported to promote cisplatin resistance in gastric cancer through PINK1/Parkin-mediated mitophagy [36]. Recent reports suggest that metformin improves the overall survival of lung cancer patients [37,38]. Although some previous studies suggest that the antineoplastic effect of metformin is closely related to mitochondrial function [39,40], it is still unclear p32/OPA1 contributes to cisplatin resistance 41 whether metformin sensitizes NSCLC to cisplatin by regulating mitochondrial dynamics.…”

Section: Discussionmentioning

confidence: 99%

p32/OPA1 axis-mediated mitochondrial dynamics contributes to cisplatin resistance in non-small cell lung cancer

Yu,

Peng,

Wang

et al. 2023

ABBS

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Cisplatin resistance is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). p32 and OPA1 are the key regulators of mitochondrial morphology and function. This study aims to investigate the role of the p32/OPA1 axis in cisplatin resistance in NSCLC and its underlying mechanism. The levels of p32 protein and mitochondrial fusion protein OPA1 are higher in cisplatin-resistant A549/DDP cells than in cisplatin-sensitive A549 cells, which facilitates mitochondrial fusion in A549/DDP cells. In addition, the expression of p32 and OPA1 protein is also upregulated in A549 cells during the development of cisplatin resistance. Moreover, p32 knockdown effectively downregulates the expression of OPA1, stimulates mitochondrial fission, decreases ATP generation and sensitizes A549/DDP cells to cisplatin-induced apoptosis. Furthermore, metformin significantly downregulates the expressions of p32 and OPA1 and induces mitochondrial fission and a decrease in ATP level in A549/DDP cells. The co-administration of metformin and cisplatin shows a significantly greater decrease in A549/DDP cell viability than cisplatin treatment alone. Moreover, D-erythro-Sphingosine, a potent p32 kinase activator, counteracts the metformin-induced downregulation of OPA1 and mitochondrial fission in A549/DDP cells. Taken together, these findings indicate that p32/OPA1 axis-mediated mitochondrial dynamics contributes to the acquired cisplatin resistance in NSCLC and that metformin resensitizes NSCLC to cisplatin, suggesting that targeting p32 and mitochondrial dynamics is an effective strategy for the prevention of cisplatin resistance.

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Section: Discussionmentioning

confidence: 99%

p32/OPA1 axis-mediated mitochondrial dynamics contributes to cisplatin resistance in non-small cell lung cancer

Yu,

Peng,

Wang

et al. 2023

ABBS

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“…According to the 2020 report, the incidence of lung cancer was 11.4% of all types of cancer [51]. It has been shown that metformin is also important in the prevention of lung cancer and in improving the survival of patients with lung cancer [56][57][58][59]. Many in vitro and in vivo studies indicate that metformin has a strong antitumour effect.…”

Section: Lung Cancermentioning

confidence: 99%

Metformin – a new approach

Cwynar-Zając¹

2021

pedm

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Metformin is a widely used biguanide drug recommended as a first-line antidiabetic for type 2 diabetes. Currently, metformin is used not only in the treatment of diabetes but also in other diseases. Some studies have shown that metformin causes weight loss in insulin-sensitive and insulin-resistant overweight and obese patients. Metformin is an effective and safe option for women with gestational diabetes and type 2 diabetes in pregnancy, and it may also increase the ovulation rate in patients with polycystic ovary syndrome (PCOS). Longer survival times have been observed in cancer patients using metformin. Metformin has been shown to significantly correlate with lower mortality in obese or type 2 diabetic women hospitalized for COVID-19. It also has a protective effect on the development and progression of many types of cancer. The mechanisms of action of metformin are complex and still not fully understood. Metformin has been shown to act through both AMP-activated protein kinase (AMPK)-dependent mechanisms and AMPK-independent mechanisms. This paper presents the benefits of using metformin in the treatment of various diseases.

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“…Consequently, many laboratories have tried to understand the mechanisms of action of metformin in different types of cancers, such as lung, prostate, and ovarian cancers or melanoma. The in vitro effects of metformin, alone or in combination with other drugs, have been studied in many different cancers ( 29 – 32 ). Moreover, numerous in vivo studies have demonstrated the efficacy of metformin in decreasing tumoral growth ( 33 , 34 ).…”

Section: Metformin Acts As An Anticancer Agentmentioning

confidence: 99%

Metformin: Focus on Melanoma

Jaune

Rocchi

2018

Front. Endocrinol.

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Metformin is the most common biguanide used in the treatment of diabetes, with 120 million treated patients worldwide. Metformin decreases hyperglycemia without inducing hypoglycemia in diabetic patients and is very well tolerated. The principal effects of metformin are to decrease hepatic gluconeogenesis and increase glucose absorption by skeletal muscles. These effects are primarily due to metformin's action on mitochondria, which requires the activation of metabolic checkpoint AMP-activated protein kinase (AMPK). AMPK is implicated in several pathways, and following metformin activation, it decreases protein synthesis and cell proliferation. Many studies have examined the role of metformin in the regulation of cancer cells, particularly its effects on cancer cell proliferation and cell death. Encouraging results have been obtained in different types of cancers, including prostate, breast, lung, and skin cancers (melanoma). Furthermore, many retrospective epidemiological studies in diabetes patients have shown that metformin treatment decreased the risk of cancers compared with other antidiabetic treatments. In this review, we will discuss the effects of metformin on melanoma cells. Together, our novel data demonstrate the importance of developing metformin and new biguanide-derived compounds as potential treatments against a number of different cancers, particularly melanoma.

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Metformin for lung cancer prevention and improved survival: a novel approach

Cited by 7 publications

References 54 publications

p32/OPA1 axis-mediated mitochondrial dynamics contributes to cisplatin resistance in non-small cell lung cancer

p32/OPA1 axis-mediated mitochondrial dynamics contributes to cisplatin resistance in non-small cell lung cancer

Metformin – a new approach

Metformin: Focus on Melanoma

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