Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma

Metformin, an ancient drug commonly used for treating type II diabetes, has been associated to anti-cancer capacity in a variety of developing cancers, though the mechanism remains elusive. Here, we aimed to examine the inhibitory effect of metformin in osteosarcoma. Herein, we demonstrated that met...

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Bibliographic Details
Published in:International journal of biological sciences 2020, Vol.16 (1), p.74-84
Main Authors: Li, Bo, Zhou, Pingting, Xu, Kehan, Chen, Tianrui, Jiao, Jian, Wei, Haifeng, Yang, Xinghai, Xu, Wei, Wan, Wei, Xiao, Jianru
Format: Article
Language:English
Subjects:
Antibodies
Antitumor activity
Apoptosis
Autophagy
Biomedical materials
Bone cancer
c-Jun protein
Cancer therapies
Cell cycle
Cell death
Cell growth
Cyclin-dependent kinases
Diabetes mellitus
Flow cytometry
Kinases
Metformin
Morphology
Osteosarcoma
Phagocytosis
Research Paper
Signal transduction
Signaling
Transcription factors
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Summary:Metformin, an ancient drug commonly used for treating type II diabetes, has been associated to anti-cancer capacity in a variety of developing cancers, though the mechanism remains elusive. Here, we aimed to examine the inhibitory effect of metformin in osteosarcoma. Herein, we demonstrated that metformin treatment blocked proliferation progression by causing accumulation of G2/M phase in U2OS and 143B cells. Furthermore, metformin treatment triggered programmed cell death process in osteosarcoma cell lines. Further research indicated the induction of apoptosis and autophagy triggered by metformin could remarkably attenuate after the treatment of ROS scavenger NAC and JNK inhibitor SP600125. Additionally, our results showed that NAC-suppressed JNK/c-Jun signaling pathway could have been activated through metformin treatment. Lastly, metformin could inhibit osteosarcoma growth under safe dose . Thus, we propose that metformin could induce cell cycle arrest as well as programmed cell death, including apoptosis and autophagy, through ROS-dependent JNK/c-Jun cascade in human osteosarcoma. This metformin-induced pathway provides further insights into its antitumor potential molecular mechanism and illuminates potential cancer targets for osteosarcoma.
ISSN:1449-2288
1449-2288
DOI:10.7150/ijbs.33787