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Int J Biol Sci 2020; 16(1):74-84. doi:10.7150/ijbs.33787 This issue Cite

Research Paper

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

Bo Li1*, Pingting Zhou2*, Kehan Xu1*, Tianrui Chen1, Jian Jiao1, Haifeng Wei1, Xinghai Yang1, Wei Xu1✉, Wei Wan1✉, Jianru Xiao1

1. Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, Shanghai, China
2. Department of Radiation Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
* These authors have contributed equally to this work.

✉ Corresponding author: Department of Orthopedic Oncology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, China. (W. Xu; W. Wan; J. Xiao).

Citation:
Li B, Zhou P, Xu K, Chen T, Jiao J, Wei H, Yang X, Xu W, Wan W, Xiao J. Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma. Int J Biol Sci 2020; 16(1):74-84. doi:10.7150/ijbs.33787. https://www.ijbs.com/v16p0074.htm
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Abstract

Graphic abstract

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 in vivo. 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.

Keywords: Osteosarcoma, Metformin, Apoptosis, Autophagy, ROS, JNK

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APA
Li, B., Zhou, P., Xu, K., Chen, T., Jiao, J., Wei, H., Yang, X., Xu, W., Wan, W., Xiao, J. (2020). Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma. International Journal of Biological Sciences, 16(1), 74-84. https://doi.org/10.7150/ijbs.33787.

ACS
Li, B.; Zhou, P.; Xu, K.; Chen, T.; Jiao, J.; Wei, H.; Yang, X.; Xu, W.; Wan, W.; Xiao, J. Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma. Int. J. Biol. Sci. 2020, 16 (1), 74-84. DOI: 10.7150/ijbs.33787.

NLM
Li B, Zhou P, Xu K, Chen T, Jiao J, Wei H, Yang X, Xu W, Wan W, Xiao J. Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma. Int J Biol Sci 2020; 16(1):74-84. doi:10.7150/ijbs.33787. https://www.ijbs.com/v16p0074.htm

CSE
Li B, Zhou P, Xu K, Chen T, Jiao J, Wei H, Yang X, Xu W, Wan W, Xiao J. 2020. Metformin induces cell cycle arrest, apoptosis and autophagy through ROS/JNK signaling pathway in human osteosarcoma. Int J Biol Sci. 16(1):74-84.

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