Int J Biol Sci 2020; 16(8):1403-1416. doi:10.7150/ijbs.41768 This issue

Research Paper

Drp1-mediated mitochondrial fission contributes to baicalein-induced apoptosis and autophagy in lung cancer via activation of AMPK signaling pathway

Xiaohong Deng1, Jingjing Liu1, Lantao Liu2, Xianjun Sun1, Jianhua Huang1, Jingcheng Dong1✉

1. Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China
2. Department of Interventional Radiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200050, China

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Citation:
Deng X, Liu J, Liu L, Sun X, Huang J, Dong J. Drp1-mediated mitochondrial fission contributes to baicalein-induced apoptosis and autophagy in lung cancer via activation of AMPK signaling pathway. Int J Biol Sci 2020; 16(8):1403-1416. doi:10.7150/ijbs.41768. Available from https://www.ijbs.com/v16p1403.htm

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Abstract

Graphic abstract

Baicalein (BA), a natural compound extracted from Scutellaria baicalensis Georgi, has been reported to exert antitumor effect in various cancers. However, the underlying mechanisms have not been well demonstrated. In the present study, we focused on the relationship between mitochondrial fission and BA-induced apoptosis and autophagy. We showed that BA inhibited cell viability and induced mitochondrial apoptosis in A549 and H1299 lung cancer cells. BA induced the loss of mitochondrial membrane potential (MMP) and the release of cytochrome c and apoptosis inducing factor (Aif) from mitochondria to cytoplasm. Meanwhile, BA induced autophagy and activated autophagic flux. Furthermore, we found that BA induced mitochondrial fission and mitochondrial impairment. Blocking mitochondrial fission by mdivi-1 attenuated BA-induced apoptosis and autophagy. Moreover, BA activated AMP-activated protein kinase (AMPK) pathway. Knockdown of AMPK with lentivirus encoded AMPKα also attenuated BA-induced mitochondrial fission, apoptosis and autophagy. Our in vivo data confirmed that BA inhibited tumor growth and induced apoptosis and autophagy in a Lewis lung carcinoma (LLC) xenograft model via activation of AMPK/mitochondrial fission pathway. Our study highlights the critical role of AMPK/mitochondrial fission pathway in the regulation of BA-induced apoptosis and autophagy. These results revealed the molecular mechanism of the anti-lung cancer property of BA and provided novel perspectives for the application of BA in the treatment of lung cancer.

Keywords: baicalein, mitochondrial fission, apoptosis, autophagy, AMPK