J Cancer 2022; 13(12):3333-3341. doi:10.7150/jca.75791 This issue

Research Paper

Snake venom induces an autophagic cell death via activation of the JNK pathway in colorectal cancer cells

Ji Eun Yu, In Jun Yeo, Dong Won Lee, Ju Young Chang, Dong Ju Son, Jaesuk Yun, Sang-Bae Han, Jin Tae Hong

College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31, Osongsaengmyeong 1-ro, Osong-eup, Cheongju-si, Chungbuk 28160, Republic of Korea.

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Citation:
Yu JE, Yeo IJ, Lee DW, Chang JY, Son DJ, Yun J, Han SB, Hong JT. Snake venom induces an autophagic cell death via activation of the JNK pathway in colorectal cancer cells. J Cancer 2022; 13(12):3333-3341. doi:10.7150/jca.75791. Available from https://www.jcancer.org/v13p3333.htm

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Abstract

Graphic abstract

Snake venom contains many proteins that help treat or prevent thrombosis, cardiovascular disease, and cancer, and many studies have been reported in this regard. It has recently been reported that autophagy exerts anticancer effects by inducing tumor cell death and inhibiting cell growth. In this study, we investigated the effect of snake venom on autophagy. Unlike normal colon cells, LC3-II protein levels and LC3 puncta accumulation are increased in snake venom-treated colorectal cancer cells. Inhibition of autophagy by treating cells with hydroxychloroquine, an autophagy inhibitor, prevented snake venom-induced cell death, indicating that snake venom indeed induces autophagic cell death in human colorectal cancer cells. In addition, we demonstrated that activated JNK, and not mTOR signaling, is an upstream effector controlling autophagy. Pretreatment with SP600125, a JNK inhibitor, reversed snake venom-induced autophagy and cell death, indicating that JNK plays a critical role in snake venom-induced autophagy. This study demonstrated that snake venom can function as an anticarcinogenby induction autophagy.

Keywords: Snake venom, Autophagy, LC3, JNK