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Article

Sinensetin Induces Autophagic Cell Death through p53-Related AMPK/mTOR Signaling in Hepatocellular Carcinoma HepG2 Cells

1
Research Institute of Life science and College of Veterinary Medicine, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Korea
2
Biological Resources Research Group, Bioenvironmental Science & Toxicology Division, Gyeongnam Branch Institute, Korea Institute of Toxicology (KIT), 17 Jeigok-gil, Jinju 52834, Korea
3
Division of Life Sciences, Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Korea
4
College of Pharmacy, Yonsei University, Incheon 21983, Korea
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(8), 2462; https://doi.org/10.3390/nu12082462
Received: 24 April 2020 / Revised: 3 August 2020 / Accepted: 12 August 2020 / Published: 15 August 2020
(This article belongs to the Section Phytochemicals and Human Health)
Sinensetin (SIN) has been reported to exhibit anti-inflammatory and anti-cancer activity. However, the cellular and molecular mechanism by which SIN promotes hepatocellular carcinoma (HCC) cell death remains unclear. In the present study, we investigated the induction of cell death by SIN and its underlying mechanism in HepG2 cells, an HCC cell line. We found that SIN significantly induced cell death in HepG2 cells, whereas the proliferation rate of Thle2, human liver epithelial cells, was unaffected by SIN. SIN-treated HepG2 cells were not affected by apoptotic cell death; instead, autophagic cell death was induced through the p53-mediated AMPK/mTOR signaling pathway. Inhibition of p53 degradation led to both autophagy and apoptosis in HepG2 cells. p53 translocation led to SIN-induced autophagy, whereas p53 translocation inhibited SIN-induced apoptosis. However, SIN showed apoptosis in the p53-mutant Hep3B cell line. Molecular docking simulation of the p53 core domain showed effective binding with SIN, which was found significant compared with the known p53 activator, RITA. Collectively, these data suggest that SIN may be a potential anti-cancer agent targeting autophagic cell death in human liver cancer. View Full-Text
Keywords: sinensetin; autophagy; p53; AMPK; hepatocellular carcinoma sinensetin; autophagy; p53; AMPK; hepatocellular carcinoma
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MDPI and ACS Style

Kim, S.M.; Ha, S.E.; Lee, H.J.; Rampogu, S.; Vetrivel, P.; Kim, H.H.; Venkatarame Gowda Saralamma, V.; Lee, K.W.; Kim, G.S. Sinensetin Induces Autophagic Cell Death through p53-Related AMPK/mTOR Signaling in Hepatocellular Carcinoma HepG2 Cells. Nutrients 2020, 12, 2462. https://doi.org/10.3390/nu12082462

AMA Style

Kim SM, Ha SE, Lee HJ, Rampogu S, Vetrivel P, Kim HH, Venkatarame Gowda Saralamma V, Lee KW, Kim GS. Sinensetin Induces Autophagic Cell Death through p53-Related AMPK/mTOR Signaling in Hepatocellular Carcinoma HepG2 Cells. Nutrients. 2020; 12(8):2462. https://doi.org/10.3390/nu12082462

Chicago/Turabian Style

Kim, Seong Min, Sang Eun Ha, Ho Jeong Lee, Shailima Rampogu, Preethi Vetrivel, Hun Hwan Kim, Venu Venkatarame Gowda Saralamma, Keun Woo Lee, and Gon Sup Kim. 2020. "Sinensetin Induces Autophagic Cell Death through p53-Related AMPK/mTOR Signaling in Hepatocellular Carcinoma HepG2 Cells" Nutrients 12, no. 8: 2462. https://doi.org/10.3390/nu12082462

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