Hernandezine, a novel AMPK activator induces autophagic cell death in drug-resistant cancers
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Betty Yuen Kwan Law1, Simon Wing Fai Mok1, Wai Kit Chan1, Su Wei Xu1, An Guo Wu1, Xiao Jun Yao1, Jing Rong Wang1, Liang Liu1, Vincent Kam Wai Wong1
1State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, China
Vincent Kam Wai Wong, e-mail: firstname.lastname@example.org
Liang Liu, e-mail: email@example.com
Keywords: hernandezine, AMPK activator, autophagy, autophagic cell death, drug-resistant cancer
Received: September 13, 2015 Accepted: January 01, 2016 Published: January 22, 2016
Drug resistance hinder most cancer chemotherapies and leads to disease recurrence and poor survival of patients. Resistance of cancer cells towards apoptosis is the major cause of these symptomatic behaviours. Here, we showed that isoquinoline alkaloids, including liensinine, isoliensinine, dauricine, cepharanthine and hernandezine, putatively induce cytotoxicity against a repertoire of cancer cell lines (HeLa, A549, MCF-7, PC3, HepG2, Hep3B and H1299). Proven by the use of apoptosis-resistant cellular models and autophagic assays, such isoquinoline alkaloid-induced cytotoxic effect involves energy- and autophagy-related gene 7 (Atg7)-dependent autophagy that resulted from direct activation of AMP activated protein kinase (AMPK). Hernandezine possess the highest efficacy in provoking such cell death when compared with other examined compounds. We confirmed that isoquinoline alkaloid is structurally varied from the existing direct AMPK activators. In conclusion, isoquinoline alkaloid is a new class of compound that induce autophagic cell death in drug-resistant fibroblasts or cancers by exhibiting its direct activation on AMPK.
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