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Hernandezine, a novel AMPK activator induces autophagic cell death in drug-resistant cancers.


ABSTRACT: 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.

SUBMITTER: Law BY 

PROVIDER: S-EPMC4884978 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Hernandezine, a novel AMPK activator induces autophagic cell death in drug-resistant cancers.

Law Betty Yuen Kwan BY   Mok Simon Wing Fai SW   Chan Wai Kit WK   Xu Su Wei SW   Wu An Guo AG   Yao Xiao Jun XJ   Wang Jing Rong JR   Liu Liang L   Wong Vincent Kam Wai VK  

Oncotarget 20160201 7


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 c  ...[more]

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