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Title: The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells
Authors: Sun, H 
Huang, M
Yao, N
Hu, J
Li, Y
Chen, L
Hu, N
Ye, W
Tai, CSW 
Zhang, D
Chen, S 
Keywords: Akt
Autophagic degradation
Autophagic flux
Cathepsin B
Cycloartane triterpenoid
Multidrug-resistant HCC
Issue Date: 2017
Publisher: Elsevier Inc.
Source: Biochemical pharmacology, 2017, v. 146, p. 87-100 How to cite?
Journal: Biochemical pharmacology 
Abstract: Multidrug resistance is the main obstacle in cancer chemotherapy. Emerging evidence demonstrates the important role of autophagy in cancer cell resistance to chemotherapy. Therefore, autophagy inhibition by natural compounds may be a promising strategy for overcoming drug resistance in liver cancer cells. Here, we found that ADCX, a natural cycloartane triterpenoid extracted from the traditional Chinese medicine (TCM) source Cimicifugae rhizoma (Shengma), impaired autophagic degradation by suppressing lysosomal cathepsin B (CTSB) expression in multidrug-resistant liver cancer HepG2/ADM cells, thereby leading to autophagic flux inhibition. Moreover, impairing autophagic flux promoted ADCX-induced apoptotic cell death in HepG2/ADM cells. Interestingly, Akt was overactivated by ADCX treatment, which downregulated CTSB and inhibited autophagic flux. Together, our results provide the first demonstration that an active TCM constituent can overcome multidrug resistance in liver cancer cells via Akt-mediated inhibition of autophagic degradation.
ISSN: 0006-2952
EISSN: 1873-2968
DOI: 10.1016/j.bcp.2017.10.012
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