TY - JOUR
T1 - The cycloartane triterpenoid ADCX impairs autophagic degradation through Akt overactivation and promotes apoptotic cell death in multidrug-resistant HepG2/ADM cells
AU - Sun, Haiyan
AU - Huang, Maohua
AU - Yao, Nan
AU - Hu, Jianyang
AU - Li, Yingjie
AU - Chen, Liping
AU - Hu, Nan
AU - Ye, Wencai
AU - Chi-Shing Tai, William
AU - Zhang, Dongmei
AU - Chen, Sibao
N1 - Funding Information:
The work was co-supported by National Natural Science Foundation (Grant number: 81373953), Guangdong Province Natural Science Foundation (Grant number: S2013050014183), Basic Research Foundation of Shenzhen Science and Technology Innovation Committee (JCYJ20151030164022389) and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (Grant number: GDHVPS2016).
Funding Information:
The work was co-supported by National Natural Science Foundation (Grant number: 81373953 ), Guangdong Province Natural Science Foundation (Grant number: S2013050014183 ), Basic Research Foundation of Shenzhen Science and Technology Innovation Committee ( JCYJ20151030164022389 ) and Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (Grant number: GDHVPS2016 ).
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/12/15
Y1 - 2017/12/15
N2 - 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.
AB - 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.
KW - Akt
KW - Autophagic degradation
KW - Autophagic flux
KW - Cathepsin B
KW - Cycloartane triterpenoid
KW - Multidrug-resistant HCC
UR - http://www.scopus.com/inward/record.url?scp=85033663630&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2017.10.012
DO - 10.1016/j.bcp.2017.10.012
M3 - Journal article
C2 - 29074104
AN - SCOPUS:85033663630
SN - 0006-2952
VL - 146
SP - 87
EP - 100
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
ER -
