Compound C induces protective autophagy in human cholangiocarcinoma cells via Akt/mTOR‐independent pathway

• DOI: 10.1002/jcb.26723
• Publication Date: 2018-01-31T16:25:34Z
• Authors: Xiaofang Zhao; Guosong Luo; Ying Cheng; Wenjing Yu; Run Chen; Bin Xiao; Yuancai Xiang; Chunhong Feng; Wenguang Fu; Chunyan Duan; Fuli Yao; Xianming Xia; Qinghua Tao; Mei Wei; Rongyang Dai
• Keywords: 0303 health sciences; TOR Serine-Threonine Kinases; Apoptosis; 3. Good health; Cholangiocarcinoma; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Pyrimidines; Bile Duct Neoplasms; Autophagy; Tumor Cells, Cultured; Humans; Pyrazoles; Phosphorylation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Signal Transduction

Abstract Compound C, a well‐known inhibitor of AMP‐activated protein kinase (AMPK), has been reported to exert antitumor activities in some types cells. Whether compound C can effects human cholangiocarcinoma (CCA) remains unknown. Here, we demonstrated that is potent inducer cell death and autophagy CCA Autophagy inhibitors increased the cytotoxicity towards cells, as confirmed by LDH release, PARP cleavage. It notable treatment phosphorylated Akt, sustained high levels p70S6K, decreased mTOR regulated p‐ULK1 (ser757). Based on data blocking PI3K/Akt or had no apparent influence autophagic response, suggest induces independent Akt/mTOR signaling Further study inhibited phosphorylation JNK its target c‐Jun. Blocking SP600125 siRNA suppressed induction upon treatment. Moreover, induced p38 MAPK activation, inhibition promoted via activation. In addition, p53 expression, attenuated C‐induced response. Thus, triggers autophagy, at least part, pathways conclusion, suppresses could increase sensitivity CCA.