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Gamabufotalin Induces Apoptosis and Cytoprotective Autophagy through the mTOR Signaling Pathway in Hepatocellular Carcinoma.
Liu, Ling; Shi, Dan; Xia, Zi-Yi; Wang, Bo-Wen; Wang, Xue-Li; Wang, Xiao-Ting; Wang, Guo-Li; Li, Min-Jing; Zheng, Qiu-Sheng; Li, Defang; Li, Bo-Han.
Affiliation
  • Liu L; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Shi D; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Xia ZY; The Second Medical College, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Wang BW; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Wang XL; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Wang XT; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Wang GL; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Li MJ; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Zheng QS; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Li D; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
  • Li BH; Featured Laboratory for Biosynthesis and Target Discovery of Active Components of Traditional Chinese Medicine, School of Integrated Traditional Chinese and Western Medicine, Binzhou Medical University, Yantai 264003 Shandong, PR China.
J Nat Prod ; 86(4): 966-978, 2023 04 28.
Article in En | MEDLINE | ID: mdl-37043698
ABSTRACT
Hepatocellular carcinoma (HCC) is a malignant tumor with a high rate of recurrence and a poor prognosis. Here, we investigated the effect and the potential antitumor mechanism of Gamabufotalin (CS-6) against HCC. Our results show that CS-6 strikingly reduced cell viability, inhibited colony formation, and promoted apoptosis in Hep3B and Huh7 cells. In vivo, CS-6 inhibited HCC xenograft tumor growth with no toxicity to normal tissues. Mechanistically, we found that CS-6 could induce cytoprotective autophagy through the mTOR-ULK1 signaling pathway through downregulation of p62 and upregulation of LC3 II/LC3 I. Meanwhile, CS-6 activated caspase-3 and PARP mediated apoptosis, and the caspase inhibitor Z-VAD-FMK blocked the CS-6-induced cell death in HCC cells. Moreover, autophagy and apoptosis were found to have antagonistic effects in Hep3B and Huh7 cells. Both the autophagy inhibitor chloroquine (CQ) and the mTOR activator MHY1485 blocked autophagy and further enhanced CS-6-induced apoptosis. Taken together, we demonstrated for the first time that CS-6 promotes apoptosis and cytoprotective autophagy through the mTOR signaling pathway in HCC, which proposes a novel strategy for HCC therapy.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Hepatocellular / Liver Neoplasms Limits: Humans Language: En Journal: J Nat Prod Year: 2023 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Carcinoma, Hepatocellular / Liver Neoplasms Limits: Humans Language: En Journal: J Nat Prod Year: 2023 Type: Article