PMID- 34114395 OWN - NLM STAT- MEDLINE DCOM- 20220202 LR - 20220202 IS - 2589-451X (Electronic) IS - 0255-2922 (Linking) VI - 41 IP - 3 DP - 2021 Jun TI - Celastrol induces caspase-dependent apoptosis of hepatocellular carcinoma cells by suppression of mammalian target of rapamycin. PG - 381-389 LID - 10.19852/j.cnki.jtcm.2021.03.006 [doi] AB - OBJECTIVE: To investigate the efficacy of celastrol treatment of hepatocellular carcinoma (HCC) cells in vitro and in vivo and to propose a mechanism of action. METHODS: A human HepG2 liver cancer cell line and a xenograft tumor model were used to investigate the effects of celastrol on HCC in vitro and in vivo. A CCK-8 kit was used to detect cell viability. Flow cytometry and terminal-deoxynucleoitidyl transferase mediated nick end labeling staining were used to detect apoptosis. Western blotting and immunohistochemistry were used to detect the expression of cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, cleaved-PARP, mammalian target of rapamycin (mTOR), and p-mTOR. Hematoxylin-eosin staining was used to observe the tissue morphology. RESULTS: Celastrol decreased the viability of HepG2 cells and induced apoptosis. Western blot assays indicated that celastrol up-regulated cleaved-caspase-3, cleaved-caspase-8, cleaved-caspase-9, and cleaved-PARP by inhibiting the phosphorylation of mTOR in HepG2 cells. Moreover, celastrol inhibited the tumor growth in a xenograft model. Celastrol also induced caspase-dependent apoptosis (up-regulation of cleaved-caspase- 3, -8, -9, and cleaved-PARP) and inhibited the activation of mTOR in vivo. CONCLUSION: Celastrol induces caspase-dependent apoptosis in HCC cells by inhibiting the activation of mTOR. FAU - Shen, Bo AU - Shen B AD - Nanjing Integrated Traditional Chinese and Western Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Nanjing 210014, China. FAU - Chen, Hai-Bin AU - Chen HB AD - Science and Technology Department, Nanjing University of Chinese Medicine, Nanjing 210023, China. FAU - Zhou, Hong-Guang AU - Zhou HG AD - The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China. FAU - Wu, Mian-Hua AU - Wu MH AD - The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - J Tradit Chin Med JT - Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan JID - 8211546 RN - 0 (Pentacyclic Triterpenes) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - L8GG98663L (celastrol) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Apoptosis MH - *Carcinoma, Hepatocellular/drug therapy/genetics MH - Cell Line MH - Cell Line, Tumor MH - Cell Proliferation MH - Humans MH - *Liver Neoplasms/drug therapy/genetics MH - Pentacyclic Triterpenes MH - Sirolimus MH - TOR Serine-Threonine Kinases/genetics OTO - NOTNLM OT - Apoptosi OT - Carcinoma, hepatocellular OT - Caspase OT - Celastrol OT - mTOR EDAT- 2021/06/12 06:00 MHDA- 2022/02/03 06:00 CRDT- 2021/06/11 07:16 PHST- 2021/06/11 07:16 [entrez] PHST- 2021/06/12 06:00 [pubmed] PHST- 2022/02/03 06:00 [medline] AID - 3160 [pii] AID - 10.19852/j.cnki.jtcm.2021.03.006 [doi] PST - ppublish SO - J Tradit Chin Med. 2021 Jun;41(3):381-389. doi: 10.19852/j.cnki.jtcm.2021.03.006.