Inhibition of STAT3 signaling is associated with the anti-hepatocellular carcinoma effects of a triterpenoid-enriched extract from Antrodia camphorate mycelia

Joint Event on 12^th World Congress on Pharmaceutical Sciences and Innovations in Pharma Industry & 9^th Edition of International Conference on Alternative Medicine

February 26-28, 2018 London, UK

Peili Zhu, Junkui Li, Xiuqiong Fu, Ting Li, Hui Guo, Tao Su, Chenle Yin, Jiyao Chou, Yaping Wang and Zhiling Yu

Hong Kong Baptist University, Hongkong
Shenzhen Research Institute and Continuing Education - HKBU, China

Scientific Tracks Abstracts: Pharmacoeconomics

Abstract :

Hepatocellular carcinoma (HCC), the major form of primary liver cancers, is the third leading cause of cancer-related death worldwide. Signal transducer and activator of transcription 3 (STAT3) signalling is persistently activated in HCC and has been proposed as a molecular target for the treatment and prevention of HCC. Antrodia camphorata (AC), especially its triterpenoids, has been reported to have anti-HCC effects. Zhankuic acid A, a triterpenoid isolated from AC, exerts antiHCC effects by suppressing the activation/phosphorylation of JAK2 and STAT3 in HepG2 cells. In this study, we investigated the involvement of the STAT3 signaling pathway in the anti-HCC effects of a triterpenoid-enriched extract prepared from cultured AC mycelia (TEAC). HepG2, SMMC-7721 cell models and a SMMC-7721 xenografted mouse model were employed to evaluate the anti-HCC effects of TEAC. MTT assays showed that TEAC dose- and time-dependently inhibited the viability of HCC cells. TEAC also induced apoptosis in HepG2 and SMMC-7721 cells, which was confirmed by positive Annexin V/ PI double staining, and the cleavage of poly (ADP-ribose) polymerase (PARP), caspases 3, 8, and 9. Moreover, TEAC retarded migration and invasion of cultured HepG2 cells. Mechanistic studies revealed that TEAC decreased the protein expression levels of phospho-STAT3 and phospho-JAK2 (a cytoplasmic kinase of STAT3), as well as total STAT3 in human HCC cells. STAT3 mRNA expression levels and STAT3-luciferase reporter activity were also reduced by TEAC. STAT3 targeted genes BclxL and MMP2 were downregulated by TEAC. Overactivation of STAT3 diminished the cytotoxic effects of TEAC. In SMMC7721-bearing mice, intragastric administration of TEAC (100 mg/kg) for 15 days significantly suppressed tumor growth. These results indicated that TEAC exerted in vitro and in vivo anti-HCC effects and the STAT3 signalling pathway was involved in the effects. This study provides a pharmacological basis for developing TEAC as an anti-HCC agent.

Biography :

Peili Zhu is a PhD student in School of Chinese Medicine, Hong Kong Baptist University. She has specialization in Traditional Chinese Medicine. Her research interests are investigating the anti-cancer effects of traditional Chinese medicine and exploring the mechanism of action of these effects