Cytotoxic and anti-tumor effects of 3,4-seco-lupane triterpenoids from the leaves of Eleutherococcus sessiliflorus against hepatocellular carcinoma

Abstract

A rich of 3,4-seco-lupane triterpenoids (3,4-SLT), including chiisanoside (CSS), divaroside (DVS), sessiloside-A1 (SSA), chiisanogenin (CSG), sessiligenin (SSG), were isolated from the ethanol extract of the leaves of Eleutherococcus sessiliflorus (LES). The present study was performed to explore the cytotoxic and anti-tumor effects of the isolated five ones, as well as potential molecular mechanisms. The results of a CCK-8 assay demonstrated that these 3,4-SLT can inhibit the growth of HepG2 cells, and SSG showed the most significant cytotoxicity. Hoechst 33258 fluorescence staining and Annexin V-FITC/PI staining indicated that 3,4-SLT in LES can induce HepG2 cell apoptosis effectively. The AutoDock Vina program was used to simulate molecular docking of drugs and targets to discuss possible pharmacological mechanisms. Besides, western blot and qRT-PCR results indicated that SSG can inhibit PI3K/AKT signaling pathway through controlling multi-targets. This study suggested that 3,4-SLT might become a new research hotspot for antineoplastic drugs.

Graphical Abstract

Keywords:

• Eleutherococcus sessiliflorus
• 3,4-seco-lupane triterpenoids
• anti-tumor
• molecule docking

Acknowledgements

The authors are grateful for the Institute of Translational Medicine, Bethune First Hospital, Jilin University.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work is supported by the Development Plan Project of Science and Technology Department of Jilin Province (Grant No. 20200404026YY), the Jiangsu Provincial Medical Youth Talent (Grant No. QNRC2016715), the Scientific Research Project of Jiangsu Provincial Bureau of Traditional Chinese Medicine (Grant No. YB201989) and the Clinical pharmacy Research Project of Wu Jieping Medical Foundation of Chinese Medical Association in 2018 (Grant Nos. 320.6750.19090-49 and LCYX-Q039).