Pholidonone, an active stilbene derivative from Pholidota cantonensis, exhibits pro-apoptotic effect via induction of endoplasmic reticulum stress in human gastric cancer

  • Liang Liu
  • Wei Wang
  • Zhichen Zhao
  • Chen Hu
  • Li Tao
  • Xianwen Zhang
DOI: https://doi.org/10.29219/fnr.v63.3553
Keywords: Pholidota cantonensis; pholidonone; ER stress-induced apoptosis; CHOP

Abstract

Abstract

Backgroud: Gastric cancer (GC) has become the second leading cause of death due to the worldwide incidence, mortality and prevalence. Therefore, it is urgent to find new drugs with low toxicity and high efficacy for the treatment of gastric cancer. Natural products as well as functional foods have always been the rich source of potential antitumor agents. Pholidota cantonensis Rolfe, a well-known functional food and a folk medicine, has been used for a long time in China for inflammatory diseases. Previously, we have evaluated its possible antitumor potentials by screening different solvent extracts, and found that the ethyl acetate (EtOAc) extract showed much higher cytotoxicity on human GC cell line AGS with IC50 value of 33.68 ± 1.68 μg/mL. In view of the poor knowledge concerning the phytochemical and pharmacological study of P. cantonensis, it is urgent to characterize the active compounds from EtOAc extract and the mechanisms of action underlying the anti-tumor effect of the herb.

Objective: This study aimed to identify the primary compounds in EtOAc extract of P. cantonensis involved in the antitumor activity of the plant by evaluating the cytotoxicity in two human GC cell lines including AGS and BGC-823 cells. Since endoplasmic reticulum (ER) stress-induced cell apoptosis represents attractive targets for cancer therapy recently, we focused on the underlying mechanisms associated with ER stress-induced cell apoptosis and related signaling pathways.

Methods: Various chromatographic techniques including silica gel, sephadex LH-20 and ODS C18 were used to separate the main active compound from EtOAc extract of P. cantonensis. The cell viability of AGS and BGC-823 cells upon purified compound treatment was determined by MTT assay. The alteration of cell morphology was observed using an inverted microscope. Cell apoptosis was determined by FITC-labeled annexin-V/PI double staining and flow cytometry analysis. Western blot analyses were performed to examine the levels of intracellular signaling molecules involved in ER stress-induced apoptosis.

Results: A rare stilbene derivative pholidonone was isolated and identified. The results showed that pholidonone displayed potent cytotoxicity on human gastric cancer cells. The IC50 values for 24 and 48 h in AGS cells were 26.54 ± 0.32 and 25.20 ± 3.67 μM, and the IC50 values for 24 and 48 h in BGC-823 cells were 32.41 ± 3.83 and 17.28 ± 2.30 μM, respectively). Additionally, pholidonone had pro-apoptotic effect on AGS and BGC-823 cells, and it dose-dependently up-regulated the levels of proteins involved in ER stress, including BiP, PDI, Calnexin, Ero1-Lα, IRE1α, PERK, CHOP and cleaved-caspase-3 in AGS and BGC-823 cells.

Conclusion: Pholidonone can trigger ER stress-induced apoptosis through PERK and IRE1α signaling pathway. Pholidonone might be a potential naturally occurred antitumor agent.

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Published
2019-09-06
How to Cite
Liu L., Wang W., Zhao Z., Hu C., Tao L., & Zhang X. (2019). Pholidonone, an active stilbene derivative from Pholidota cantonensis, exhibits pro-apoptotic effect via induction of endoplasmic reticulum stress in human gastric cancer. Food & Nutrition Research, 63. https://doi.org/10.29219/fnr.v63.3553
Issue
Vol 63 (2019)
Section
Original Articles

Authors retain copyright of their work, with first publication rights granted to SNF Swedish Nutrition Foundation. Read the full Copyright- and Licensing Statement.

 

 

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