Heterophyllin B ameliorates gastric cancer tumor growth through activating ER stress

Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Heterophyllin B (HB) has been proved to be a potential drug in cancer treatment.

In the current study, GC cells were treated with 0, 10, 25, or 50 μM of HB. Cell viability was determined by utilizing MTT assay. Flow cytometry was carried out for cell apoptosis and cell cycle analysis. The expression levels of IRE1, CHOP, GRP78 and Bcl-2 in cells and tumors were measured by Western blot and immunohistochemistry, respectively.

Our data uncovered that HB administration significantly suppressed GC cell viability, but facilitated GC cell apoptosis and cell cycle arrest at G0/G1 phase. The effects of HB on GC cell proliferation, apoptosis and cell cycle showed dosage-dependent manner. Furthermore, expression of ER stress-associated proteins like IRE1, CHOP and GRP78 was markedly upregulated, while anti-apoptosis protein Bcl2 expression was inhibited by HB treatment in a dosage-dependent manner. Our data indicated that HB treatment facilitated caspase-3 expression in a dose-dependent manner, but had no effect on caspase-8 expression. Importantly, the inhibition of HB to GC cell apoptosis and cell cycle process and the promotion of HB to GC cell proliferation were partly rescued by inhibition of ER stress utilizing 4-PBA. In animal experiments, HB administration suppressed GC tumor growth, boosted IRE1, CHOP and GRP78 expression and inhibited Bcl-2 expression.

All in all, HB treatment could effectively suppress GC cells proliferation and tumors growth and facilitate GC cells apoptosis and cell cycle arrest through activating ER stress. Our data indicated that HB may be a potential drug for GC treatment.