Pterostilbene Suppressed Cell Viability, Induced Apoptosis and Autophagy of Cisplatin-resistant Gastric Cancer Cells.

[BACKGROUND/AIM] Gastric cancer (GC) is one of the most common cancers worldwide. Cisplatin is a key therapeutic agent for treating GC. Currently, the resistance of GC cells to cisplatin remains a major concern. Pterostilbene (PTS) is a natural phytochemical found in blueberry and grape. The anti-cisplatin-resistant GC effects and pharmacological mechanisms of PTS are unknown.

[MATERIALS AND METHODS] We investigated the anticancer activity of PTS in cisplatin-resistant GC cells and explored its pharmacological mechanisms of action via cell viability assay, cell confluence assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, acridine orange (AO) staining, monodansylcadaverine (MDC) staining, caspase-9/-3 activity assay, and RNA sequencing (RNA-Seq) analysis.

[RESULTS] Our results showed that PTS inhibited cell viability and cell confluence of cisplatin-resistant GC cells using the CCK-8 assay and the IncuCyte S3 ZOOM System. The TUNEL assay showed that PTS promoted apoptosis in cisplatin-resistant GC cells. PTS induced apoptosis by increasing caspase-9 and caspase-3 activity. PTS promoted cell autophagy by increasing vacuole formation and acidic vesicular organelles using MDC and AO staining. We also observed an increase in the expression of LC3B in PTS-treated cisplatin-resistant GC cells. RNA-Seq analysis demonstrated that PTS induced apoptosis and autophagy in cisplatin-resistant GC cells by decreasing the expression of ATM/ATR, HIF-1, PI3K, RB1CC, TBK1, and mitochondria-related genes.

[CONCLUSION] Our results suggested that PTS is a promising phytochemical for GC therapy, particularly against cisplatin resistance.