Phloretin flavonoid exhibits selective antiproliferative activity in doxorubicin-resistant gastric cancer cells by inducing autophagy, inhibiting cell migration and invasion, cell cycle arrest and targeting ERK1/2 MAP pathway.

Studies have shown that Phloretin exerts anticancer effects on several types of cancer cells. Nonetheless, the anticancer effects of Phloretin have not been fully explored against the human gastric cancer cells. Therefore, this study was undertaken to evaluate the anticancer effects of Phloretin against the human gastric cancer cells.Cell proliferation was evaluated by WST-1 assay while cell cycle analysis was carried out by flow cytometry. The effects on cell migration and invasion were evaluated by wound healing assay and transwell assays, respectively. Electron microscopy and western blot methods were used to study effects on autophagy and ERK1/2/MAPK signalling pathway.The results showed that Phloretin inhibited the proliferation rate of the human SNU-1 gastric cancer cells and showed an IC50 of 18 µM. However, Phloretin showed very high IC50 (80 µM) against the normal GES-1 normal gastric cells. Electron microscopy showed that Phloretin triggered autophagy in the SNU-1 gastric cancer cells which was accompanied by enhancement in the expression of LC3B II and Beclin 1. Cell cycle analysis showed that Phloretin caused accumulation of the SNU-1 cells in the G0/G1 phase of the cell cycle triggering G0/G1 cell cycle arrest. The G0/G1 arrest of SNU-1 cells was also associated with depletion of cyclin D1 and D2 expression. Wound healing and transwell assays showed that Phloretin suppressed the migration of the SNU-1 gastric cancer cells, suggestive of the anti-metastatic potential of this molecule. Finally, this molecule also blocked the ERK1/2/MAPK signalling pathway in SNU-1 cells in a concentration-dependent manner.Phloretin may prove beneficial as a promising drug candidate for gastric cancer treatment provided further studies are carried out on it, especially toxicological studies.