Apoptosis‑Mediated Inhibition of Human Gastric Cancer Cell Proliferation by Cirsilineol

Background: Flavonoids constitute one of the best‑characterized groups of plant secondary metabolites with enormous pharmaceutical potential. A flavone type of plant flavonoid, cirsilineol, has been reported to exhibit proapoptotic effects against malignant human cells. Objectives: The present study was designed to investigate the antiproliferative effects of cirsilineol against human gastric cancer cells. Materials and Methods: Cell viability was assessed by 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) and colony formation assays. Apoptosis was detected by acridine orange/ ethidium bromide (AO/EB) and annexin V/propidium iodide (PI) assay. Protein expression was examined by western blotting analysis. Results: The results showed cirsilineol inhibits the proliferation of human gastric cancer cells. The IC50 of cirsilineol against human gastric cancer cells (BGC‑823, SGC‑7901, and MGC‑803) ranged from 8 to 10 µM. Nonetheless, cirsilineol exhibited comparatively lower antiproliferative effects against normal GES‑1 cells. The IC50 of cirsilineol against normal GES‑1 cells was found to be 120 µM. Colony formation assay showed that cirsilineol suppressed the colony formation of BGC‑823 and MGC‑803 cells in a dose‑dependent manner. Acridine orange and ethidium bromide (AO/EB) staining showed that cirsilineol induced apoptosis in BGC‑823 and MGC‑803 cells. The percentage of apoptosis increased from 7.4% in control to 40.5% in BGC‑823 cells and from 6.56% in control to 33.53% in MGC‑803 cells at 8 µM cirsilineol. Western blotting showed cirsilineol caused an increase in Bax and cleaved caspase‑3 and a decrease in Bcl‑2 expression in both BGC‑823 and MGC‑803 cells. Conclusion: Together, the results are indicative of the proapoptotic and antitumor potential of cirsilineol against gastric cancer cells, suggestive of its possible therapeutic significance in future.