Ilimaquinone induces apoptosis in gastric cancer cells by inhibiting the signal transducer and activator of the transcription 3 pathway

Abstract

Natural marine products possess pharmacological effects and have been a source of novel drugs for centuries. In this study, we explored the anti-tumor activity and underlying mechanism of action of ilimaquinone, a sesquiterpene quinone from marine sponges, in gastric cancer. Three gastric cancer cell lines (KATO III, SCM-1, and AZ521) were cultured. Cell viability, cell cycle, and apoptosis were determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay and flow cytometry. The levels of apoptotic proteins, proteins related to autophagy, and signal transducer and activator of transcription 3 (STAT3) were detected using western blotting. Transient transfection experiments were conducted to assess the expression of STAT3 in the gastric cancer cells. Ilimaquinone inhibited cell growth, caused cell cycle arrest in the S phase, and induced apoptosis. In addition, ilimaquinone modulates autophagy, and the viability of gastric cancer cells decreases upon exposure to a combination of the autophagic inhibitor, chloroquine. Notably, ilimaquinone downregulated the expression of p-STAT3 in a concentration- and time-dependent manner in both gastric cancer cell lines. Moreover, the compound-mediated inhibition of gastric cancer cell proliferation was restored by ectopic STAT3 expression. Collectively, these findings demonstrate the value of ilimaquinone in the treatment of gastric cancer.

Keywords: Apoptosis; Gastric cancer; Ilimaquinone; STAT3; Sponge.