Molecular medicine reports

Corosolic acid enhances 5-fluorouracil-induced apoptosis against SNU-620 human gastric carcinoma cells by inhibition of mammalian target of rapamycin.

PMID 26100106


5‑Fluorouracil (5‑FU), one of the oldest anticancer therapeutic agents, is increasingly being administered in cancer chemotherapy. In the present study, the anticancer effects of 5‑FU combined with corosolic acid (CRA) were determined in SNU‑620 human gastric carcinoma cells and the underlying mechanisms were examined. A combination treatment of 5‑FU and CRA inhibited the viability of cells additively. Furthermore, apoptotic activity following combination treatment was found to be stronger than that of the single treatments, as observed using an Annexin V/propidium iodide assay. The protein level of Bcl‑2 was decreased significantly by the combination treatment, whereas the protein level of Bim was increased. The release of mitochondrial cytochrome c was increased as a result of the combination treatment, however, the combination treatment additively increased caspase‑3 and poly‑(ADP‑ribose) polymerase cleavages. Additionally, the mammalian target of rapamycin (mTOR) signaling pathway, which is highly activated in gastric cancer, was regulated by 5‑FU and CRA, and additive mTOR/eukaryotic translation initiation factor 4E‑binding protein 1 (4‑EBP1) inhibition was observed with the combination treatment. Additional rapamycin treatment along with the combination treatment of 5‑FU and CRA showed a more marked inhibition of mTOR/4‑EBP1 in the cells, as well as increased apoptosis and antiproliferation. Thus, these data indicate that CRA enhances the anticancer activities of 5‑FU via mTOR inhibition in SNU‑620 human gastric carcinoma cells.