Anti-proliferation and induction of mitochondria-mediated apoptosis by Garcinia hanburyi resin in colorectal cancer cells

Abstract

Introduction: Several parts of Garcinia hanburyi are used in traditional medicine for many purposes. In this study, Garcinia hanburyi resin (GHR) was explored for possible anti-proliferative effects and the underlying mechanism on colorectal cancer (CRC) cells. Methods: Gambogic acid (GA) content in GHR was analyzed by HPLC method. The cytotoxicities of GA and GHR were assessed in human CRC cell lines (SW480 and Caco-2) and normal colon cells (CCD841 CoN) using a trypan blue exclusion assay, MTS assay, and cell morphology analysis. Cell cycle and apoptosis at its half maximal inhibitory concentration (IC50) were analyzed using flow cytometry. And, the levels of intrinsic apoptosis-related proteins were measured by Western blot analysis. Results: GA was the major compound as 71.26% of the GHR. The cell viability of CRC cells was decreased in a time- and dose-dependent manner after exposure to GHR. The selectivity index indicated that GHR had a high degree of selectivity against CRC cells. The same result was obtained for GA treatment. In addition, GHR markedly induced typical apoptotic morphology of CRC cells, but had no obvious effect on normal colon cells. GHR induced apoptosis with the cell cycle arrest at the G2/M phase. An increase in Bax/Bcl-2 ratio and a decrease in procaspase-3 proteins indicated that GHR promoted apoptosis by disrupting the mitochondrial outer membrane permeability and the subsequent activation of caspase-3. Conclusion: GHR, which contained GA as an active compound, significantly inhibited CRC cell proliferation via the induction of intrinsic apoptosis, while having low toxicity on normal colon cells. Therefore, GHR could be proposed as a potent candidate for the treatment of CRC.

Keywords

• Garcinia hanburyi
• Gambogic acid
• Apoptosis
• Colorectal cancer