Dimethyl cardamonin induces G2/M-phase cell cycle arrest, apoptosis and autophagy in HCT116 cells

Abstract

Dimethyl cardamonin (2’,4’-dihydroxy-6’-methoxy -3’,5’-dimethylchalcone; DMC) is a naturally occurring chalcone, and it is the major compound isolated from the leaves of Syzygium samarangense (Blume) Merr. & L.M. Perry (Myrtaceae). Experiments were conducted to determine the effects of a DMC on cell proliferation, cell-cycle distribution and programmed cell death in cultures of human HCT116 colorectal carcinoma cells. In this study, the effect of a DMC on the proliferation and autophagy of cultured HCT116 was elucidated. Results showed that DMC inhibited HCT116 cell proliferation and induced G2/M cell cycle arrest which was associated with the conversion of microtubule associated protein light chain 3 (LC3)-I to LC3-II, an autophagosome marker, and the incorporation of monodansylcadaverine (MDC), a marker for the acidic compartment of autolysosomes acidic vesicular organelles. Combination of DMC with an autophagy inhibitor, such as 3-methyladenine (3-MA), beclin 1 siRNA or ATG5 siRNA, suppressed the effect of DMC-mediated cell death. These results imply that DMC can suppress HCT116 colorectal carcinoma cells proliferation through G2/M phase cell-cycle delay, and can induce autophagy, the hallmark of Type II programmed cell death (PCD). Taken together, our results suggest that DMC may be an effective chemotherapeutic agent for colorectal carcinoma.