Bakuchiol from Cullen corylifolium and its efficacy on apoptosis and autophagy in HepG2 cells

Bakuchiol (<b>4</b>), a component of <i>Cullen corylifolium</i>, has been reported to have estrogenic, antimicrobial, and anti-inflammatory activities. Nonetheless, its anticancer mechanisms and effectiveness against hepatocellular carcinoma remain unexplored. This study sought to elucidate the mechanism of apoptosis, autophagy, and cell cycle arrest caused by bakuchiol (<b>4</b>) and three flavonoids (<b>1</b>-<b>3</b>) with similar structures to compound <b>4</b> in hepatocellular carcinoma. Among the evaluated components (<b>1</b>-<b>4</b>), bakuchiol (<b>4</b>) exhibited a significant potential to induce apoptosis in HepG2 cells. This compound facilitates apoptotic processes by engaging both intrinsic and extrinsic signaling cascades, as evidenced by the enhanced ratios of Bax to Bcl-2 and tBid to Bid. In addition, bakuchiol (<b>4</b>) induced a dose-dependent cell cycle arrest, as assessed using a Tali^Ⓡ image-based cytometer. Since bakuchiol decreased CDK2 and CDK4, while increasing p53, p21, and p27, these data suggest that bakuchiol regulated early cell cycle progression. It also promotes the activity of AMPK and the LC3Ⅱ/LC3Ⅰ ratio, while suppressing Akt and mTOR. In conclusion, these results demonstrate that bakuchiol (4), a major component of <i>C. corylifolium,</i> has an anticancer effect in hepatocarcinoma cells by inducing both apoptosis and autophagy. This significant finding enlightens us about the <i>potential</i> of bakuchiol in cancer research, particularly in liver cancer treatment.