8-Shogaol from White Ginger induces cell apoptosis and autophagy in human colon cancer HCT116 cells and in vivo.

BACKGROUND

Colorectal cancer (CRC) constitutes a leading global health challenge, with incidence and mortality on an upward trajectory across diverse populations. Ginger (Zingiber officinale Roscoe) is a widely recognized traditional medicinal plant with established therapeutic and culinary applications. 8-Shogaol, a key phenolic component of ginger, exhibits diverse pharmacological activities including antitumor, anti-inflammatory, and analgesic effects. However, its specific mechanisms against colon cancer remain incompletely understood.

PURPOSE: Our study outlines the anti-cancer efficacy of 8-Shogaol against human colon cancer HCT116 cells and its underlying molecular mechanisms.

METHODS

miRNA-omics was employed to delineate the molecular mechanisms through which 8-Shogaol induces apoptosis in HCT116 cells. In vivo and in vitro validations were conducted by flow cytometry, Immunohistochemistry, and Western blotting for cell apoptosis and autophagy.

RESULTS

We identified 193 differentially expressed miRNAs (98 up-regulated, 95 down-regulated) among 1289 detected miRNAs, with KEGG pathway analysis revealing significant enrichment in the PI3K/AKT signaling pathway. In vivo experiments revealed that 8-Shogaol (40mg/kg) significantly suppressed tumor growth. In addition, 8-Shogaol induced cell cycle arrest exclusively at the G2/M phase and enhanced apoptotic effects in HCT116 cells by modulating key regulatory proteins (Bcl-2, Caspase 3, AKT, PI3K). 8-Shogaol also induced autophagy by regulating related proteins (LC3II/LC3I, ULK-1, Beclin-1). Mechanistic exploration suggested that 8-shogaol induced autophagy and apoptosis through inhibition of PI3K/AKT signaling pathway.

CONCLUSION

Our findings demonstrate that 8-Shogaol exerts potent anticancer effects against colon cancer through PI3K/AKT pathway modulation, concurrently inducing apoptosis and autophagy. This study provides comprehensive mechanistic insights into the therapeutic potential of 8-Shogaol for CRC treatment.