6-Shogaol inhibits the cell motility of prostate cancer cells by suppressing the PI3K/AKT/mTOR and Ras/Raf/MAPK pathways with comparable effects to paclitaxel treatment

Abstract

Prostate cancer ranks among the top causes of cancer-related deaths in men, with a substantial number of fatalities occurring in metastatic cases. Although paclitaxel (PTX) is used as a first-line treatment, its effectiveness is hindered by side effects and drug resistance, which complicate the therapy and contribute to the progression of metastasis. Research has shown that phytochemicals can induce cancer cell death and inhibit metastasis without significantly harming normal cells, suggesting a potential alternative strategy for suppressing metastatic prostate cancer. 6-Shogaol (6-S), a pungent constituent of ginger, has been demonstrated to inhibit metastasis in renal cancer cells, human endometrial carcinoma, and lung and breast cancers by downregulating the PI3K/Akt/mTOR and Ras/Raf/MAPK pathways. However, the anti-metastatic effects of 6-S on prostate cancer remain unclear. Accordingly, this study was aimed at investigating how 6-S suppresses the metastatic capacity of human prostate cancer cells PC-3 and DU145. Results showed that 6-S inhibited cell migration and invasion in both cell lines in a dose-dependent manner, and no cytotoxicity was observed in the normal human prostate cell RWPE-1. Mechanistically, 6-S upregulated PTEN and suppressed the activation of the CXCL12/CXCR4, PI3K/AKT/mTOR, and Ras/Raf/MAPK pathways, which in turn affected the expression of transcription factors Snail and Twist, leading to increased E-cadherin levels and reduced expression of N-cadherin, vimentin, MMP-2, and MMP-9. This limited the cell motility and showed comparable effects to paclitaxel treatment. In summary, 6-S demonstrates significant potential against the metastatic characteristics of prostate cancer cells and could serve as a potential candidate for adjuvant therapy after further clinical evaluations.