Antitumor mechanism of combination of Angelica gigas and Torilis japonica in LNCaP prostate cancer cells via G1 arrest and inhibition of Wnt/beta-catenin and androgen receptor signaling

The goal of the current study is to assess the antitumor mechanism by the combination (7:3) of Angelica gigas arid Torilis japonica (AT) that was found most effective through screening against prostate-specific antigen (PSA) in LNCaP prostate cancer cells. Here, AT reduced the viability and the number of colonies in androgen-dependent LNCaP cells more than in androgen independent PC3 and DU145 cells. Also, AT induced G1 phase arrest, cleaved PARP and caspase 3, activated p27 and decreased the expression of Cyclin D1, Cyclin E, cdk2 in LNCaP cells. Furthermore, AT decreased the expression of PSA and androgen receptor (AR) at mRNA and protein levels in LNCaP cells. Interestingly, AT attenuated the expression of AR, PSA and Wnt-3a and the stability of AR and PSA in LNCaP cells. Furthermore, AT reversed dihydrotestosterone (DHT)-induced upregulation of AR and PSA in LnCaP cells. Notably, AT disrupted the protein-protein interaction, nuclear translocation and fluorescent expression of beta-catenin and AR in LNCaP cells. Consistently, beta-catenin depletion enhanced the decreased expression of AR in AT treated LNCaP cells. Taken together, our findings highlight evidence that AT suppresses the proliferation of LNCaP cells via G1 arrest and inhibition of beta-catenin and AR as a potential anticancer agent.

Automated summary

The combination of Angelica gigas and Torilis japonica (AT) was found to suppress the proliferation of LNCaP prostate cancer cells. AT exerts its anticancer effects by inducing G1 cell cycle arrest, downregulating key proteins, and inhibiting the activity of beta-catenin and AR.