Capsaicin, the Pungent Component of Red Chili Pepper, induces p21-mediated Cell Cycle Arrest in Renal Cell Carcinoma via Downregulating GLI1: an Experimental Research <i>In Vitro</i>

Capsaicin is the pungent and bioactive compounds of <i>Capsicum annum.</i> Previous studies have demonstrated the potent anti-tumor effect of capsaicin on various human malignancies by experiments <i>in vitro</i> or <i>in vivo</i>. However, the mechanism underlying its antitumor efficiency is not fully elucidated. Cell cycle arrest is one of anti-proliferation mechanisms for anti-neoplastic drugs. The p21 protein, an important inhibitor of cell cycle progression, could block cyclin dependent kinases (CDKs) mediated activation of cyclins. As the downstream transcriptional factor of the Hh pathway, GLI1 plays a crucial role in cancer progression and prognosis evaluation. The aim of the present study is to explore the potential role of GLI1 in p21 mediated cell cycle arrest induced by capsaicin treatment in renal cell carcinoma (RCC) 786-O and Caki-1 cell lines. The results revealed that capsaicin could inhibit proliferation of RCC cells and cause G₀/G₁ cell cycle arrest <i>in vitro</i>. Besides, we discovered that the capsaicin treatment increased the expression of p21 protein and downregulated the expression of GLI1, suggesting that GLI1 was involved in the p21 mediated G₀/G₁ arrest induced by capsaicin administration in RCC 786-O and Caki-1 cell lines. In conclusion, our study demonstrated that capsaicin could induce p21 mediated cell cycle arrest via suppressing GLI1 to inhibit RCC cell proliferation, which might be a promising therapeutic strategy in RCC.