Overexpression of CYP11A1 recovers cell cycle distribution in renal cell carcinoma Caki-1

Background: Clear cell renal carcinoma is commonly known for its metastasis propensity to outspread to other organs and does not exhibit symptoms in the early stage. Recent studies have shown that deficiencies in CYP11A1 expression can lead to fatal adrenal failure if left untreated and are associated with downstream regulation in various cancer types. However, the molecular mechanisms of CYP11A1 and kidney cancer proliferation remain unclear. Methods: Normal and renal carcinoma cell lines (Hek293 and Caki-1) were transfected with CYP11A1 to stimulate overexpression. Cell cycle distribution was investigated using flow cytometry. Related signaling pathways were analysed by western blot. Results: We observed that overexpression of CYP11A1 suppressed the expression of cyclin B1 and cell-division cycle 2 but cyclin-dependent kinases 2 and 4 were not affected. Cancer cell migration and invasion were suppressed along with epithelial-intermediate metastatic markers snail and vimentin. In addition, CYP11A1 overexpressed Caki-1 cell line resulting in downregulation of cdc2/cyclinB1 while increasing phosphorylation of cdc25c, an upstream signal related to G2/M arrest. The markers for intrinsic-mitochondrial apoptosis pathway were not significantly altered. We also identified that the C-Raf/ERK/JNK/p38 pathway is an important mechanism for pro-apoptosis in CYP11A1 overexpressed cell-based models. Our results suggest that the disturbed cell cycle arrest distribution in renal cell carcinoma Caki-1 was recovered by the overexpression of CYP11A1 through G2/M arrest and C-Raf/ERK/JNK pathway. Conclusions: Our findings may suggest a promising new therapeutic target to suppress kidney cancer proliferation without affecting normal cells, thus could be used to improve cancer patients’ survival rate.