Abstract
BACKGROUND: Resistance to docetaxel (DTX), a frontline chemotherapeutic agent for prostate cancer (PC), remains a major therapeutic challenge, often driven by impaired apoptosis and enhanced metastatic potential. Calebin A (CA), a natural polyphenol derived from turmeric, has demonstrated anticancer properties in various malignancies. This study investigated the individual and combined effects of CA and DTX on proliferation, apoptosis, cell cycle progression, migration, and gene expression in human PC3 prostate cancer cells. METHODS: PC3 cells were treated with varying concentrations of CA and DTX, alone or in combination. Cell viability was assessed using the MTT assay, and drug interactions were evaluated using the combination index (CI) analysis. Flow cytometry was employed to analyze apoptosis and cell cycle distribution. Gene expression of Bax, Bcl-2, MMP-2, and MMP-9 was quantified using qRT-PCR, while gelatin zymography and wound healing assays evaluated protease activity and migratory behavior, respectively. RESULTS: Both CA and DTX exhibited time- and dose-dependent cytotoxicity, with combination treatment producing synergistic effects (CI < 1). Co-treatment significantly increased apoptotic cell populations and induced marked sub-G1 and G2/M cell cycle arrest. The combination therapy upregulated the pro-apoptotic Bax/Bcl-2 ratio and downregulated MMP-2 expression, with modest reductions in MMP-2 and MMP-9 enzymatic activities. Furthermore, migratory capacity was significantly diminished under combinatorial treatment compared to monotherapies. CONCLUSION: CA enhances the antitumor efficacy of DTX by potentiating apoptosis, inhibiting migration, and modulating gene expression associated with metastasis and survival. These findings suggest CA as a promising adjuvant to overcome chemoresistance and improve therapeutic outcomes in prostate cancer.