Vitamin B12 Enhances Cisplatin Efficacy via Apoptosis and MAPK/ERK1-2, P38, PARP-1 Modulation in Prostate Cancer

INTRODUCTION: Prostate cancer (PC) is the most common malignancy among men and remains a major cause of cancer-related mortality worldwide. Cisplatin is a widely used chemotherapeutic agent in cancer treatment. Vitamin B12 has been shown to play a role in enhancing the efficacy of certain cancer drugs when used in combination therapies. This study investigates the antitumor effects and mechanisms of action of B12 and Cisplatin combination therapy in prostate cancer cells.
METHODS: The clonogenic assay was used to determine the fraction of surviving cells after treatment. The MTS assay and flow cytometry were performed to assess the impact of B12 and Cisplatin on cell proliferation and apoptosis, while Western blot analysis was used to examine the expression of key signaling proteins involved in these processes.
RESULTS: Our results revealed that the combination treatment of B12 and Cispalatin significantly inhibited the proliferation and viability of the PC cell line. Also, clonogenic assay indicated that B12 and Cisplatin combination treatment inhibited the colony formation. In the B12 and cisplatin co-treated groups, our results showed a significant increase in P38 and PARP-1 protein expression compared to the control group. Moreover, B12 combined with cisplatin also downregulated MAPK/ERK1-2 and Bcl-2 protein expression.
DISCUSSION AND CONCLUSION: Our findings suggest that the combination of B12 and Cisplatin enhances the antitumor effects of Cisplatin by promoting apoptosis and modulating key signaling pathways, including P38, PARP-1, and MAPK/ERK1-2. This combination therapy represents a promising approach for improving prostate cancer treatment.