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

Abstract

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 i n 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. Materials and 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 bl ot 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 o f the PC cell line. Also, clonogenic assay indicated that B12 and Cisplatin combination treatment inhibited the colony formation. Moreover, the combined treatment showed a 2.3-fold increase in P38 and a 1.8-fold increase in PARP-1 protein expression compared to control. In addition, MAPK/ERK1-2 and Bcl-2 protein expression were significantly reduced by approximately 40% and 45% respectively in the combination treatment. 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. These findings, supported by significant reductions in cell viability (up to 50%), suggest a promising role for B12 and Cisplatin combination therapy. Further in vivo and clinical studies are warranted to validate these preliminary in vitro findings. © 2025, Yuzuncu Yil Universitesi Tip Fakultesi. All rights reserved.