Apigenin-Melatonin: a novel prostate cancer Radiation Sensitizer

Abstract Background: Radiotherapy is a common modality in prostate cancer (PrCa), with a dose of 80Gy. A higher dose of ionizing radiation is often needed to achieve an appropriate response; however, clinical evidence indicates that increasing the dose may lead to side effects. Therefore, finding a substance that sensitizes PrCa to ionizing radiation improves radiotherapy’s therapeutic efficacy. Thus, we aimed to assess the radiosensitization effect of Apigenin-Melatonin on Lymph Node Carcinoma of the Prostate (LNCaP). Method: The effect of Apigenin, Melatonin, and ionizing radiation, alone and together, on the cells' viability plus the apoptosis induction, were tested by MTT assay, Annexin V, and PI. In addition, Bax and Bcl-2 genes expression was assessed by real-time PCR. Results: LNCaP co-treatment by Apigenin and Melatonin inhibited PrCa cells' viability synergically. Also, LNCaP co-treatment with Apigenin and Melatonin, 2h before radiotherapy, significantly reduced the LNCaP cells' viability compared to the cells co-treated by Apigenin and Melatonin. Also, LNCaP co-treatment with Apigenin, Melatonin, and ionizing radiation significantly increased early apoptosis by decreasing Bcl-2 gene expression and increasing Bax gene expression. Discussion: Our results revealed that Apigenin-Melatonin reduces LNCaP cells' viability. Plus, Apigenin-Melatonin could overcome the radioresistance of the LNCaP cells, enhancing radiation-induced apoptosis.