Cholecalciferol Potential in the Treatment of Advanced Cervical Cancer Patients: Evidence for Autophagy and Mitochondrial Mechanisms

Abstract Introduction. Cholecalciferol, also known as vitamin D3, has been investigated in various cancer studies with conflicting results. Cervical cancer, the second most common cancer among women, has a high fatality rate in its advanced stages. Supplementation of cholecalciferol is recommended for cervical cancer patients. There is a significant need to explore potential pathways to understand how cholecalciferol affects cervical cancer, particularly in autophagy mechanisms and mitochondrial function. Methods. An observational study was carried out on 66 patients with advanced-stage cervical cancer at Hasan Sadikin Hospital. These patients received an oral dose of 10,000 IU of cholecalciferol daily during and after radiation therapy. The patients were monitored closely using RECIST criteria. Sixteen patients agreed to have their blood collected to measure cholecalciferol and autophagy biomarkers before and after radiotherapy. The biomarkers targeted for measurement were p62, LC3b1, LC3b2, TOM20, and COX4. Results. All participants exhibited clinical improvement. The average serum cholecalciferol level exceeded 30 ng/ml, indicating that the administered dose was adequate to treat and prevent deficiency. Significant changes were observed in all the studied biomarkers. While p62 and LC3b2 levels increased, LC3b1, TOM20, and COX4 levels decreased significantly. There was no correlation between TOM20 and COX4 levels before radiation; however, a trend towards correlation was noted post-radiation (R=0.488; p=0.055). Conclusion. This study demonstrated that a daily intake of 10,000 IU of cholecalciferol in advanced cervical cancer patients (stages IIB—IVA) undergoing radiotherapy was sufficient to treat and prevent deficiency. The anticipated clinical improvement was achieved. The involvement of autophagy is suggested to play a crucial role in enhancing the effectiveness of radiation treatment.