Validating the use of p53-cannabidiol co-treatment as endogenous biomarker for treatment of cervical cancer
Abstract
Cervical cancer remains the most diagnosed gynaecological malignancy in women worldwide. The lack of resources and high HIV/AIDS incidences occurring in Sub-Saharan Africa are assumed to be some of the contributing factors to the annual increase in the mortality of cervical malignancies. Loss of p53 function seem to be the common characteristic in the cervical cells of many patients with cervical cancer. During cervical tumorigenesis, the p53 tumour suppressor gene becomes degraded by the activity of HPV 16 and 18, thus, allowing the uncontrolled cell division. Despite the p53 restoration and expression in cervical cancer, the p53 gene therapy is resisted due to nonspecific nature of the drugs to the cancer cells. The existing therapy is known to affect normal cells in patients suffering from cervical cancer leading to the developments of phenotypic side effects in patients. As a result, the implementation of natural compounds in the treatment of cancer seem to provide an attractive field that would result in a reliable therapeutic agent against many cancers. In the current study, p53 targeted therapy was used in combination with cannabidiol compound for treatment of metastatic cervical cancer. In the study, the aim was to inhibit growth of cervical cancer with minimal toxicity to humans and this was achieved by conducting the MTT assay, real-time PCR, caspase 3/7 assay, DNA fragmentation and morphology analysis through fluorescence microscopy. The results have shown that the cannabidiol compound inhibited the ME-180 cells in a concentration-dependent manner with an IC50 of 3μg/ml. The cotreatment of p53-cannabidiol seemed to induce the over-expression of p53 in the ME-180 cells which further facilitated the cell cycle arrest as was confirmed by the knockdown of CDK2. The results from caspase 3/7 assay and DNA fragmentation implicated that the p53-cotreatmet has not only arrested cell cycle but also stimulated the apoptotic cell death in the cells. The apoptotic cell death induced by the p53cannabidiol cotreatment was confirmed through analysis of the cell morphology which implied to be that of apoptosis as cell shrinkage and other apoptotic properties were observed. Overall, the p53-cannabidiol compound is the recommended therapeutic tool with potency to treat human cervical cancer.