Abstract
Background: P53 was identified as the first tumor suppressor gene actively involved in numerous cellular mechanisms such as initiating DNA repair mechanisms, apoptosis, and cell cycle arrest. More than 50% of all human cancers have a mutated nonfunctional p53 expression. Breast cancer (BC) is one of the leading causes of mortality in females and mutated p53 is documented to be the causative agent in only 20% of them. However, a mutation in p53 in BC results in a more aggressive form of cancer which is more resistant to conventional therapies. Recently multiple clinical trials suggested that the combined use of melatonin and vitamin D3 can slow down the growth of breast cancer cells. The genetic and molecular mechanisms through which these compounds initiate the cancerous cells to apoptosis or cell cycle arrest is still not fully understood. This study aims to investigate the effect of melatonin, vitamin D3, and their combined treatment on the gene expression of P53 in MCF-7 breast cancer cell line. Methods: The optimum treatment dose for melatonin and vitamin D3 were found by MTT and LDH assay. MCF-7 breast cancer cell line were treated with this optimum concentration, and studied the gene expression of p53 by RTPCR and concomitant protein expression by western blots analysisResults: This study indicated that 5nM melatonin, 0.5nM vitamin D3, and their combined treatment inhibited the proliferation of MCF-7 breast cancer cells and caused apoptosis by upregulating the p53 gene expression (2-fold) and significant increase (p<0.001) in p53 protein expression. Conclusion: Treatments with melatonin and vitamin D3 were found to have anti-cancerous effect and could potentially prove to be the ideal natural adjuvant therapy for the treatment of breast cancer.
The antitumor activities of curcumin and of its isoxazole analogue are not affected by multiple gene expression changes in an MDR model of the MCF-7 breast cancer cell line: Analysis of the possible molecular basis
