Inhibition of mutant P53 tumour cells by medicinal plants
Posted: 4 May 2016 | | No comments yet
The aetiology of tumours is attributed to changes in many internal (molecular) factors, most of which include mutations in several regulatory mechanisms and the loss of cell differentiation. Human isoforms of the p53 protein play a key role in maintaining genetic stability, functioning as active tumour suppressors. However, a mutation of the p53 gene leads to the production of mutant p53 protein, which contributes to the progression of malignancy. A large amount of work has been undertaken to understand the complex role of mutant p53 in malignancies, yet fairly little has been achieved using synthetic formulations to counter tumour metastasis. This article aims at reviewing the current advances in p53 research, as well as discussing the possibilities of inhibiting the expression and activity of mutant p53 genes in human malignancies through the use of medicinal plants.
Introduction Cancer, the uncontrolled proliferation of cells, arises due to mutations in either the DNA repair mechanisms, tumour suppressor genes or selected oncogenes1 . It results in the production of a massive amount of undifferentiated cells which form unwanted protuberances known as malignant tumours. Tumours that grow and develop in specific tissues are referred to as benign, while those that grow, develop and spread to other tissues (a condition referred to as metastasis) are described as malignant tumours. Only these malignant tumours (with a few exceptions) cause cancers2 with cancers sometimes therefore being called malignancies.
Tumour suppression gene products are produced by cells to monitor the efficiency of the cell cycle by populating specific phases in the process of both DNA and cell replications1. The p53 gene is one of the most intensively studied tumour suppressor genes. Initially, when p53 proteins were first discovered, they were understood to be tumour-promoting proteins. A greater understanding of p53 protein was achieved during a study of the human papilloma virus (HPV) in 19801. It was shown that this virus possesses specific proteins, called tumour antigens, which bind wild type-p53 proteins. The main effect of this binding is that, firstly, the protein loses its function1 and, secondly, it becomes an oncoprotein that promotes tumour formation and metastasis3…