PKCI Manipulation by Taxifolin in Human Breast Cancer Management

Abstract

Cancer is considered to be a major public health issue and the second leading cause of deaths worldwide. Breast cancer is the most intermittently occurring type of cancer in women all over the world with an incidence rate that keeps on elevating with age. Mutations in the normal breast cells is a leading cause of breast cancer. An accelerated growth of cells is found in the lobules of the mammary glands. Any abnormality inherited from the mother or father is responsible for causation of 5-10% cancers, 85-90% may be caused due to any genetic aberration or aging process. Over-expression of PKC-iota and impaired Krueppel-like factore-5 drive the process of angiogenesis leading to uncontrolled growth of cells. Up till now many diagnostic techniques have been practiced for breast cancer including MRI, mammography, biopsy, hormonal therapies, computerized tomography etc. but all these approaches have some limitations. Despite of the latest conventional treatments, breast cancer is still irremediable. In the present days, the use of naturally occurring plants flavonoids is the target of attention for the treatment of cancer. This research highlights the role of taxifolin by treating it with breast cancer cell lines namely MDA-MB-231 and MCF-07 for breast cancer management. This study involves the molecular docking of KLF5 and PKC-iota by CB-dock to find out the binding affinities of the proteins and ligand. Both the proteins exhibited encouraging docking scores with taxifolin. For further validation, cell viability assay, migration assay and colony formation assay were performed. The number of viable cells, colony forming and migrating abilities of the cells decreased in a dose-dependent manner whereas at IC50 values of taxifolin viz 180nM and 300nM it reduced to minimum. Apoptosis was induced and the expression of the selective gene was downregulated. Taxifolin performs anti-fungal, anti-bacterial, anti-inflammatory, and anti-cancerous activities and has chemoprotective potential too. Therefore, the study confirms that Taxifolin has multiple properties i.e., antioxidant, anti-tumor, and anti-inflammatory functions in breast cancer treatment and after further verification on humans and animals models it can serve as a potential therapeutic and chemoprotective agent in the management of breast cancer in the years to come.