Molecular mechanism of anticancer activity of phycocyanin in triple negative breast cancer cells

Abstract

Triple negative breast cancers represent an important clinical challenge as these cancers do not respond to conventional endocrine therapies or other available targeted agents. Phycocyanin PC a natural water soluble and non toxic molecule is shown to have potent anti cancer property In this study we determined the efficacy of PC as an anti-neoplastic agent in vitro on a series of breast cancer cell lines We studied effects of PC in inducing DNA damage and apoptosis through western blot and qPCR Also, antimetastatic and anti angiogenic properties were studied by classic wound healing and vasculogenic mimicry assays We found that triple negative MDA MB 231 cells were most sensitive to PC as compared to other cells They also showed decreased cell proliferation and reduced colony formation ability upon treatment with PC. Profile of Cell cycle analysis showed that PC caused G1 arrest which could be attributed to decreased mRNA levels of Cyclin E and CDK2 and increased p21 levels. Mechanistic studies revealed that PC induced apoptosis as evident by increase in percentage of annexin positive cells increase in H2AX levels and by changing the Bcl2 Bax ratio followed by release of cytochrome C and increased Caspase 9 levels MDA MB 231 cells treated with PC resulted in decreased cell migration and increased cell adhesive property and also showed anti angiogenic effects We also observed that PC suppressed cyclooxygenase 2 expression and prostaglandin E2 production All these biological effects of phycocyanin on MDA MB 231 cells could be attributed to decreased MAPK signaling pathway We also observed that PC is non toxic to non-malignant cells platelets and RBCs Taken together, these findings demonstrate for the first time, that PC may be a promising anti neoplastic agent for treatment of triple negative breast cancers newline