Versatility of berberine as an effective immunomodulator and chemo sensitizer against p53 mutant cell

Abstract

Cancer is the leading cause of death among individuals due to its poor prognosis. Various therapeutics treatments are available in form radiation therapy, chemotherapy, or immunotherapy but major point of concern is the treatment of cancer resistant cell lines. Homozygous loss of the p53 gene is virtually present in every type of cancer. Mutation in DNA binding domain of p53 leads to formation of mutant forms having altered amino acid sequence which lacks DNA binding activity. Berberine is chemo-sensitizing isoquinoline quaternary alkaloid molecule obtained from Berberis vulgaris. Berberine has the capability to suppress the growth of broad range of tumors. It exhibits pharmacological, biochemical and anticancer properties which can potentiate the activities of the existing therapeutics available in a way that it can re-sensitize the cancer resistant clones. Berberine has an immanent potential to bind with DNA and can communicate with several cellular targets, further it also shows hormetic effect which refers to biphasic dose response curve in order to determine dose dependent stimulatory and inhibitory effect. Mode of action involved is yet not well understood but mechanistic pathway involved are autophagy, up-regulation of tumor-suppressor gene (p53) and epigenetic alterations in the viral DNA. In this review, versatility of berberine can be utilized ideally or in combination with chemotherapeutics drugs to potentiate chemo sensitization of the resistant cancer cell line. Further, cancer cell specific receptor targeting can also be employed in combination with berberine for therapeutic treatment of metastasizing cancer cells.