Life Sciences & Biotechnology
Title : | Enterocins and enterocin-derived peptides as anticancer agents |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Sukhraj Kaur, Guru Nanak Dev University, Punjab |
Timeline Start Year : | 2022 |
Timeline End Year : | 2025 |
Contact info : | drsukhrajkaur@gmail.com |
Equipments : | HPLC column and gaurd column |
Details
Executive Summary : | Cancer is the second leading cause of deaths worldwide that accounted for an estimated 9.6 million deaths in 2018. Despite several therapeutic strategies available, treatment of cancer remains a formidable task. Chemotherapeutic drugs employed for the treatment of cancer mostly have non-specific cytotoxicity towards normal cells. Secondly, dormant cancer stem cells owing to slow rate of growth respond poorly to therapeutic agents that mostly target proliferating cells. Moreover, in due course of treatment, cancer cells are known to develop resistance to the chemotherapeutic drugs.Therefore, there is an urgent need to develop novel and safe anticancer agents that have higher degree of selectivity for cancer cells. Cationic antimicrobial peptides (CAPs) secreted from wide variety of organisms as part of their innate immune defence have demonstrated exciting potential as a new class of anticancer agents. Being cationic in nature, CAPs are known to specifically permeabilise the negatively charged cell membrane of cancer cells due to net negative charge and abundance of microvilli on cancer cells as compared to normal cells. Once inside the cytoplasm, CAPs may damage mitochondrial membrane resulting in the release of several apoptosis-inducing proteins. Moreover, dormant cancer stem cells with a chemoresistant phenotype are predicted to be sensitive to CAPs that kill by direct membrane lysis and does not depend on proliferative status of cells. Although the anticancer activities of CAPs of mammal, and insects is well known, their heterologus expression is quite challenging as compared to bacteria. Bacterial CAPs are known as bacteriocins.The bacteriocins of lactic acid bacteria (LAB) have GRAS (generally regarded as safe) status and their anticancer activities are not much reported. Thus, this project aims to purify and characterise anticancer enterocin from the LAB strain Enterococcus faecium L12b and E20c that were isolated earlier from the microflora of healthy women in the laboratory of PI. Further, the anticancer activities of the purified enterocins will be tested against human cancer cell lines and dormant cancer cells in vitro. In order to increase the production of enterocins in culture supernatant, the genes of any one of the most promising enterocin will be cloned. Furthermore, the sequence knowledge of the purified anticancer proteins will be utilised to rationally design the truncated 15-25 amino acid long synthetic peptides. The anticancer properties, toxicities and cell membrane penetration of synthetic peptides will also be tested, in vitro. |
Total Budget (INR): | 29,85,400 |
Organizations involved