Executive Summary : | Cellular redox homeostasis through autophagy-NRF2 colossal nexus has been under investigation for its potential to deliver key a target for anticancer therapeutics. The ever-increasing cancer incidences along with adverse therapeutic outcomes associated with chemotherapy, radiotherapy, and drug resistance have promoted the use of natural products as non-toxic, cost-effective, and target-specific anticancer agents in the recent years. Among the natural products, the marine-derived anticancer compounds represent a diverse class of highly potent anticancer agents targeting the cancer associated pathways. However, the isolation, productive yield and detailed mechanism of action is under investigated. Hence, the proposal aims to isolate and characterize the natural compound ulvan from green seaweed i.e., Ulva compressa of Chilika lagoon. The conformational characterization of ulvan will be done via chromatographic techniques (Gel filtration Chromatography, Ion-exchange Chromatography, HPLC), ATR-FTIR and mass spectroscopic analysis followed by a mechanistic investigation by in vitro reconstitution models for analyzing their antioxidant properties. Further, the autophagy inducing potential of the isolates will be checked in the oral cancer (Cal33 and FaDu) cell lines. A mechanistic investigation on the autophagic degradation of NRF2 will be investigated in the presence and absence of autophagy inhibitors and the redox state of the cell will be evaluated via evaluating the antioxidant enzymes. Further, the impact of autophagic degradation of NRF2 on apoptosis will be evaluated in addition to the evaluation of autophagic and pyroptotic cell death in apoptosis resistance cells. |