Functional Characterizations of Plant Uracil Phosphoribosyltransferase (UPRT) and Phytaspase for their Potential in Cancer Therapy

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In burgeoning field of cancer research, plant bioactive compounds and plant therapeutic proteins have been found very effective on persisting drug resistant cancer. Although many plant derived compounds are either in market or under clinical trials, there is still need of in-depth analysis on the plant functional proteins. Uracil phosphoribosyltransferase (UPRT) and phytaspase caspase-like protease are two such functional plant proteins, which are reported to have their functional counterparts in bacterial (bUPRT) and mammalian (caspase) system, respectively. In turn, these counterparts have been already very well exploited for their major role in the cancer treatment. Bacterial UPRT, pyrimidine salvage pathway enzyme converts the prodrug 5- FU into toxic metabolite 5-FUMP inside the cancer cells leading to apoptosis. Whereas, caspases are intracellular mammalian cysteine dependent proteases, which are mainly involved in the execution of apoptosis. However, thorough characterization of recombinant AtUPRT and phytaspase, and their potential in complementing their functional counterparts in cancer treatment have been conducted in detail in this current thesis. More specifically, this thesis addresses the raising question of how far these two proteins mimic their counterparts in contributing themselves in the cancer therapy either by gene or by protein therapeutics. In Chapter 1, the emerging importance of cancer gene and protein therapy has been discussed. It also brings the deeper value of preliminarily investigated or yet to be explored plant suicide genes encoding therapeutic protein’s application in cancer therapy into the limelight. More specifically, it deals exclusively with the significance of Arabidopsis thaliana uracil phosphoribosyltransferase (ATUPRT) and Nicotiana tabacum phytaspase. The chapter deciphers the possibilities of utilizing the potential of phytaspase in cancer therapy. The last section of this chapter encompasses on the future significance of devising these recombinant proteins into the mammalian system either exogenously or by expression and finally, through their mode of action sensitizing the cancer cells towards chemotherapeutic drugs. At the end, development of quantum dots embedded polymeric nanocarriers for delivering therapeutic agents have been illustrated.
Supervisor: Siddhartha Sankar Ghosh & Lingaraj Sahoo