Towards establishment of a plant-based model to assess the novel anti-cancerous lead molecule(s): An in silico, in vivo and in vitro assessment of some potential anti-cancerous drugs on Lathyrus sativus L

Abstract

The drug development process is one of the important aspects of medical biology. The classical lead identification strategy in the way of drug development based on animal cell is time-consuming, expensive and involving ethical issues. The following study aims to develop a novel plant-based screening of drugs. Study shows the efficacy of certain anti-cancerous drugs (Pemetrexed, 5-Fluorouracil, Methotrexate, Topotecan and Etoposide) on a plant-based (Lathyrus sativus L.) system. Two important characteristics of cancer cells were observed in the colchicine-treated polyploid cell and the callus, where the chromosome numbers were unusual and the division of cells were uncontrolled respectively. With increasing concentration, the drugs significantly reduced the mitotic index, ploidy level and callus growth. Increasing Pemetrexed concentration decreased the plant DHFR activity. A decrease in total RNA content was observed in 5-FU and Methotrexate with increasing concentrations of the drugs. Etoposide and Topotecan inhibited plant topoisomerase II and topoisomerase I activities, which was justified through plasmid nicking and comet assay, respectively. Molecular and biochemical study revealed similar results to the animal system. The in silico study had been done, and the structural similarity of drug binding domains of L. sativus and human beings had also been established. The binding site of the selected drugs to the domains of plant target proteins was also determined. Experimental results are significant in terms of the efficacy of known anti-cancerous drugs on the plant-based system. The proposed assay system is a cost-effective, convenient and less time-consuming process for primary screening of anti-cancerous lead molecules.

Keywords: Alkylating drug; Callus growth; Grass pea; Mitotic index; Polyploidy cell.