STUDY OF MANGIFERIN ISOLATED FROM LEAVES OF MANGIFERA INDICA ON MYELOID LEUKEMIA ALONG WITH DIFFERENT HUMAN CANCER CELL LINESAbstract
In different myeloid leukemia cases resistance to diverse treatment regimen owes to multiple molecular mechanisms of cellular network. Epigenetic dysregulation, gene mutations, overexpression of multidrug resistance genes, abnormal immune function, the presence of chemotherapy-resistant leukemia-initiating cells, and aberrant signaling pathways could be the lead cause of this kind of aberration. Some marketed drug is considered as a first-generation drug that can inhibit the enzymatic action by inhibiting the ATP binding with different key pathway regulator protein. Later on, insensitivity of myeloid leukemia cells towards these drugs has been observed may be due to mutation in tyrosine kinase domain of the kinase receptor. By enchanting into account of bioavailability and resistance developed, there is an extreme need to find some natural and nature-derived inhibitors for the kinase proteins of different key metabolic pathways. For computational screening and in-vitro studies against cancer cell lines and marker proteins, Mangiferin and Euxanthic acid isolated from leaves of Mangifera indiaca had been used as mentioned in Ayurveda / Indian Traditional Medicine (ITM). Docking analysis was also carried out on the active site of different tyrosine kinase receptors with reported reference inhibitors. A series of in-vitro tests were done to validate the stability of the system. The anti-proliferative effect of Mangiferin as tested and was found to inducing cell death with IC50 values 149 µg/ml in K-562 and 297 µg/ml in Jurkat cells respectively. Considering the above-said parameters proposed Mangiferin molecule is concluded as potential lead for drug designing pipeline against myeloid leukemia.
H. K. Manikyam
Faculty of Science, Department of Chemistry, North East Frontier Technical University, Aalo, Arunachal Pradesh, India.
22 August 2019
16 November 2019
26 November 2019
01 December 2019