Novel Colchicine Analogues Target Mitochondrial PT Pores Using Free Tubulins and Induce ...

In this study, the effects of two newly synthesized of colchicine derivatives were investigated on cell viability of cancerous and normal lymphocytes. The viability test was carried out by MTT assay. Apoptosis vs. necrosis was measured by double staining with annexin V/PI, and caspase-3 as the ultimate mediator of apoptotic measured through the colorimetric assay. Parameters of mitochondrial damage (ROS formation, MMP decline, mitochondrial swelling, and cytochrome c release following treatment by colchicine derivatives. By focusing on mitochondrial parameters, we showed that following treatment by two newly synthetized colchicine derivatives, apoptosis are triggered in cancerous B-lymphocytes. We demonstrated these compounds could activate apoptosis in cancerous lymphocytes by augmentation of reactive oxygen species (ROS), a decline in mitochondrial membrane potential (MMP), mitochondrial swelling, release of cytochrome c and also caspase-3 activation. Considering the obtained evidences, these inhibitorscould be the new therapeutic strategies in ALL treatment.
Source: Iranian Journal of Pharmaceutical Research - Category: Drugs & Pharmacology Source Type: research