>
Fa   |   Ar   |   En
   Novel Colchicine Analogues Target Mitochondrial PT Pores Using Free Tubulins and Induce ROS-Mediated Apoptosis in Cancerous Lymphocytes  
   
نویسنده aghvami marjan ,eshghi peyman ,zarei mohammad hadi ,arefi hadi ,sattari fatemeh ,zarghi afshin ,pourahmad jalal
منبع iranian journal of pharmaceutical research - 2018 - دوره : 17 - شماره : 4 - صفحه:1476 -1487
چکیده    B-acute lymphoblastic leukemia (b-all) is the frequent pediatric malignity. chemotherapy is the most practical approaches to deal with such malignancies. microtubule-targeted agentsare one of the most strategic drugs which formerly used in chemotherapy. although colchicine binding anti-tubulin agents exhibited promising effects in clinical trials, their exact mechanism of action is not fully understood. 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 (mitochondrial membrane potential) 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 synthesized colchicine derivatives, apoptosisis triggered in cancerous b-lymphocytes. we demonstrated these compounds could activate apoptosis in cancerous lymphocytes by augmentation of reactive oxygen species (ros), adecline in mitochondrial membrane potential (mmp), mitochondrial swelling, release of cytochrome c, and also caspase-3 activation. considering the obtained evidence, these inhibitors could be the new therapeutic strategies in all treatment.
کلیدواژه B-acute lymphoblastic leukemia; Microtubules inhibitors; Mitochondria; VDAC; Caspase cascade; Apoptosis.
آدرس shahid beheshti university of medical sciences, school of pharmacy, Iran, shahid beheshti university of medical sciences, pediatric congenital hematologic disorders research center, Iran, shahid beheshti university of medical sciences, school of pharmacy, Iran, shahid beheshti university of medical sciences, school of pharmacy, Iran, shahid beheshti university of medical sciences, pediatric congenital hematologic disorders research center, Iran, shahid beheshti university of medical sciences, school of pharmacy, Iran, shahid beheshti university of medical sciences, school of pharmacy, Iran
پست الکترونیکی zarghi@sbmu.ac.ir; j.pourahmadjaktaji@utoronto.ca
 
     
   
Authors
  
 
 

Copyright 2023
Islamic World Science Citation Center
All Rights Reserved