Forskolin Attenuates Doxorubicin-induced Accumulation of Asymmetric Dimethylarginine and s-Adenosylhomocysteine via Methyltransferase Activity in Leukemic Monocytes

Publication date: Available online 23 February 2018 Source:Leukemia Research Reports Author(s): Sandhiya Ramachandran, Swetha Loganathan, Vinnie Cheeran, Soniya Charles, Ganesh Munuswamy-Ramanujan, Mohankumar Ramasamy, Vijay Raj, Kanchana Mala Doxorubicin (DOX) is an antitumor drug, associated with cardiomyopathy. Strategies to address DOX-cardiomyopathy are scarce. Here, we identify the effect of forskolin (FSK) on DOX-induced-asymmetric-dimethylarginine (ADMA) accumulation in monocytoid cells. DOX-challenge led to i) augmented cytotoxicity, reactive-oxygen-species (ROS) production and methyltransferase-enzyme-activity identified as ADMA and s-adenosylhomocysteine (SAH) accumulation (SAH-A). However, except cytotoxicity, other DOX effects were decreased by metformin and FSK. FSK, did not alter the DOX-induced cytotoxic effect, but, decreased SAH-A by >50% and a combination of three drugs restored physiological methyltransferase-enzyme-activity. Together, protective effect of FSK against DOX-induced SAH-A is associated with mitigated methyltransferase-activity, a one-of-a-kind report. Graphical abstract
Source: Leukemia Research Reports - Category: Hematology Source Type: research