福斯高林可减轻阿霉素诱导的白血病单核细胞中不对称二甲基精氨酸的积累及S-腺苷同型半胱氨酸甲基转移酶活性。

Forskolin attenuates doxorubicin-induced accumulation of asymmetric dimethylarginine and s-adenosylhomocysteine methyltransferase activity in leukemic monocytes.

作者信息

Ramachandran Sandhiya, Loganathan Swetha, Cheeran Vinnie, Charles Soniya, Munuswamy-Ramanujan Ganesh, Ramasamy Mohankumar, Raj Vijay, Mala Kanchana

机构信息

Department of Biotechnology, School of Bioengineering, SRM University, Kattankulathur 603203, India.

Interdisciplinary Institute of Indian System of Medicine, SRM University, Kattankulathur 603203, India.

出版信息

Leuk Res Rep. 2018 Feb 23;9:28-35. doi: 10.1016/j.lrr.2018.02.001. eCollection 2018.

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.

阿霉素（DOX）是一种抗肿瘤药物，与心肌病有关。解决阿霉素诱导的心肌病的策略很少。在这里，我们确定了福斯高林（FSK）对阿霉素诱导的单核细胞样细胞中不对称二甲基精氨酸（ADMA）积累的影响。阿霉素刺激导致：i）细胞毒性增强、活性氧（ROS）产生增加以及被鉴定为ADMA和S-腺苷同型半胱氨酸（SAH）积累（SAH-A）的甲基转移酶活性增强。然而，除细胞毒性外，二甲双胍和FSK可降低阿霉素的其他作用。FSK并未改变阿霉素诱导的细胞毒性作用，但使SAH-A降低了50%以上，三种药物联合使用可恢复生理甲基转移酶活性。总之，FSK对阿霉素诱导的SAH-A的保护作用与甲基转移酶活性降低有关，这是一份独一无二的报告。