阿霉素、DNA扭转与染色质动力学
Doxorubicin, DNA torsion, and chromatin dynamics.
作者信息
Yang Fan, Teves Sheila S, Kemp Christopher J, Henikoff Steven
机构信息
Basic Science Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
出版信息
Biochim Biophys Acta. 2014 Jan;1845(1):84-9. doi: 10.1016/j.bbcan.2013.12.002. Epub 2013 Dec 19.
Abstract
Doxorubicin is one of the most important anti-cancer chemotherapeutic drugs, being widely used for the treatment of solid tumors and acute leukemias. The action of doxorubicin and other anthracycline drugs has been intensively investigated during the last several decades, but the mechanisms that have been proposed for cell killing remain disparate and controversial. In this review, we examine the proposed models for doxorubicin action from the perspective of the chromatin landscape, which is altered in many types of cancer due to recurrent mutations in chromatin modifiers. We highlight recent evidence for effects of anthracyclines on DNA torsion and chromatin dynamics that may underlie basic mechanisms of doxorubicin-mediated cell death and suggest new therapeutic strategies for cancer treatment.
摘要
阿霉素是最重要的抗癌化疗药物之一，广泛用于实体瘤和急性白血病的治疗。在过去几十年中，人们对阿霉素和其他蒽环类药物的作用进行了深入研究，但提出的细胞杀伤机制仍然各不相同且存在争议。在本综述中，我们从染色质景观的角度审视了阿霉素作用的提出模型，由于染色质修饰剂的反复突变，在许多类型的癌症中染色质景观都发生了改变。我们强调了蒽环类药物对DNA扭转和染色质动力学影响的最新证据，这些可能是阿霉素介导的细胞死亡基本机制的基础，并提出了癌症治疗的新策略。
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