Das Rakhee, Roy Amit, Dutta Neeta, Majumder Hemanta K
Department of Molecular Parasitology, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
Apoptosis. 2008 Jul;13(7):867-82. doi: 10.1007/s10495-008-0224-7.
Curcumin, a polyphenol compound, has been recognized as a promising anti-cancer drug. The purpose of the present study was to investigate the cytotoxicity of curcumin to Leishmania donovani, the causative agent for visceral leishmaniasis. Flow cytometric analysis revealed that curcumin induced cell cycle arrest at G2/M phase. Incubation of Leishmania promastigotes with curcumin caused exposure of phosphatidylserine to the outer leaflet of plasma membrane. This event is preceded by curcumin-induced formation of reactive oxygen species (ROS) and elevation of cytosolic calcium through the release of calcium ions from intracellular stores as well as by influx of extracellular calcium. Elevation of cytosolic calcium is responsible for depolarization of mitochondrial membrane potential (DeltaPsim), release of Cytochrome c into the cytosol and concomitant nuclear alterations that included deoxynucleotidyltransferase-mediated dUTP end labeling (TUNEL) and DNA fragmentation. Taken together, these data indicate that curcumin has promising antileishmanial activity that is mediated by programmed cell death and, accordingly, merits further investigation as a therapeutic option for the treatment of leishmaniasis.
姜黄素是一种多酚化合物，已被公认为是一种很有前景的抗癌药物。本研究的目的是调查姜黄素对内脏利什曼病病原体杜氏利什曼原虫的细胞毒性。流式细胞术分析显示，姜黄素诱导细胞周期停滞于G2/M期。用姜黄素孵育利什曼原虫前鞭毛体导致磷脂酰丝氨酸暴露于质膜外小叶。这一事件之前会出现姜黄素诱导的活性氧（ROS）形成以及通过从细胞内储存释放钙离子以及细胞外钙内流导致的胞质钙升高。胞质钙升高导致线粒体膜电位（ΔΨm）去极化、细胞色素c释放到胞质溶胶中以及伴随的核改变，包括脱氧核苷酸末端转移酶介导的dUTP缺口末端标记（TUNEL）和DNA片段化。综上所述，这些数据表明姜黄素具有通过程序性细胞死亡介导的有前景的抗利什曼原虫活性，因此，作为治疗利什曼病的一种治疗选择值得进一步研究。
