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首页> 外文期刊>Cellular Physiology and Biochemistry >Curcumin blocks Kv11.1 (erg) potassium current and slows proliferation in the infant acute monocytic leukemia cell line THP-1
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Curcumin blocks Kv11.1 (erg) potassium current and slows proliferation in the infant acute monocytic leukemia cell line THP-1

机译：姜黄素阻断Kv11.1（erg）钾电流并减慢婴儿急性单核细胞白血病细胞THP-1的增殖

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摘要

Acute Myeloid Leukemia (AML) accounts for approximately one fifth of all childhood leukemia yet is responsible for a significant proportion of morbidity and mortality in this population. For this reason, research to identify novel targets for the development of effective AML therapeutics has intensified in the recent past. The THP-1 cell line, which was originally established from an infant diagnosed with AML, provides an experimental model for functional, pre-clinical therapeutics and target identification studies of AML. Here we show the expression of the voltage gated potassium channel Kv11.1 in THP-1 cells as opposed to normal hematopoietic stem cells. In addition, curcumin, a natural polyphenol derived from the plant Curcuma longa, effectively blocked Kv11.1 activity and also inhibited the proliferation of these cells. Curcumin was rapidly internalized by THP-1 cells and possibly exerts potential growth inhibitory activity by interacting with intracellular epitopes of the ion channel. Inhibition of ionic currents carried by Kv11.1 resulted in depolarization of cell membrane potential. We propose that the inhibition of Kv11.1 activity by curcumin may lead to interference with leukemic cell physiology and consequently the suppression of survival and proliferation of AML cells.
机译：急性髓细胞性白血病（AML）约占所有儿童白血病的五分之一，但仍占该人群发病率和死亡率的很大比例。由于这个原因，最近为确定有效的AML治疗药物开发的新靶标而进行的研究已经加强。 THP-1细胞系最初是由被诊断患有AML的婴儿建立的，为AML的功能性临床前治疗和靶标鉴定研究提供了实验模型。在这里，我们显示了与正常造血干细胞相对的THP-1细胞中电压门控钾通道Kv11.1的表达。此外，姜黄素是一种源自植物姜黄的天然多酚，可有效阻断Kv11.1活性，并抑制这些细胞的增殖。姜黄素被THP-1细胞迅速内在化，并可能通过与离子通道的细胞内表位相互作用而发挥潜在的生长抑制活性。 Kv11.1携带的离子电流的抑制导致细胞膜电位去极化。我们提出姜黄素抑制Kv11.1活性可能导致干扰白血病细胞生理学，从而抑制AML细胞的存活和增殖。

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