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苯乙基异硫氰酸酯通过产生活性氧和半胱天冬酶来抑制人慢性髓性白血病K562细胞的生长。

Phenethyl isothiocyanate inhibits growth of human chronic myeloid leukemia K562 cells via reactive oxygen species generation and caspases.

作者信息

Wang Yating, Wei Sixi, Wang Jishi, Fang Qin, Chai Qixiang

机构信息

Department of Hematology, First Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.

Department of Pharmacy, First Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550004, P.R. China.

出版信息

Mol Med Rep. 2014 Jul;10(1):543-9. doi: 10.3892/mmr.2014.2167. Epub 2014 Apr 24.

Abstract

Phenethyl isothiocyanate (PEITC), a potential cancer chemopreventive constituent of cruciferous vegetables, including watercress, has been reported to inhibit cancer cell growth by arresting the cell cycle and inducing apoptosis in various human cancer cell models. However, the role of PEITC in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms have yet to be elucidated. In the present study, PEITC was found to induce cell death through the induction of reactive oxygen species (ROS) stress and oxidative damage. Heme oxygenase‑1 (HO‑1), which participates in the development of numerous tumors and the sensitivity of these tumors to chemotherapeutic drugs, plays a protective role by modulating oxidative injury. Therefore, the present study assessed the inhibitory effect of PEITC on K562 cells and whether HO‑1 facilitated cell apoptosis and ROS generation. PEITC was found to suppress cell growth and cause apoptosis by promoting Fas and Fas ligand expression, increasing ROS generation and by the successive release of cytochrome c as well as the activation of caspase‑9 and caspase‑3. PEITC was also combined with the HO‑1 inhibitor zinc protoporphyrin IX and the inducer hemin to assess whether HO‑1 determines cell survival and ROS generation. The results of the present study suggest that PEITC may be a potential anti‑tumor compound for CML therapy, and that HO‑1 has a critical function in PEITC‑induced apoptosis and ROS generation.

摘要

异硫氰酸苯乙酯(PEITC)是十字花科蔬菜(包括西洋菜)中一种潜在的癌症化学预防成分,据报道,在各种人类癌细胞模型中,它可通过阻滞细胞周期和诱导凋亡来抑制癌细胞生长。然而,PEITC在抑制人类慢性髓系白血病(CML)K562细胞生长中的作用及其潜在机制尚未阐明。在本研究中,发现PEITC通过诱导活性氧(ROS)应激和氧化损伤来诱导细胞死亡。血红素加氧酶-1(HO-1)参与多种肿瘤的发生发展以及这些肿瘤对化疗药物的敏感性,通过调节氧化损伤发挥保护作用。因此,本研究评估了PEITC对K562细胞的抑制作用以及HO-1是否促进细胞凋亡和ROS生成。发现PEITC通过促进Fas和Fas配体表达、增加ROS生成以及随后细胞色素c的释放以及caspase-9和caspase-3的激活来抑制细胞生长并导致凋亡。还将PEITC与HO-1抑制剂锌原卟啉IX和诱导剂血红素联合使用,以评估HO-1是否决定细胞存活和ROS生成。本研究结果表明,PEITC可能是一种用于CML治疗的潜在抗肿瘤化合物,并且HO-1在PEITC诱导的凋亡和ROS生成中起关键作用。

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