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石蒜甾醇-3-醇对人白血病 HL-60 细胞和人乳腺癌 MCF-7 细胞的促凋亡和抗增殖作用。

Apoptotic and antiproliferative effects of Stigmast-5-en-3-ol from Dendronephthya gigantea on human leukemia HL-60 and human breast cancer MCF-7 cells.

机构信息

Department of Marine Life Science, Jeju National University, Jeju 63243, Republic of Korea.

Choung Ryong Fisheries Co. Ltd., 7825, Iljudong-ro, Namwon-eup, Seogwipo-si, Jeju-do, Republic of Korea.

出版信息

Toxicol In Vitro. 2018 Oct;52:297-305. doi: 10.1016/j.tiv.2018.07.007. Epub 2018 Jul 19.

Abstract

The genus Dendronephthya encompasses marine soft corals that produce a wide spectrum of biofunctional terpenoids. Anticancer properties of these metabolites are widely exploited as potential chemotherapeutic agents. The present study reports the purification and isolation of a potential antiproliferative constituent, stigmast-5-en-3-ol from the 70% ethanol extract of the soft coral Dendronephthya gigantea. Among several other 3β-hydroxy-Δ5-steroidal congeners, stigmast-5-en-3-ol indicated prominent antiproliferative effects on HL-60 (leukemia) and MCF-7 (breast cancer) cell lines with IC values of 37.82 and 45.17 μg/ml respectively. Stigmast-5-en-3-ol increased apoptotic body formation, accumulation of sub G1 apoptotic cells, and DNA damage in HL-60 and MCF-7 cells. It increased the expression of Bax, caspases, and PARP cleavage while decreasing Bcl-xL levels in both cancer cell lines indicating that the effects are arbitrated via the mitochondria-mediated apoptotic pathway. Steroidal derivatives were identified by GC MS/MS and the identity of stigmast-5-en-3-ol was confirmed by NMR spectra. The present study suggests that stigmast-5-en-3-ol could be a promising candidate for anticancer drug research.

摘要

该属的软珊瑚生产各种生物功能萜烯。这些代谢物的抗癌特性被广泛用作潜在的化疗药物。本研究报告了从软珊瑚 Dendronephthya gigantea 的 70%乙醇提取物中纯化和分离潜在的抗增殖成分麦角甾-5-烯-3-醇。在其他几种 3β-羟基-Δ5-甾体同系物中,麦角甾-5-烯-3-醇对 HL-60(白血病)和 MCF-7(乳腺癌)细胞系表现出明显的抗增殖作用,IC 值分别为 37.82 和 45.17μg/ml。麦角甾-5-烯-3-醇增加了 HL-60 和 MCF-7 细胞中凋亡小体的形成、亚 G1 凋亡细胞的积累和 DNA 损伤。它增加了 Bax、caspases 和 PARP 切割的表达,同时降低了两种癌细胞系中 Bcl-xL 的水平,表明这些作用是通过线粒体介导的凋亡途径介导的。甾类衍生物通过 GC-MS/MS 鉴定,麦角甾-5-烯-3-醇的鉴定通过 NMR 谱证实。本研究表明,麦角甾-5-烯-3-醇可能是抗癌药物研究的有前途的候选物。

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