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苯乙烯基吡喃酮衍生物(SPD)在人乳腺癌细胞系MCF-7中以半胱天冬酶-7依赖性方式诱导细胞凋亡。

Styrylpyrone Derivative (SPD) induces apoptosis in a caspase-7-dependent manner in the human breast cancer cell line MCF-7.

作者信息

Lee Alvin Teck Chien, Azimahtol Hawariah Lope Pihie, Tan Ann Na

机构信息

School of Biosciences & Biotechnology, Faculty of Science & Technology, National University of Malaysia, 43600 Bangi, Selangor, MALAYSIA.

出版信息

Cancer Cell Int. 2003 Oct 4;3(1):16. doi: 10.1186/1475-2867-3-16.

Abstract

BACKGROUND

Styrylpyrone derivative (SPD) is a plant-derived pharmacologically active compound extracted from Goniothalamus sp. Previously, we have reported that SPD inhibited the proliferation of MCF-7 human breast cancer cells by inducing apoptotic cell death, while having minimal effects on non-malignant cells. Here, we attempt to further elucidate the mode of action of SPD. RESULTS: We found that the intrinsic apoptotic pathway was invoked, with the accumulation of cytosolic cytochrome c and processing of the initiator caspase-9. Cleaved products of procaspase-8 were not detected. Next, the executioner caspase-7 was cleaved and activated in response to SPD treatment. To confirm that apoptosis was induced following caspase-7 activation, the caspase inhibitor Ac-DEVD-CHO was used. Pre-incubation of cells with this inhibitor reversed apoptosis levels and caspase-7 activity in SPD-treated cells to untreated levels. CONCLUSIONS: Taken together, these results suggest SPD as a potent antiproliferative agent on MCF-7 cells by inducing apoptosis in a caspase-7-dependent manner.

摘要

背景

苯乙烯基吡喃酮衍生物(SPD)是一种从哥纳香属植物中提取的具有药理活性的植物源化合物。此前,我们报道SPD通过诱导凋亡性细胞死亡抑制MCF-7人乳腺癌细胞的增殖,而对非恶性细胞影响极小。在此,我们试图进一步阐明SPD的作用模式。结果:我们发现内在凋亡途径被激活,伴随着胞质细胞色素c的积累和起始半胱天冬酶-9的加工。未检测到procaspase-8的裂解产物。接下来,执行半胱天冬酶-7被裂解并在SPD处理后被激活。为了证实半胱天冬酶-7激活后诱导了凋亡,使用了半胱天冬酶抑制剂Ac-DEVD-CHO。用该抑制剂对细胞进行预孵育可将SPD处理细胞中的凋亡水平和半胱天冬酶-7活性恢复到未处理水平。结论:综上所述,这些结果表明SPD通过以半胱天冬酶-7依赖性方式诱导凋亡,是一种对MCF-7细胞有效的抗增殖剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60af/239923/9beeb35a4d7c/1475-2867-3-16-1.jpg

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