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白藜芦醇类似物HS-1793可诱导人乳腺癌细胞的细胞周期停滞和凋亡性细胞死亡。

HS-1793, a resveratrol analogue, induces cell cycle arrest and apoptotic cell death in human breast cancer cells.

作者信息

Kim Jin-Ah, Kim Dong Hwan, Hossain Mohammad Akbar, Kim Min Young, Sung Bokyung, Yoon Jeong-Hyun, Suh Hongsuk, Jeong Tae Cheon, Chung Hae Young, Kim Nam Deuk

机构信息

Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.

Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan 609-735, Republic of Korea.

出版信息

Int J Oncol. 2014 Feb;44(2):473-80. doi: 10.3892/ijo.2013.2207. Epub 2013 Dec 5.

Abstract

Resveratrol, a polyphenolic compound, is a naturally occurring phytochemical and is found in a variety of plants, including food such as grapes, berries and peanuts. It has gained much attention for its potential anticancer activity against various types of human cancer. However, the usefulness of resveratrol as a chemotherapeutic agent is limited by its photosensitivity and metabolic instability. In this study the effects of a synthetic analogue of resveratrol, HS-1793, on the proliferation and apoptotic cell death were investigated using MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53) human breast cancer cells. HS-1793 inhibited cell growth and induced apoptotic cell death in a concentration-dependent manner. The induction of apoptosis was determined by morphological changes, cleavage of poly(ADP-ribose) poly-merase, alteration of Bax/Bcl-2 expression ratio and caspase activities. Flow cytometric analysis revealed that HS-1793 induced G2/M arrest in the cell cycle progression in both types of cells. Of note, HS-1793 induced p53/p21WAF1/CIP1-dependent apoptosis in MCF-7 cells, whereas it exhibited p53-independent apoptosis in MDA-MB-231 cells. Furthermore, HS-1793 showed more potent anticancer effects in several aspects compared to resveratrol in MCF-7 and MDA-MB-231 cells. Thus, these findings suggest that HS-1793 has potential as a candidate chemotherapeutic agent against human breast cancer.

摘要

白藜芦醇是一种多酚类化合物,是一种天然存在的植物化学物质,存在于多种植物中,包括葡萄、浆果和花生等食物。它因其对各种人类癌症潜在的抗癌活性而备受关注。然而,白藜芦醇作为一种化疗药物的有效性受到其光敏性和代谢不稳定性的限制。在本研究中,使用MCF-7(野生型p53)和MDA-MB-231(突变型p53)人乳腺癌细胞研究了白藜芦醇的合成类似物HS-1793对细胞增殖和凋亡性细胞死亡的影响。HS-1793以浓度依赖性方式抑制细胞生长并诱导凋亡性细胞死亡。通过形态学变化、聚(ADP-核糖)聚合酶的裂解、Bax/Bcl-2表达比率的改变和半胱天冬酶活性来确定凋亡的诱导。流式细胞术分析显示,HS-1793在两种类型的细胞中均诱导细胞周期进程中的G2/M期阻滞。值得注意的是,HS-1793在MCF-7细胞中诱导p53/p21WAF1/CIP1依赖性凋亡,而在MDA-MB-231细胞中表现出p53非依赖性凋亡。此外,与白藜芦醇相比,HS-1793在MCF-7和MDA-MB-231细胞的几个方面显示出更强的抗癌作用。因此,这些发现表明HS-1793有潜力作为一种抗人类乳腺癌的候选化疗药物。

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