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白藜芦醇、二苯甲酰甲烷及其类似物对人肺癌细胞诱导凋亡作用的机制

Mechanisms of apoptotic effects induced by resveratrol, dibenzoylmethane, and their analogues on human lung carcinoma cells.

作者信息

Weng Chia-Jui, Yang Ya-Ting, Ho Chi-Tang, Yen Gow-Chin

机构信息

Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan.

出版信息

J Agric Food Chem. 2009 Jun 24;57(12):5235-43. doi: 10.1021/jf900531m.

DOI:10.1021/jf900531m
PMID:19441815
Abstract

While lung cancer accounts for approximately 20% of cancer diagnoses, it is the leading cause of tumor-related deaths. The apoptotic effects of 3,5,4'-trihydroxystilbene (resveratrol), dibenzoylmethane (DBM), and their analogues on human lung cancer cells are generally unclear. The aims of this study were to evaluate the apoptotic effects and molecular mechanisms of resveratrol, DBM, and their analogues on human lung cancer cells. The results of the MTT and lactate dehydrogenase (LDH) leakage assays indicated that resveratrol, 3,5,4'-trimethoxy-trans-stilbene (MR-3), and 1-(2-hydroxy-5-methylphenyl)-3-phenyl-1,3-propanedione (HMDB) could inhibit cell population growth and induce cell injury in A549 and CH27 cell lines. Resveratrol and HMDB could induce apoptotic cell death in the A549 and CH27 cell lines. Moreover, cellular growth of the A549 and CH27 cell lines might be inhibited by MR-3 through induction of apoptosis and regulation of the cell cycle. The A549 and CH27 cell lines treated with resveratrol, MR-3, and HMDB showed a time-dependent reduction of mitochondrial membrane potential, and the Bax/Bcl-2 ratio increased gradually with a higher concentration of polyphenols. The resveratrol-, MR-3-, and HMDB-induced apoptosis in the A549 and CH27 cell lines were controlled through activation of caspase-9 and caspase-3 and subsequent cleavage of PARP. In conclusion, we have demonstrated that resveratrol, DBM, and their analogues could be effective candidates for chemoprevention of lung cancer and HMDB might have the strongest ability for inducing apoptosis.

摘要

虽然肺癌约占癌症诊断病例的20%,但它是肿瘤相关死亡的主要原因。白藜芦醇(3,5,4'-三羟基茋)、二苯甲酰甲烷(DBM)及其类似物对人肺癌细胞的凋亡作用通常尚不清楚。本研究的目的是评估白藜芦醇、DBM及其类似物对人肺癌细胞的凋亡作用和分子机制。MTT和乳酸脱氢酶(LDH)泄漏试验结果表明,白藜芦醇、3,5,4'-三甲氧基反式茋(MR-3)和1-(2-羟基-5-甲基苯基)-3-苯基-1,3-丙二酮(HMDB)可抑制A549和CH27细胞系的细胞群体生长并诱导细胞损伤。白藜芦醇和HMDB可诱导A549和CH27细胞系发生凋亡性细胞死亡。此外,MR-3可能通过诱导凋亡和调节细胞周期来抑制A549和CH27细胞系的细胞生长。用白藜芦醇、MR-3和HMDB处理的A549和CH27细胞系显示线粒体膜电位呈时间依赖性降低,且随着多酚浓度升高,Bax/Bcl-2比值逐渐增加。白藜芦醇、MR-3和HMDB诱导A549和CH27细胞系凋亡是通过激活caspase-9和caspase-3以及随后切割PARP来控制的。总之,我们已经证明白藜芦醇、DBM及其类似物可能是肺癌化学预防的有效候选物,且HMDB诱导凋亡的能力可能最强。

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