Procyanidin B2 3,3(″)-di-O-gallate, a biologically active constituent of grape seed extract, induces apoptosis in human prostate cancer cells via targeting NF-κB, Stat3, and AP1 transcription factors.
Procyanidin B2 3,3(″)-di-O-gallate, a biologically active constituent of grape seed extract, induces apoptosis in human prostate cancer cells via targeting NF-κB, Stat3, and AP1 transcription factors.
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DOI：
10.1080/01635581.2013.783602
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Agarwal C
中科院分区：
文献类型：
--
作者：
Tyagi A;Raina K;Shrestha SP;Miller B;Thompson JA;Wempe MF;Agarwal R;Agarwal C
最近，我们发现原花青素B2 3，3“-二氧没食子酸酯(B2G2)是葡萄籽提取物(GSE)中最有效的抗前列腺癌(Pca)活性成分。从总的GSE中分离大量的B2G2是劳动密集型和昂贵的，因此限制了这种新型抗癌剂的疗效和机制研究。因此，在这里，我们合成了克量级的B2G2，将其与从GSE中分离的B2G2进行了可能的相同生物活性的比较，并进行了机理研究。这两种B2G2制剂都抑制了不同的人前列腺癌细胞系的细胞生长，降低了克隆形成能力，并诱导了细胞周期停滞和细胞凋亡性死亡。对参与细胞凋亡和存活途径的转录因子的机制研究表明，B2G2显著抑制PCa细胞系中κB和AP1的转录活性和STAT3的核转位，而与其雄激素受体功能状态无关。B2G2还降低了受NF-κB、AP1和STAT3调控的Survivin的表达，增加了裂解的PARP水平。综上所述，我们报道了克量的B2G2化学合成，对人前列腺癌细胞株具有同等的生物学效力，并在关键转录因子水平上进行了相同的分子靶向研究。合成的B2G2将在临床前模型和临床翻译中刺激更多关于前列腺癌和可能的其他恶性肿瘤的研究。
Recently, we identified procyanidin B2 3,3″-di-O-gallate (B2G2) as most active constituent of grape seed extract (GSE) for efficacy against prostate cancer (PCa). Isolating large quantities of B2G2 from total GSE is labor intensive and expensive, thereby limiting both efficacy and mechanistic studies with this novel anti-cancer agent. Accordingly, here we synthesized gram-scale quantities of B2G2, compared it with B2G2 isolated from GSE for possible equivalent biological activity, and conducted mechanistic studies. Both B2G2 preparations inhibited cell growth, decreased clonogenicity, and induced cell cycle arrest and apoptotic death, comparable to each other, in various human PCa cell lines. Mechanistic studies focusing on transcription factors involved in apoptotic and survival pathways revealed that B2G2 significantly inhibits NF-κB and AP1 transcriptional activity and nuclear translocation of Stat3 in PCa cell lines, irrespective of their functional androgen receptor status. B2G2 also decreased survivin expression which is regulated by NF-κB, AP1 and Stat3, and increased cleaved PARP level. In summary, we report B2G2 chemical synthesis at gram-quantity with equivalent biological efficacy against human PCa cell lines and same molecular targeting profiles at key transcription factors level. The synthetic B2G2 will stimulate more research on prostate and possibly other malignancies in preclinical models and clinical translation.
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影响因子：
4.2
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