2012年，美国将会有差不多12000人死于头颈部癌(head and neck cancer)，而在全世界，人数将会超过50万。
2012年1月19日在线发表在Carcinogenesis期刊上的一项研究表明在细胞系和模式小鼠中，葡萄籽抽提物(grape seed extract, GSE)杀死头颈部鳞状细胞癌细胞，但同时不伤害健康细胞。
美国科罗拉多大学癌症中心研究员Rajesh Agarwal博士，也是史卡格斯制药科学学院(Skaggs School of Pharmaceutical Sciences)的教授，他说，“它产生极其大的影响”。
Agarwal说，它大部分上依赖于健康细胞等待伤害结束的能力。
Agarwal说，“癌细胞是迅速生长的细胞。不仅如此，它们必然是迅速生长的。当它们不能生长的条件存在时，它们就死亡。”
葡萄籽抽提物产生这些不适合癌细胞生长的条件。特别地，这篇论文表明葡萄籽抽提物(通过增加的活性氧)对癌细胞的DNA造成伤害，同时也阻止允许DNA修复的途径(就像观察到的DNA修复分子Brca1、Rad51和DNA修复焦点的水平下降)。
Agarwal说，“但是我们完全没有观察到(葡萄籽抽提物)对小鼠本身有任何毒性。”
在模式小鼠中，葡萄籽抽提物再次只杀死癌细胞，而不杀死健康细胞。
Agarwal说，“我认为最重要的一点就是癌细胞拥有大量有缺陷的途径，如果人们靶向这些途径，它们就变得非常脆弱。但同样的情况不适合于健康细胞。”
Agarwal实验室希望葡萄籽抽提物进入临床试验，潜在性地作为头颈部鳞状细胞癌在首次治疗失败后的二线治疗。(生物谷：towersimper编译)
doi:10.1093/carcin/bgs019
PMC:
PMID:
Generation of reactive oxygen species by grape seed extract causes irreparable DNA damage leading to G2/M arrest and apoptosis selectively in head and neck squamous cell carcinoma cells
Sangeeta Shrotriya, Gagan Deep, Mallikarjuna Gu, Manjinder Kaur, Anil K. Jain, Swetha Inturi, Rajesh Agarwal and Chapla Agarwal
Head and neck squamous cell carcinoma (HNSCC) accounts for 6% of all malignancies in United States, and unfortunately, the recurrence of secondary primary tumors and resistance against conventional treatments decrease the overall 5-year survival rate in HNSCC patients. Thus, additional approaches are needed to control HNSCC. Here, for the first time, employing human HNSCC Detroit 562 and FaDu cells as well as normal human epidermal keratinocytes (NHEK), we investigate grape seed extract (GSE) efficacy and associated-mechanism in both cell culture and nude mice xenografts. GSE selectively inhibited the growth, and caused cell cycle arrest and apoptotic death in both Detroit 562 and FaDu cells by activating DNA damage check-point cascade including ATM/ATR-Chk1/2-Cdc25C as well as caspases 8, 9 and 3. Consistent with these results, GSE treatment resulted in a strong DNA damage, and a decrease in the levels of DNA repair molecules Brca1 and Rad51 and DNA repair foci. GSE-caused accumulation of intra-cellular reactive oxygen species (ROS) was identified as a major mechanism of its effect for growth inhibition, DNA damage and apoptosis, which was remarkably reversed by antioxidant N-acetylcysteine. GSE feeding to nude mice decreased Detroit 562 and FaDu xenograft tumor growth by 67% and 65% (p<0.001), respectively. In IHC analysis, xenografts from GSE-fed groups showed decreased proliferation but increased DNA damage and apoptosis. Together, these findings show that GSE targets both DNA damage and repair, and provide mechanistic insights for its efficacy selectively against HNSCC both in cell culture and mouse xenograft; supporting its translational potential against HNSCC.
