2012年,，美國將會有差不多12000人死于頭頸部癌(head and neck cancer),，而在全世界,，人數(shù)將會超過50萬,。
2012年1月19日在線發(fā)表在Carcinogenesis期刊上的一項研究表明在細胞系和模式小鼠中,，葡萄籽抽提物(grape seed extract, GSE)殺死頭頸部鱗狀細胞癌細胞,，但同時不傷害健康細胞。
美國科羅拉多大學(xué)癌癥中心研究員Rajesh Agarwal博士,，也是史卡格斯制藥科學(xué)學(xué)院(Skaggs School of Pharmaceutical Sciences)的教授,，他說，“它產(chǎn)生極其大的影響”,。
Agarwal說,，它大部分上依賴于健康細胞等待傷害結(jié)束的能力。
Agarwal說,，“癌細胞是迅速生長的細胞,。不僅如此，它們必然是迅速生長的,。當它們不能生長的條件存在時,，它們就死亡。”
葡萄籽抽提物產(chǎn)生這些不適合癌細胞生長的條件,。特別地,，這篇論文表明葡萄籽抽提物(通過增加的活性氧)對癌細胞的DNA造成傷害，同時也阻止允許DNA修復(fù)的途徑(就像觀察到的DNA修復(fù)分子Brca1,、Rad51和DNA修復(fù)焦點的水平下降),。
Agarwal說，“但是我們完全沒有觀察到(葡萄籽抽提物)對小鼠本身有任何毒性,。”
在模式小鼠中,，葡萄籽抽提物再次只殺死癌細胞，而不殺死健康細胞,。
Agarwal說,，“我認為最重要的一點就是癌細胞擁有大量有缺陷的途徑，如果人們靶向這些途徑,，它們就變得非常脆弱,。但同樣的情況不適合于健康細胞。”
Agarwal實驗室希望葡萄籽抽提物進入臨床試驗,，潛在性地作為頭頸部鱗狀細胞癌在首次治療失敗后的二線治療,。(生物谷：towersimper編譯)
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.
