ブドウの抽出物がガン細胞を破壊

 ブドウの種の抽出物(GSE)がガン細胞を破壊するとの米国からの報告。
 抽出物が白血病細胞が自滅することを刺激すると実験で確かめられた。24時間で76%の白血病細胞が死滅し、正常細胞は損傷を受けなかった。ガン治療の可能性があるが、予防するためにブドウの摂取が勧められるというには時期尚早である。
 以前の研究で、ブドウの種の抽出物が試験管レベルで皮膚、胸、腸、肺、胃、前立腺ガン細胞に効果あり。ラットの乳がん、マウスの皮膚がんに効果があった。今回のケンタッキー大学の研究報告で血液がんに効果があることが初めて示された。
 アポとーシスと呼ばれる細胞死の過程に作用して高い効果がある。損傷した危険な細胞を処理する自然な方法であり、このメカニズムが働かないとガン細胞が残存して増殖する事になる。アポトーシスを調節することに役立っているJNK(c-Jun NH2-terminal kinase)と呼ばれたたんぱく質を活性化するとわかった。白血病細胞をJNKを抑制する物質にさらすと、ブドウ種の抽出物の効果は相殺された。
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Page last updated at 07:42 GMT, Wednesday, 31 December 2008
Grape extract kills cancer cells
http://news.bbc.co.uk/2/hi/health/7803619.stm

画像Grapes
Grapes contain potentially beneficial chemicals

An extract from grape seeds can destroy cancer cells, US research suggests.

In lab experiments, scientists found that the extract stimulated leukaemia cells to commit suicide.
Within 24 hours, 76% of leukaemia cells exposed to the extract were killed off, while healthy cells were unharmed, Clinical Cancer Research reports.
The study raises the possibility of new cancer treatments, but scientists said it was too early to recommend that people eat grapes to ward off cancer.

What everyone seeks is an agent that has an effect on cancer cells but leaves normal cells alone, and this shows that grapeseed extract fits into this category
Professor Xianglin Shi
University of Kentucky
Grape seeds contain a number of antioxidants, including resveratrol, which is known to have anti-cancer properties, as well as positive effect on the heart.

Previous research has shown grapeseed extract has an effect on skin, breast, bowel, lung, stomach and prostate cancer cells in the laboratory.
It can also reduce the size of breast tumours in rats and skin tumours in mice.
However, the University of Kentucky study is the first to test its impact on a blood cancer.
Lead researcher Professor Xianglin Shi said: "These results could have implications for the incorporation of agents such as grapeseed extract into prevention or treatment of haematological (blood) malignancies and possibly other cancers.
"What everyone seeks is an agent that has an effect on cancer cells but leaves normal cells alone, and this shows that grapeseed extract fits into this category."
The researchers exposed leukaemia cells to grape extract in a range of different doses.

Apoptosis
One of the higher doses produced a marked effect, causing large numbers of the cells to commit suicide in a process known as apoptosis.
This is a natural method of getting rid of damaged and potentially dangerous cells.
When the mechanism behind apoptosis breaks down, cancerous cells can survive and multiply.
The researchers found grapeseed extract activates a protein called JNK which helps to regulate apoptosis.
When they exposed the leukaemia cells to an agent that inhibits JNK, the grapeseed extract effect was cancelled out.
Silencing the gene that makes JNK also blocked the extract's ability to kill cancer cells.
Kat Arney, Cancer Research UK's senior cancer information officer, warned against jumping to firm conclusions.
She said: "This is yet another story highlighting the potential cancer-fighting properties of naturally-occurring chemicals.
"Although interesting, it's still a long way from being a treatment that we can give to patients."

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Clinical Cancer Research 15, 140-149, January 1, 2009. doi: 10.1158/1078-0432.CCR-08-1447
© 2009 American Association for Cancer Research

Cancer Therapy: Preclinical
Induction of Apoptosis in Human Leukemia Cells by Grape Seed Extract Occurs via Activation of c-Jun NH2-Terminal Kinase
Ning Gao1,2, Amit Budhraja2, Senping Cheng2, Hua Yao2, Zhuo Zhang2 and Xianglin Shi2

Authors' Affiliations: 1 Department of Pharmacognosy, School of Pharmacy, 3rd Military Medical University, Chongqing, People's Republic of China and 2 Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, Kentucky

Requests for reprints: Xianglin Shi, Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536-0305. Phone: 859-257-4054; Fax: 859-323-1059; E-mail: xshi5@email.uky.edu.

Purpose: To characterize the functional role of c-Jun NH2-terminal kinase (JNK) and other apoptotic pathways in grape seed extract (GSE)-induced apoptosis in human leukemia cells by using pharmacologic and genetic approaches.

Experimental Design: Jurkat cells were treated with various concentrations of GSE for 12 and 24 h or with 50 µg/mL GSE for various time intervals, after which apoptosis, caspase activation, and cell signaling pathways were evaluated. Parallel studies were done in U937 and HL-60 human leukemia cells.

Results: Exposure of Jurkat cells to GSE resulted in dose- and time-dependent increase in apoptosis and caspase activation, events associated with the pronounced increase in Cip1/p21 protein level. Furthermore, treatment of Jurkat cells with GSE resulted in marked increase in levels of phospho-JNK. Conversely, interruption of the JNK pathway by pharmacologic inhibitor (e.g., SP600125) or genetic (e.g., small interfering RNA) approaches displayed significant protection against GSE-mediated lethality in Jurkat cells.

Conclusions: The result of the present study showed that GSE induces apoptosis in Jurkat cells through a process that involves sustained JNK activation and Cip1/p21 up-regulation, culminating in caspase activation.

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