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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2012.1
- 수록면
- 470 - 476 (7page)
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초록· 키워드
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Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol ($100{\mu}M$) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells.
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참고문헌 (22)
참고문헌 신청
Apraiz, A. / 2012 / Dihydroceramide accumulation and reactive oxygen species are distinct and nonessential events in 4-HPR-mediated leukemia cell death / Biochem. Cell Biol 90:209~223
Aziz, M. H. / 2005 / Chemoprevention of skin cancer by grape constituent resveratrol: relevance to human disease? / FASEB J 19:1193~1195
Dudley, J. I. / 2008 / Does white wine qualify for French paradox? Comparison of the cardioprotective effects of red and white wines and their constituents: resveratrol, tyrosol, and hydroxytyrosol / J. Agric. Food Chem 56:9362~9373
Edsall, L. C. / 1998 / N,N-Dimethylsphingosine is a potent competitive inhibitor of sphingosine kinase but not of protein kinase C: modulation of cellular levels of sphingosine 1-phosphate and ceramide / Biochemistry 37:12892~12898
Fukui, M. / 2010 / Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells in vitro and in vivo / Eur. J. Cancer 46:1882~1891
Aziz, M. H. / 2005 / Chemoprevention of skin cancer by grape constituent resveratrol: relevance to human disease? / FASEB J 19:1193~1195
Dudley, J. I. / 2008 / Does white wine qualify for French paradox? Comparison of the cardioprotective effects of red and white wines and their constituents: resveratrol, tyrosol, and hydroxytyrosol / J. Agric. Food Chem 56:9362~9373
Edsall, L. C. / 1998 / N,N-Dimethylsphingosine is a potent competitive inhibitor of sphingosine kinase but not of protein kinase C: modulation of cellular levels of sphingosine 1-phosphate and ceramide / Biochemistry 37:12892~12898
Fukui, M. / 2010 / Resveratrol attenuates the anticancer efficacy of paclitaxel in human breast cancer cells in vitro and in vivo / Eur. J. Cancer 46:1882~1891
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