Asian Pacific Journal of Cancer Prevention

  • 제13권11호
  • /
  • Pages.5573-5579
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  • 2012
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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Inhibitory Effects of Onion (Allium cepa L.) Extract on Proliferation of Cancer Cells and Adipocytes via Inhibiting Fatty Acid Synthase

  • Wang, Yi (College of Life Sciences, University of Chinese Academy of Sciences) ;
  • Tian, Wei-Xi (College of Life Sciences, University of Chinese Academy of Sciences) ;
  • Ma, Xiao-Feng (College of Life Sciences, University of Chinese Academy of Sciences)
  • 발행 : 2012.11.30
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초록

Onions (Allium cepa L.) are widely used in the food industry for its nutritional and aromatic properties. Our studies showed that ethyl acetate extract of onion (EEO) had potent inhibitory effects on animal fatty acid synthase (FAS), and could induce apoptosis in FAS over-expressing human breast cancer MDA-MB-231 cells. Furthermore, this apoptosis was accompanied by reduction of intracellular FAS activity and could be rescued by 25 mM or 50 mM exogenous palmitic acids, the final product of FAS catalyzed synthesis. These results suggest that the apoptosis induced by EEO occurs via inhibition of FAS. We also found that EEO could suppress lipid accumulation during the differentiation of 3T3-L1 adipocytes, which was also related to its inhibition of intracellular FAS activity. Since obesity is closely related to breast cancer and obese patients are at elevated risk of developing various cancers, these findings suggested that onion might be useful for preventing obesity-related malignancy.

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참고문헌

  1. Alo PL, Amini M, Piro F, et al (2007). Immunohistochemical expression and prognostic significance of fatty acid synthase in pancreatic carcinoma. Anticancer Res, 27, 2523-27.
  2. Alo PL, Visca P, Marci A, et al (1996). Expression of fatty acid synthase (FAS) as a predictor of recurrence in stage I breast carcinoma patients. Cancer, 77, 474-82. https://doi.org/10.1002/(SICI)1097-0142(19960201)77:3<474::AID-CNCR8>3.0.CO;2-K
  3. Alo PL, Visca P, Trombetta G, et al (1999). Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas. Tumori, 85, 35-40.
  4. Arabbi PR, Genovese MI, Lajolo FM. (2004). Flavonoids in vegetable foods commonly consumed in Brazil and estimated ingestion by the Brazilian population. J Agr Food Chem, 52, 1124-31. https://doi.org/10.1021/jf0499525
  5. Block E (1985). The chemistry of garlic and onions. Sci Am, 252, 114-9.
  6. Caan BJ, Kwan ML, Hartzell G, et al (2008). Pre-diagnosis body mass index, post-diagnosis weight change, and prognosis among women with early stage breast cancer. Cancer Cause Control, 19, 1319-28. https://doi.org/10.1007/s10552-008-9203-0
  7. Calle EE, Rodriguez C, Walker-Thurmond K, et al (2003). Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. New Engl J Med, 348, 1625-38 https://doi.org/10.1056/NEJMoa021423
  8. Challier B, Perarnau JM, Viel JF. (1998). Garlic, onion and cereal fibre as protective factors for breast cancer: a French case-control study. Eur J Epidemiol, 14, 737-47. https://doi.org/10.1023/A:1007512825851
  9. Colditz GA (1992). Economic costs of obesity. Am J Clin Nutr, 55, S503-7. https://doi.org/10.1093/ajcn/55.2.503s
  10. Dawood S, Broglio K, Gonzalez-Angulo, et al (2008). Prognostic value of body mass index in locally advanced breast cancer. Clin Cancer Res, 14, 1718-25. https://doi.org/10.1158/1078-0432.CCR-07-1479
  11. Epstein JI, Carmichael M, Partin AW. (1995). OA-519 (fatty acid synthase) as an independent predictor of pathologic state in adenocarcinoma of the prostate. Urology, 45, 81-6. https://doi.org/10.1016/S0090-4295(95)96904-7
  12. Galeone C, Pelucchi C, Levi F, et al (2006). Onion and garlic use and human cancer. Am J Clin Nutr, 84, 1027-32. https://doi.org/10.1093/ajcn/84.5.1027
  13. Gansler TS, Hardman W, Hunt DA, et al (1997). Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival. Hum Pathol, 28, 686-92. https://doi.org/10.1016/S0046-8177(97)90177-5
  14. Hsing AW, Chokkalingam AP, Gao YT, et al (2002). Allium vegetables and risk of prostate cancer: A population-based study. J Natl Cancer I, 94, 1648-51. https://doi.org/10.1093/jnci/94.21.1648
  15. Khandekar MJ, Cohen P, Spiegelman BM. (2011). Molecular mechanisms of cancer development in obesity. Nature Rev Cancer, 11, 886-95 https://doi.org/10.1038/nrc3174
  16. Kim OY, Lee SM, Do H, et al (2012) Influence of quercetin-rich onion peel extracts on adipokine expression in the visceral adipose tissue of rats. Phytother Res, 26, 432-7.
  17. Kroenke CH, Chen WY, Rosner B, et al (2005). Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol, 23, 1370-8. https://doi.org/10.1200/JCO.2005.01.079
  18. Kuhajda FP. (2000). Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology. Nutrition, 16, 202-8. https://doi.org/10.1016/S0899-9007(99)00266-X
  19. Kuhajda FP. (2006). Fatty acid synthase and cancer: new application of an old pathway. Cancer Res, 66, 5977-80. https://doi.org/10.1158/0008-5472.CAN-05-4673
  20. Lahmann PH, Hoffmann K, Allen N, et al (2004). Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer, 111, 762-71. https://doi.org/10.1002/ijc.20315
  21. Le Bon AM, Siess MH. (2000). Organosulfur compounds from allium and the chemoprevention of cancer. Drug Metabol Drug Interact, 17, 51-79. https://doi.org/10.1515/DMDI.2000.17.1-4.51
  22. Lee KH, Kim Y, Park E, et al (2008). Effect of onion powder supplementation on lipid metabolism in high fat-cholesterol fed SD Rats. J Food Sci Nutr, 13, 1371-6.
  23. Lee SM, Moon J, Do HJ, et al (2012). Onion peel extract increases hepatic low-density lipoprotein receptor and ATPbinding cassette transporter A1 messenger RNA expressions in Sprague-Dawley rats fed a high-fat diet. Nutr Res, 32, 210-7. https://doi.org/10.1016/j.nutres.2012.01.004
  24. Lenhard JM. (2011). Lipogenic enzymes as therapeutic targets for obesity and diabetes. Curr Pharm Design, 17, 325-31. https://doi.org/10.2174/138161211795164185
  25. Menendez JA, Lupu R. (2007). Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis, Nature Rev Cancer, 7, 763-77. https://doi.org/10.1038/nrc2222
  26. Menendez JA, Mehmi I, Atlas E, et al (2004). Novel signaling molecules implicated in tumor-associated fatty acid synthase-dependent breast cancer cell proliferation and survival: Role of exogenous dietary fatty acids, p53-p21WAF1/CIP1, ERK1/2 MAPK, p27KIP1, BRCA1, and NF-kappaB. Int J Oncol, 24, 591-608.
  27. Milgraum LZ, Witters LA, Pasternack, GR, et al (1997). Enzymes of the fatty acid synthesis pathway are highly expressed in in situ breast carcinoma. Clin Cancer Res, 3, 2115-20.
  28. Orita H, Coulter J, Tully E, et al (2008). Inhibiting fatty acid synthase for chemoprevention of chemically induced lung tumors. Clin Cancer Res, 14, 2458-64. https://doi.org/10.1158/1078-0432.CCR-07-4177
  29. Pan SY, Johnson KC, Ugnat AM, et al (2004). Association of obesity and cancer risk in Canada. Am J Epidemiol, 159, 259-68. https://doi.org/10.1093/aje/kwh041
  30. Pizer ES, Lax SF, Kuhajda FP, et al (1998). Fatty acid synthase expression in endometrial carcinoma: correlation with cell proliferation and hormone receptors. Cancer, 83, 528-37. https://doi.org/10.1002/(SICI)1097-0142(19980801)83:3<528::AID-CNCR22>3.0.CO;2-X
  31. Pizer ES, Thupari J, Han WF, et al (2000). Malonyl-coenzymeA is a potential mediator of cytotoxicity induced by fattyacid synthase inhibition in human breast cancer cells and xenografts. Cancer Res, 60, 213-8.
  32. Prieto-Hontoria PL, Perez-Matute P, Fernandez-Galilea M, et al (2011). Role of obesity-associated dysfunctional adipose tissue in cancer: a molecular nutrition approach. BBA-Bioenergetics, 1807, 664-78. https://doi.org/10.1016/j.bbabio.2010.11.004
  33. Rashid A, Pizer ES, Moga M, et al (1997). Elevated expression of fatty acid synthase and fatty acid synthetic activity in colorectal neoplasia. Am J Pathol, 150, 201-8.
  34. Sengupta A, Ghosh S, Bhattacharjeethe S. (2004). Allium vegetables in cancer prevention: An overview. Asian Pac J Cancer Prev, 5, 237-45.
  35. Setiawan VW, Yu GP, Lu QY, et al (2005). Allium vegetables and stomach cancer risk in China. Asian Pac J Cancer Prev, 6, 387-95.
  36. Shurbaji MS, Kalbfleisch JH, Thurmond TS. (1996). Immunohistochemical detection of a fatty acid synthase (OA-519) as a predictor of progression of prostate cancer. Hum Pathol, 27, 917-21. https://doi.org/10.1016/S0046-8177(96)90218-X
  37. Soulie JM, Sheplock GJ, Tian WX, et al (1984). Transient kinetic studies of fatty acid synthetase. A kinetic self-editing mechanism for the loading of acetyl and malonyl residues and the role of coenzyme A. J Biol Chem, 259, 134-40.
  38. Sun XB, Tian WX. (2009). Inhibitory effects of Allium vegetable extracts on fatty acid synthase. Food Sci Technol Res, 15, 343-6. https://doi.org/10.3136/fstr.15.343
  39. Sung YY, Yoon T, Kim SJ, et al (2011). Anti-obesity activity of Allium fistulosum L. extract by down-regulation of the expression of lipogenic genes in high-fat diet-induced obese mice. Mol Med Report, 4, 431-5.
  40. Swinnen JV, Roskams T, Joniau S, et al (2002). Overexpression of fatty acid synthase is an early and common event in the development of prostate cancer. Int J Cancer, 98, 19-22. https://doi.org/10.1002/ijc.10127
  41. Tartter PI, Papatestas AE, Ioannovich J, et al (1981). Cholesterol and obesity as prognostic factors in breast cancer. Cancer, 47, 2222-7. https://doi.org/10.1002/1097-0142(19810501)47:9<2222::AID-CNCR2820470919>3.0.CO;2-5
  42. Tian WX, Hsu RY, Wang YS. (1985). Studies on the reactivity of the essential sulfhydryl groups as a conformational probe for the fatty acid synthetase of chicken liver. Inactivation by 5,5'-dithiobis-(2-nitrobenzoic acid) and intersubunit cross-linking of the inactivated enzyme. J Biol Chem, 260, 11375-87
  43. Uddin S, Ah-Kang J, Ulaszek J, et al (2004). Differentiation stage-specific activation of p38 mitogen-activated protein kinase isoforms in primary human erythroid cells. P Natl Acad Sci USA, 101, 147-52. https://doi.org/10.1073/pnas.0307075101
  44. van den Brandt PA, Spiegelman D, Yaun SS, et al (2000). Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol, 152, 514-27. https://doi.org/10.1093/aje/152.6.514
  45. Virtanen AL, Matikkala EJ. (1976). The isolation of S-methyl-Lcysteine sulphoxide and S-n-propyl-L-cysteine from onion (Allium cepa) and the antibiotic activity of crushed onion. Acta Chem Scand, 13, 1898-900.
  46. Visca P, Sebastiani V, Botti C, et al (2004). Fatty acid synthase (FAS) is a marker of increased risk of recurrence in lung carcinoma. Anticancer Res, 24, 4169-73.
  47. Walter K, Hong SM, Nyhan S, et al (2009). Serum fatty acid synthase as a marker of pancreatic neoplasia. Cancer Epidem Biomar, 18, 2380-5. https://doi.org/10.1158/1055-9965.EPI-09-0144
  48. Wang D, Dubois RN. (2012). Associations between obesity and cancer: the role of fatty acid synthase. J Natl Cancer I, 104, 343-5. https://doi.org/10.1093/jnci/djs010
  49. Zhou W, Simpson PJ, McFadden JM, et al (2003). Fatty acid synthase inhibition triggers apoptosis during S phase in human cancer cells. Cancer Res, 63, 7330-7.

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  11. Fresh-Cut Onion: A Review on Processing, Health Benefits, and Shelf-Life vol.17, pp.2, 2018, https://doi.org/10.1111/1541-4337.12331
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