The citrus flavonoid nobiletin inhibits proliferation and induces apoptosis in human pancreatic cancer cells in vitro

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• 作者：Yu Zhang (1) (2)
  Huating Dou (2)
  Hongjun Li (1)
  Zhifei He (1)
  Houjiu Wu (2)
  
• 关键词：nobiletin ; pancreatic cancer ; cell proliferation ; apoptosis ; cell cycle
• 刊名：Food Science and Biotechnology
• 出版年：2014
• 出版时间：February 2014
• 年：2014
• 卷：23
• 期：1
• 页码：225-229
• 全文大小：283 KB
• 参考文献：1. Jemal A, Siegel R, Ward E, Hao YP, Xu JQ, Michael J. Cancer statistics. CA-Cancer J. Clin. 59:225鈥?49 (2009) CrossRef
  2. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics. CA-Cancer J. Clin. 60:277鈥?00 (2010) CrossRef
  3. Guo X, Cui Z. Current diagnosis and treatment of pancreatic cancer in China. Pancreas 31:13鈥?2 (2005) CrossRef
  4. Ardeesy N, DePinho RA. Pancreatic cancer biology and genetics. Nat. Rev. Cancer 2:897鈥?09 (2002) CrossRef
  5. Inoue T, Tsubaki S, Ogawa K, Onishi K, Azuma J. Isolation of hesperidin from peels of thinned / Citrus unshiu fruits by microwaveassisted extraction. Food Chem. 123:542鈥?47 (2010) CrossRef
  6. He L, Gongke L, Zhanxia Z. Effects of operating parameters on the extraction of resveratrol in Huzhang ( / Polygonum cuspidatum) using microwave-assisted extraction. Chinese J. Anal. Chem. 31:1341鈥?344 (2003)
  7. Zhilu A, Juan G, Yuhong W, Yanxia L, Qiuyan Z. Microwaveassisted extraction technique of apple polyphenols in apple pomace. T. Chinese Soc. Agr. Eng. 6:188鈥?91 (2006)
  8. Min X, Lu W. Study on extraction of cordycepin with microwave. Food Sci. 10:248鈥?51 (2006)
  9. Mouly PP, Gaydou EM, Aazouyan C. Separation and quantitation of orange juices using liquid chromatography of polymethoxylated flavones. Analusis 27:284鈥?88 (1999) CrossRef
  10. Delaney B, Phillps K, Vasquez C, Wilson A, Cox D, Wang HB, Manthey J. Genetic toxieity of astandardized mixture of citrus polymethoxylated flavones. Food Chem Toxicol. 40:617鈥?24 (2002) CrossRef
  11. Delaney B, Phillip K, Buswell D, Mowry B, Nickels D, Cox D, Wang HB, Manthey J. Immunotoxicity of a standardized citrus polymethoxylated flavone extract. Food Chem. Toxicol. 39:1087鈥?094 (2001) CrossRef
  12. Manthey JA, Grohmann K. Phenols in citrus peel by products concentrations of hydroxycinnamates and polylmethoxylated flavones in citrus peel molasses. J. Agr. Food Chem. 49:3268鈥?273 (2001) CrossRef
  13. Londono-Londono J, De Lima V, Lara O, Gil A, Cresynski Pasa TB, Arango GJ, Pineda JR. Clean recovery of antioxidant flavonoids from citrus peel: Optimizing an aqueous ultrasoundassisted extraction method. Food Chem. 119:81鈥?7 (2010) CrossRef
  14. Waldman T, Zhang Y, Dillehay L, Yu J, Kinzler K, Vogelstein B, Williams J. Cell-cycle arrest versus cell death in cancer therapy. Nat. Med. 3:1034鈥?036 (1997) CrossRef
  15. Akao Y, Ohguchi K, Iinuma M, Nozawa Y. Interactive effects of polymethoxy flavones from citrus on cell growth inhibition in human neuroblastoma SH-SY5Y cells. Bioorgan. Med. Chem. 16:2803鈥?810 (2008) CrossRef
  16. Androutsopoulos VP, Surichan S, Arroo RRJ, Boarder MR. Citrus flavonoid nobiletin induces CVP1-enzyme activity and CYP1-mediated oxidative metabolism in MCF-7 breast adenocarcinoma cells. Int. J. Mol. Med. 26:S52鈥揝52 (2010)
  17. Lee YC, Cheng TH, Lee JS, Chen JH, Liao YC, Fong Y, Wu CH, Shih YW. Nobiletin, a citrus flavonoid, suppresses invasion and migration involving FAK/PI3K/Akt and small GTPase signals in human gastric adenocarcinoma AGS cells. Mol. Cell Biochem. 347:103鈥?15 (2011) CrossRef
  18. Miyata Y, Sato T, Imada K, Dobashi A, Yano M, Ito A. A citirus polymethoxyflavonoid, nobiletin, is a novel MEK inhibitor that exhibits antitumor metastasis in human fibrosarcoma HT-1080 cells. Biochem. Bioph. Res. Co. 366:168鈥?73 (2008) CrossRef
  19. Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchel JB. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer. Res. 47:943鈥?46 (1987)
  20. Burlacu A. Regulation of apoptosis by bcl-2 family proteins. J. Cell Mol. Med. 7:249鈥?57 (2003) CrossRef
  21. Cory S, Adams JM. The bcl-2 family: Regulators of the cellular life-or-death switch. Nat. Rev. Cancer. 2:647鈥?56 (2002) CrossRef
  22. Kuwana T, Mackey MR, Perkins G. Ellisman MH, Latterich M, Schneiter R, Green DR, Newmeyer DD. Bid, bax, and lipids cooperate to form supramolecular openings in the outer mitochondrial membrane. Cell 111:331鈥?42 (2002) CrossRef
  23. Del Poeta G, Venditti A, Del Principe MI, Maurillo L, Buccisano F, Tamburini A, Cox MC, Franchi A, Bruno A, Mazzone C, Panetta P, Suppo G, Masi M, Amadori S. Amount of spontaneous apoptosis detected by bax/bcl-2 ratio predicts outcome in acute myeloid leukemia (amL). Blood 101:2125鈥?131 (2003) CrossRef
  24. Pietenpol JA, Stewart ZA. Cell cycle checkpoint signaling: cell cycle arrest versus apoptosis. Toxicology 12:475鈥?81 (2002) CrossRef
  25. Chan KT, Meng FY, Li Q, Ho CY, Lam TS, To Y, Lee WH, Li M, Chu KH, Toh M. Cucurbitacin B induces apoptosis and S phase cell cycle arrest in BEL-7402 human hepatocellular carcinoma cells and is effective via oral administration. Cancer Lett. 294:118鈥?24 (2010) CrossRef
  26. Shen JK, Du HP, Yang M, Wang YG, Jin J. Casticin induces leukemic cell death through apoptosis and mitotic catastrophe. Ann. Hematol. 88:743鈥?52 (2009) CrossRef
  27. Ding C, Khan M, Zheng B, Yang JB, Zhong LL, Ma TH. Casticin induces apoptosis and mitotic arrest in pancreatic carcinoma PANC-1 cells. Afr. J. Pharm. Pharmaco. 6:412鈥?18 (2012)
  28. Qi X, Zhang DR, Xu X, Feng FF, Ren GJ, Chu QQ, Zhang Q, Tian K. Oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line. Int. J. Nanomed. 7:1793鈥?804 (2012)
  29. Li W, Xie L, Chen Z, Zhu Y, Sun YJ, Miao Y, Xu ZK, Han X. Cantharidin, a potent and selective PP2A inhibitor, induces an oxidative stressindependent growth inhibition of pancreatic cancer cells through G2/M cellcycle arrest and apoptosis. Cancer Sci. 101:1226鈥?233 (2010) CrossRef
  30. El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell 75:817鈥?25 (1993) CrossRef
  
• 作者单位：Yu Zhang (1) (2)
  Huating Dou (2)
  Hongjun Li (1)
  Zhifei He (1)
  Houjiu Wu (2)
  
  1. College of Food Science, Southwest University, Chongqing, 400716, China
  2. Citrus Research Institute, Chinese Academy of Agricultural Sciences, Southwest University, Chongqing, 400712, China
  
• ISSN：2092-6456

文摘

The cellular effects of nobiletin on human pancreatic cancer cells (PANC-1) and the mechanisms by which nobiletin inhibits the proliferation of these cells were investigated. A MTT assay and flow cytometry were used to examine cell proliferation and apoptosis, respectively. A Western blot assay was used to examine expression levels of the apoptotic proteins bax, bcl-2, and p53. NOB induced apoptosis in these cells via up-regulation of the proapoptotic protein bax and down-regulation of the antiapoptotic proteins bcl-2 and p53. The normal cell cycle of PANC-1 cells was arrested by NOB with a significant increase in the proportion of G0/G1 phase cells (p<0.05) and a significant decrease in the proportion of S phase cells (p<0.05). NOB can inhibit the proliferation of human pancreatic carcinoma cells by inducing apoptosis and arresting the cell cycle progression.