This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wenzel, U. Articles by Daniel, H. Search for Related Content PubMed PubMed Citation Articles by Wenzel, U. Articles by Daniel, H.

Dietary Flavone Is a Potent Apoptosis Inducer in Human Colon Carcinoma Cells

Institute of Nutritional Sciences, University of Giessen, 35392 Giessen [U. W., S. K., H. D.], and Third Department of Internal Medicine, University of Giessen, 35385 Giessen [M. D. B.], Germany

Flavonoids are polyphenolic compounds that occur ubiquitously in plants. They are discussed to represent cancer preventive food components in a human diet that is rich in fruits and vegetables. To understand the molecular basis of the putative anticancer activity of flavonoids, we investigated whether and how the core structure of the flavones, 2-phenyl-4H-1-benzopyran-4-one (flavone) affects proliferation, differentiation, and apoptosis in HT-29 human colon cancer cells. Moreover, the effects of flavone in transformed epithelial cells were compared with those obtained in nontransformed primary mouse colonocytes. Proliferation, differentiation, and apoptosis in transformed as well as nontransformed colon cells were measured by fluorescence-based techniques. Apoptosis was also determined by changes in membrane permeability, FACScan analysis, and detection of DNA fragmentation. Semiquantitative reverse transcription PCR was performed to assess the effects of flavone on transcript levels. Flavone was found to reduce cell proliferation in HT-29 cells with an EC₅₀ value of 54.8 ± 1.3 µM and to potently induce differentiation as well as apoptosis. The flavonoid proved to be a stronger apoptosis inducer than the clinically established antitumor agent camptothecin. The effects of flavone in HT-29 cells were associated with changed mRNA levels of cell-cycle- and apoptosis-related genes including cyclooxygenase-2 (COX-2), nuclear transcription factor B (NF-B), and bcl-X_L. Moreover, flavone, but not camptothecin, displayed a high selectivity for the induction of apoptosis and of growth inhibition only in the transformed colonocytes.

In conclusion, the plant polyphenol flavone induces effectively programmed cell death, differentiation, and growth inhibition in transformed colonocytes by acting at the mRNA levels of genes involved in these processes. Because these genes play a crucial role in colon carcinogenesis, flavone may prove to be a potent new cytostatic compound with improved selectivity toward transformed cells.

This article has been cited by other articles:

				Y.-H. CHANG, J.-S. YANG, J.-L. YANG, C.-L. WU, S.-J. CHANG, K.-W. LU, C.-L. KUO, T.-C. HSIA, and J.-G. CHUNG Gandoderma lucidum Extract Promotes Immune Responses in Normal BALB/c Mice In Vivo In Vivo, September 1, 2009; 23(5): 755 - 759. [Abstract] [Full Text] [PDF]

				T.-W. TAN, Y.-T. LIN, J.-S. YANG, C.-C. LU, J.-H. CHIANG, C.-L. WU, J.-P. LIN, N.-Y. TANG, C.-C. YEH, M.-J. FAN, et al. A. cantoniensis Inhibits the Proliferation of Murine Leukemia WEHI-3 Cells In Vivo and Promotes Immunoresponses In Vivo In Vivo, July 1, 2009; 23(4): 561 - 566. [Abstract] [Full Text] [PDF]

				S. J. Baek, M. F. McEntee, and A. M. Legendre REVIEW PAPER: Cancer Chemopreventive Compounds and Canine Cancer Vet. Pathol., July 1, 2009; 46(4): 576 - 588. [Abstract] [Full Text] [PDF]

				C.-C. HO, S.-Y. LIN, J.-S. YANG, K.-C. LIU, Y.-J. TANG, M.-D. YANG, J.-H. CHIANG, C.-C. LU, C.-L. WU, T.-H. CHIU, et al. Gallic Acid Inhibits Murine Leukemia WEHI-3 Cells In Vivo and Promotes Macrophage Phagocytosis In Vivo, May 1, 2009; 23(3): 409 - 413. [Abstract] [Full Text] [PDF]

				D. A. Oyugi, X. Luo, K. S. Lee, B. Hill, and E. B. Izevbigie Activity Markers of the Anti-Breast Carcinoma Cell Growth Fractions of Vernonia amygdalina Extracts Experimental Biology and Medicine, April 1, 2009; 234(4): 410 - 417. [Abstract] [Full Text] [PDF]

				I. Winkelmann, D. Diehl, D. Oesterle, H. Daniel, and U. Wenzel The suppression of aberrant crypt multiplicity in colonic tissue of 1,2-dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes Carcinogenesis, July 1, 2007; 28(7): 1446 - 1454. [Abstract] [Full Text] [PDF]

				R. Feng, H.-M. Ni, S. Y. Wang, I. L. Tourkova, M. R. Shurin, H. Harada, and X.-M. Yin Cyanidin-3-rutinoside, a Natural Polyphenol Antioxidant, Selectively Kills Leukemic Cells by Induction of Oxidative Stress J. Biol. Chem., May 4, 2007; 282(18): 13468 - 13476. [Abstract] [Full Text] [PDF]

				J. Lin, S. M. Zhang, K. Wu, W. C. Willett, C. S. Fuchs, and E. Giovannucci Flavonoid Intake and Colorectal Cancer Risk in Men and Women Am. J. Epidemiol., October 1, 2006; 164(7): 644 - 651. [Abstract] [Full Text] [PDF]

				P. A. Ruiz and D. Haller Functional Diversity of Flavonoids in the Inhibition of the Proinflammatory NF-{kappa}B, IRF, and Akt Signaling Pathways in Murine Intestinal Epithelial Cells J. Nutr., March 1, 2006; 136(3): 664 - 671. [Abstract] [Full Text] [PDF]

				P. C. Karlsson, U. Huss, A. Jenner, B. Halliwell, L. Bohlin, and J. J. Rafter Human Fecal Water Inhibits COX-2 in Colonic HT-29 Cells: Role of Phenolic Compounds J. Nutr., October 1, 2005; 135(10): 2343 - 2349. [Abstract] [Full Text] [PDF]

				S. R. Volate, D. M. Davenport, S. J. Muga, and M. J. Wargovich Modulation of aberrant crypt foci and apoptosis by dietary herbal supplements (quercetin, curcumin, silymarin, ginseng and rutin) Carcinogenesis, August 1, 2005; 26(8): 1450 - 1456. [Abstract] [Full Text] [PDF]

				U. Wenzel, A. Nickel, and H. Daniel Increased Carnitine-Dependent Fatty Acid Uptake into Mitochondria of Human Colon Cancer Cells Induces Apoptosis J. Nutr., June 1, 2005; 135(6): 1510 - 1514. [Abstract] [Full Text] [PDF]

				S. J. Baek, J.-S. Kim, F. R. Jackson, T. E. Eling, M. F. McEntee, and S.-H. Lee Epicatechin gallate-induced expression of NAG-1 is associated with growth inhibition and apoptosis in colon cancer cells Carcinogenesis, December 1, 2004; 25(12): 2425 - 2432. [Abstract] [Full Text] [PDF]

				S. G.J. van Breda, E. van Agen, L. G.J.B. Engels, E. J.C. Moonen, J. C.S. Kleinjans, and J. H.M. van Delft Altered vegetable intake affects pivotal carcinogenesis pathways in colon mucosa from adenoma patients and controls Carcinogenesis, November 1, 2004; 25(11): 2207 - 2216. [Abstract] [Full Text] [PDF]

				U. Wenzel, A. Nickel, S. Kuntz, and H. Daniel Ascorbic acid suppresses drug-induced apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions Carcinogenesis, May 1, 2004; 25(5): 703 - 712. [Abstract] [Full Text] [PDF]

				B. Kindermann, F. Doring, M. Pfaffl, and H. Daniel Identification of Genes Responsive to Intracellular Zinc Depletion in the Human Colon Adenocarcinoma Cell Line HT-29 J. Nutr., January 1, 2004; 134(1): 57 - 62. [Abstract] [Full Text] [PDF]

				U. Wenzel, S. Kuntz, and H. Daniel Nitric Oxide Levels in Human Preneoplastic Colonocytes Determine Their Susceptibility toward Antineoplastic Agents Mol. Pharmacol., December 1, 2003; 64(6): 1494 - 1502. [Abstract] [Full Text] [PDF]

				J Schauber, C Svanholm, S Termen, K Iffland, T Menzel, W Scheppach, R Melcher, B Agerberth, H Luhrs, and G H Gudmundsson Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways Gut, May 1, 2003; 52(5): 735 - 741. [Abstract] [Full Text]

				K. W. Kang, E. Y. Park, and S. G. Kim Activation of CCAAT/enhancer-binding protein {beta} by 2'-amino-3'-methoxyflavone (PD98059) leads to the induction of glutathione S-transferase A2 Carcinogenesis, March 1, 2003; 24(3): 475 - 482. [Abstract] [Full Text] [PDF]

				M.-H. Pan, W.-J. Chen, S.-Y. Lin-Shiau, C.-T. Ho, and J.-K. Lin Tangeretin induces cell-cycle G1 arrest through inhibiting cyclin-dependent kinases 2 and 4 activities as well as elevating Cdk inhibitors p21 and p27 in human colorectal carcinoma cells Carcinogenesis, October 1, 2002; 23(10): 1677 - 1684. [Abstract] [Full Text] [PDF]

				R. P. Singh, A. K. Tyagi, J. Zhao, and R. Agarwal Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis Carcinogenesis, March 1, 2002; 23(3): 499 - 510. [Abstract] [Full Text] [PDF]

				C Bojarski, A H Gitter, K Bendfeldt, J Mankertz, H Schmitz, S Wagner, M Fromm, and J D Schulzke Permeability of human HT-29/B6 colonic epithelium as a function of apoptosis J. Physiol., September 1, 2001; 535(2): 541 - 552. [Abstract] [Full Text] [PDF]