Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines

被引:368
|
作者
Kuntz, S
Wenzel, U
Daniel, H
机构
[1] Inst Nutr Sci, D-85350 Freising Weihenstephan, Germany
[2] Inst Nutr Sci, D-35392 Giessen, Germany
关键词
flavonoids; cancer-cell lines; proliferation; cytotoxicity; apoptosis;
D O I
10.1007/s003940050054
中图分类号
R15 [营养卫生、食品卫生]; TS201 [基础科学];
学科分类号
100403 ;
摘要
Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Their proposed protective role in tumor development may prevail especially in the intestinal tract due to direct exposure of intestinal epithelia to these dietary ingredients. We have screened more than 30 flavonoids for their effects on cell proliferation and potential cytotoxicity in the human colon cancer cell lines Caco-2, displaying features of small intestinal epithelial cells, and HT-29, resembling colonic crypt cells. In addition, for selected compounds we assessed whether they induce apoptosis by determining caspase-3 activation. Studies on the dose dependent effects of the flavonoids showed antiproliferative activity of all compounds with EC50 values ranging between 39.7 +/- 2.3 mu M (baicalein) and 203.6 +/- 15.5 mu M (diosmin). In almost all cases, growth inhibition by the flavonoids occured in the absence of cytotoxicity. There was no obvious structure-activity relationship in the antiproliferative effects either on basis of the subclasses (i.e., isoflavones, flavones, flavonols, flavanones) or with respect to kind or position of substituents within a class. In a subset of experiments we examined the antiproliferative activities of the most potent compound of each flavonoid subgroup in addition in LLC-PK1, a renal tubular cell line, and the human breast cancer cell line MCF-7. Out of four flavonols tested, three displayed almost equal antiproliferative activities in all cell lines but fisetin was less potent in MCF-7 cells. The flavanones bavachinin and flavanone inhibited growth of Caco-2 and MT-29 cells with lower EC50 values than that obtained in LLC-PK1 and MCF-7 cells. The lower susceptibility of LLC-PK1 and MCF-7 cells towards growth arrest was even more pronounced in the case of the flavone baicalein, Half maximal growth-inhibition in LLC-PK1 and MCF-7 required 2.5 and 6.6 fold higher concentrations than that needed in the intestinal cell lines. The flavonoids failed to affect apoptosis in LLC-PK1 and MCF-7, whereas baicalein and myricetin were able to induce apoptosis in HT-29 and Caco-2 cells. In conclusion, flavonoids of the flavone, flavonol, flavanone, and isoflavone classes possess antiproliferative effects in different cancer cell lines. The capability of flavonoids for growth inhibition and induction of apoptosis can not be predicted on the basis of their chemical composition and structure.
引用
收藏
页码:133 / 142
页数:10
相关论文
共 50 条
  • [1] Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines
    S. Kuntz
    U. Wenzel
    H. Daniel
    European Journal of Nutrition, 1999, 38 : 133 - 142
  • [2] Effects of Scutellaria baicalensis and component flavonoids on apoptosis in colon cancer cell lines
    Harris, Diane
    Li, Luyi
    Heber, David
    Go, Vay Liang
    FASEB JOURNAL, 2007, 21 (05): : A361 - A362
  • [3] Comparative effects of RRR-alpha- and RRR-gamma-tocopherol on proliferation and apoptosis in human colon cancer cell lines
    Sharon E Campbell
    William L Stone
    Steven Lee
    Sarah Whaley
    Hongsong Yang
    Min Qui
    Paige Goforth
    Devin Sherman
    Derek McHaffie
    Koyamangalath Krishnan
    BMC Cancer, 6
  • [4] Comparative effects of RRR-alpha- and RRR-gamma-tocopherol on proliferation and apoptosis in human colon cancer cell lines
    Campbell, SE
    Stone, WL
    Lee, S
    Whaley, S
    Yang, HS
    Qui, M
    Goforth, P
    Sherman, D
    McHaffie, D
    Krishnan, K
    BMC CANCER, 2006, 6 (1)
  • [5] Involvement of PPARs in Cell Proliferation and Apoptosis in Human Colon Cancer Specimens and in Normal and Cancer Cell Lines
    Martinasso, G.
    Oraldi, M.
    Trombetta, A.
    Maggiora, M.
    Bertetto, O.
    Canuto, R. A.
    Muzio, G.
    PPAR RESEARCH, 2007, 2007
  • [6] Inhibition of Cell Proliferation and Induction of Apoptosis by Diallyl Disulfide in Human Colon Cancer Cell lines
    Kim, Tae Myoung
    Ryu, Jae Myun
    Kwon, Hyun Jung
    Woo, Koan Sik
    Jeong, Heon Sang
    Hong, Jin Tae
    Kim, Dae Joong
    TOXICOLOGICAL RESEARCH, 2005, 21 (04) : 355 - 360
  • [7] Effects of ascorbate on cell proliferation and apoptosis in human colon cancer cell lines, SW480 & HT-29
    Hong, TK
    Lee-Kim, YC
    FASEB JOURNAL, 2004, 18 (05): : A893 - A893
  • [8] Comparative Analysis of Acetylated Flavonoids' Chemopreventive Effects in Different Cancer Cell Lines
    Urakawa, Daigo
    Shioiridani, Yuki
    Igata, Shinya
    Hou, De-Xing
    Sakao, Kozue
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (14)
  • [9] Effect of parthenolide on proliferation and apoptosis in human colon cancer cell lines and in vivo tumor model
    Kim, S. W.
    Kim, H. I.
    Kim, S. H.
    Kim, I. H.
    Lee, S. O.
    Kim, D. G.
    Kim, S. L.
    Lee, S. T.
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2011, 26 : 222 - 223
  • [10] Effects of deoxycholate on human colon cancer cells: apoptosis or proliferation
    Milovic, V
    Teller, IC
    Faust, D
    Caspary, WF
    Stein, J
    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2002, 32 (01) : 29 - 34