Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Dec;62(6):942–946. doi: 10.1038/bjc.1990.414

Inhibitory effect of quercetin on OVCA 433 cells and presence of type II oestrogen binding sites in primary ovarian tumours and cultured cells.

G Scambia 1, F O Ranelletti 1, P B Panici 1, M Piantelli 1, G Bonanno 1, R De Vincenzo 1, G Ferrandina 1, C Rumi 1, L M Larocca 1, S Mancuso 1
PMCID: PMC1971559  PMID: 2257224

Abstract

We investigated the effect of the flavonoid quercetin (Q) on the proliferation of the ovarian cancer cell line OVCA 433. Growth experiments demonstrated that Q exerted a reversible dose-dependent inhibition of cell proliferation in the range of concentrations between 10 nM and 10 microM. Two other flavonoids tested, rutin and hesperidin, were ineffective in inhibiting cell growth. Cell cycle analysis showed that the growth inhibitory effect of Q was due to a blocking effect in the GO/G1 phase. Using a whole cell assay with (6.7-3H) oestradiol (3H-E2) as tracer we demonstrated that OVCA 433 cells contain type II oestrogen binding sites (type II EBS). Competition analysis showed that Q competed for 3H-E2 binding to type II EBS while both rutin and hesperidin did not. Appreciable amounts of type II EBS were also detected in seven primary ovarian tumours. Our results suggest that Q may regulate ovarian cancer cell growth through a mechanism involving a binding interaction with type II EBS. This mechanism could also be active in vivo since primary ovarian tumours contain type II EBS.

Full text

PDF
942

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  2. Bustamante E., Pedersen P. L. High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3735–3739. doi: 10.1073/pnas.74.9.3735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang R. L., Huang M. T., Wood A. W., Wong C. Q., Newmark H. L., Yagi H., Sayer J. M., Jerina D. M., Conney A. H. Effect of ellagic acid and hydroxylated flavonoids on the tumorigenicity of benzo[a]pyrene and (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene on mouse skin and in the newborn mouse. Carcinogenesis. 1985 Aug;6(8):1127–1133. doi: 10.1093/carcin/6.8.1127. [DOI] [PubMed] [Google Scholar]
  4. Clark J. H., Hardin J. W., Upchurch S., Eriksson H. Heterogeneity of estrogen binding sites in the cytosol of the rat uterus. J Biol Chem. 1978 Nov 10;253(21):7630–7634. [PubMed] [Google Scholar]
  5. Graziani Y. Bioflavonoid regulation of ATPase and hexokinase activity in Ehrlich ascites cell mitochondria. Biochim Biophys Acta. 1977 May 11;460(2):364–373. doi: 10.1016/0005-2728(77)90221-3. [DOI] [PubMed] [Google Scholar]
  6. Graziani Y., Erikson E., Erikson R. L. The effect of quercetin on the phosphorylation activity of the Rous sarcoma virus transforming gene product in vitro and in vivo. Eur J Biochem. 1983 Oct 3;135(3):583–589. doi: 10.1111/j.1432-1033.1983.tb07692.x. [DOI] [PubMed] [Google Scholar]
  7. Gugler R., Leschik M., Dengler H. J. Disposition of quercetin in man after single oral and intravenous doses. Eur J Clin Pharmacol. 1975 Dec 19;9(2-3):229–234. doi: 10.1007/BF00614022. [DOI] [PubMed] [Google Scholar]
  8. Hoffman R., Graham L., Newlands E. S. Enhanced anti-proliferative action of busulphan by quercetin on the human leukaemia cell line K562. Br J Cancer. 1989 Mar;59(3):347–348. doi: 10.1038/bjc.1989.68. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kuriki Y., Racker E. Inhibition of (Na+, K+)adenosine triphosphatase and its partial reactions by quercetin. Biochemistry. 1976 Nov 16;15(23):4951–4956. doi: 10.1021/bi00668a001. [DOI] [PubMed] [Google Scholar]
  10. Markaverich B. M., Roberts R. R., Alejandro M. A., Clark J. H. An endogenous inhibitor of [3H]estradiol binding to nuclear type II estrogen binding sites in normal and malignant tissues. Cancer Res. 1984 Apr;44(4):1515–1519. [PubMed] [Google Scholar]
  11. Markaverich B. M., Roberts R. R., Finney R. W., Clark J. H. Preliminary characterization of an endogenous inhibitor of [3H]estradiol binding in rat uterine nuclei. J Biol Chem. 1983 Oct 10;258(19):11663–11671. [PubMed] [Google Scholar]
  12. Markaverich B. M., Williams M., Upchurch S., Clark J. H. Heterogeneity of nuclear estrogen-binding sites in the rat uterus: a simple method for the quantitation of type I and type II sites by [3H]estradiol exchange. Endocrinology. 1981 Jul;109(1):62–69. doi: 10.1210/endo-109-1-62. [DOI] [PubMed] [Google Scholar]
  13. Monahan T. M., Marchand N. W., Fritz R. R., Abell C. W. Cyclic adenosine 3':5'-monophosphate levels and activities of related enzymes in normal and leukemic lymphocytes. Cancer Res. 1975 Sep;35(9):2540–2547. [PubMed] [Google Scholar]
  14. Nakadate T., Yamamoto S., Aizu E., Kato R. Effects of flavonoids and antioxidants on 12-O-tetradecanoyl-phorbol-13-acetate-caused epidermal ornithine decarboxylase induction and tumor promotion in relation to lipoxygenase inhibition by these compounds. Gan. 1984 Mar;75(3):214–222. [PubMed] [Google Scholar]
  15. Nishino H., Nagao M., Fujiki H., Sugimura T. Role of flavonoids in suppressing the enhancement of phospholipid metabolism by tumor promoters. Cancer Lett. 1983 Nov;21(1):1–8. doi: 10.1016/0304-3835(83)90075-7. [DOI] [PubMed] [Google Scholar]
  16. Nishino H., Naito E., Iwashima A., Tanaka K., Matsuura T., Fujiki H., Sugimura T. Interaction between quercetin and Ca2+-calmodulin complex: possible mechanism for anti-tumor-promoting action of the flavonoid. Gan. 1984 Apr;75(4):311–316. [PubMed] [Google Scholar]
  17. Ranelletti F. O., Piantelli M., Carbone A., Rinelli A., Scambia G., Panici P. B., Mancuso S. Type II estrogen-binding sites and 17 beta-hydroxysteroid dehydrogenase activity in human peripheral blood mononuclear cells. J Clin Endocrinol Metab. 1988 Nov;67(5):888–892. doi: 10.1210/jcem-67-5-888. [DOI] [PubMed] [Google Scholar]
  18. Shoshan V., MacLennan D. H. Quercetin interaction with the (Ca2+ + Mg2+)-ATPase of sarcoplasmic reticulum. J Biol Chem. 1981 Jan 25;256(2):887–892. [PubMed] [Google Scholar]
  19. Verma A. K., Johnson J. A., Gould M. N., Tanner M. A. Inhibition of 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced rat mammary cancer by dietary flavonol quercetin. Cancer Res. 1988 Oct 15;48(20):5754–5758. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES