Abstract
We investigated the effects of cyclooxygenase and lipoxygenase inhibitors in the presence of linoleic acid (LA), as well as the direct effects of prostaglandin E (PGE) and leukotriene B (LTB) on a human breast cancer cell line (MDA-MB-231)in vitro. Piroxicam, esculetin, and nordihydroguaiaretic acid (NDGA) suppressed cell growth and thymidine incorporation. However, a low concentration (1 µg/ml) of indomethacin (INDO) stimulated cell growth and thymidine incorporation, while a high concentration of INDO (30 µg/ml) inhibited both. Esculetin and NDGA reduced the secretion of LTB, whereas piroxicam reduced the secretion of PGE. INDO reduced the secretion of PGE, but a low concentration of INDO increased the secretion of LTB. Consequently, cell growth was correlated with the PGE and/or LTB concentrations when the cells were treated with these cyclooxygenase or lipoxygenase inhibitors. On the other hand, exogenous PGE2 partially reversed the inhibition of thymidine incorporation caused by INDO, whereas LTB4 exerted a similar effect in the case of esculetin or NDGA. The reversibility of the piroxicam effect with PGE2 is not convincing. Therefore, it is suggested that the growth of MDA-MB-231 cellsin vitro is affected by both the lipoxygenase and cyclooxygenase products, probably the other eicosanoids rather than PGE2 and LTB4.
References
Hirayama T: Epidemiology of breast cancer with special reference to the role of diet. Prev Med 7: 173–195, 1978
Wynder EL, Rose DP, Cohen LA: Diet and breast cancer in causation and therapy. Cancer 58: 1804–1813, 1986
Hill P, Wynder EL: Comparison of mammary adipose fatty acid composition in Japanese and American breast cancer patients. Eur J Cancer Clin Oncol 23: 407–410, 1987
Welsch CW, Aylsworth CF: Enhancement of murine mammary tumorigenesis by feeding high levels of dietary fat: A hormonal mechanism? J Natl Cancer Inst 70: 215–221, 1983
Carter CA, Milholland RJ, Shea W, Ip MM: Effect of the prostaglandin synthetase inhibitor indomethacin on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats fed different levels of fat. Cancer Res 38: 3559–3562, 1983
McCormick DL, Madigan MJ, Moon RC: Modulation of rat mammary carcinogenesis by indomethacin. Cancer Res 45: 1803–1808, 1985
McCormick DL, Moon RC: Inhibition of mammary carcinogenesis by flurbiprofen, a non-steroidal anti-inflammatory agent. Br J Cancer 48: 859–861, 1983
Hillyard LA, Abraham S: Effect of dietary polyunsaturated fatty acids on growth of mammary adenocarcinomas in mice and rats. Cancer Res 39: 4430–4437, 1979
Fulton AM:In vivo effects of indomethacin on the growth of murine mammary tumors. Cancer Res 44: 2416–2420, 1984
Fulton AM, Heppner GH: Relationships of prostaglandin E and natural killer sensitivity to metastatic potential in murine mammary adenocarcinomas. Cancer Res 45: 4779–4784, 1985
Kollmorgen GM, King MM, Kosanke SD, Do C: Influence of dietary fat and indomethacin on the growth of transplantable mammary tumors in rats. Cancer Res 43: 4714–4719, 1983
Nagasawa H, Naito T: Inhibition by indomethacin of spontaneous mammary tumorigenesis in SHN mice. Breast Cancer Res Treat 8: 249–255, 1986
Hubbard NE, Chapkin RS, Erickson KL: Inhibition of growth and linoleate-enhanced metastasis of a transplantable mouse mammary tumor by indomethacin. Cancer Lett 43: 111–120, 1988
Carter CA, Ip MM, Ip C: A comparison of the effects of the prostaglandin synthesis inhibitors indomethacin and carprofen on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats fed different amounts of essential fatty acid. Carcinogenesis 10: 1369–1374, 1989
Feldman JM, Hill R: Failure of indomethacin to inhibit growth of the R3230 mammary tumor in rats. J Natl Cancer Inst 75: 751–756, 1985
Noguchi M, Taniya T, Koyasaki N, Kumaki T, Miyazaki I, Mizukami Y: Effects of the prostaglandin synthetase inhibitor indomethacin on tumorigenesis, tumor proliferation, cell kinetics, and receptor contents of 7,12-dimethylbenz(a) anthracene-induced mammary carcinoma in Spague-Dawley rats fed a high- or low-fat diet. Cancer Res 51: 2683–2689, 1991
Noguchi M, Ohta N: Influences of high dietary fat and/or indomethacin on tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in Sprague-Dawley rats. In Vivo 7: 53–58, 1993
Rose DP, Connolly JM: Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture. Cancer Res 50: 7139–7144, 1990
Buckman DK, Hubbard NE, Erickson KL: Eicosanoids and linoleate-enhanced growth of mouse mammary tumor cells. Prostaglandins Leukot Essent Fatty Acids 44: 177–184, 1991
Kitagawa H, Noguchi M: Comparative effects of piroxicam and esculetin on incidence, proliferation, and cell kinetics of mammary carcinomas induced by 7,12-dimethylbenz(a)anthracene in rats on high and low fat diets. Oncology 51: 401–410, 1994
Abou-El-Ela SH, Prasse KW, Farrell RL, Carroll RW, Wade AE, Bunce OR: Effects of D,L-2-difluoromethylornithine and indomethacin on mammary tumor promotion in rats fed high n-3 and/or n-6 fat diets. Cancer Res 49: 1434–1440, 1989
Mosmann T: Rapid colorimetric assay for cellular growth and survival. Application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55–63, 1983
Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB: Evaluation of a tetrazolium-based semiautomated colorimetric assay: Assessment of chemosensitivity testing. Cancer Res 47: 936–942, 1987
Carrol KK, Knor HT: Effects of dietary fat and dose level of 7,12-dimethylbenz(a)anthracene on mammary tumor incidence in rats. Cancer Res 30: 2260–2264, 1970
Hopkin GJ, West CE, Hard CC: Effect of dietary fats on the incidence of 7,12-dimethylbenz(a)anthracene-induced tumors in rats. Lipids 11: 328–333, 1976
Ip C: Ability of dietary fat to overcome the resistance of mature female rats to 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis. Cancer Res 40: 2785–2789, 1980
Aylsworth CF, Jone C, Trosko JE, Meites J, Welsch CW: Promotion of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis by high dietary fat in the rat: Possible role of intercellular communication. J Natl Cancer Inst 72: 637–645, 1984
Brunda MJ, Herberman RB, Holden HT: Inhibition of murine natural killer cell activity by prostaglandins. J Immunol 124: 2682–2687, 1980
Rolland PH, Martin PM, Jacquemier J, Rolland AM, Toga M: Prostaglandin production is a marker of high metastatic potential for neoplastic cells. J Natl Cancer Inst 64: 1061–1070, 1980
Karmali RA: Fatty acids: Inhibition. Am J Clin Nutr 45: 225–229, 1987
Karmali RA: Eicosanoids in neoplasia. Prev Med 16: 493–502, 1987
Lee PP, Ip MM: Regulation of proliferation of rat mammary tumor cells by inhibitors of cyclooxygenase and lipoxygenase. Prostaglandins Leukot Essent Fatty Acids 45: 21–31, 1992
Snyder DS, Castro R, Desforges JF: Antiproliferative effects of lipoxygenase inhibitors on malignant human hematopoietic cell lines. Exp Hematol 17: 6–9, 1989
Parker CW: Leukotrienes and prostaglandins in the immune system. In: Zor U, Naor Z, Kohen F (eds) Advances in Prostaglandin, Thromboxane and Leukotriene Research, Vol. 16. Raven Press, New York, 1986, pp 113–134
Earashi M, Noguchi M, Kinoshita K, Tanaka M: Effects of eicosanoid inhibitors on thein vitro growth and prostaglandin E and leukotriene B secretion of a human breast cancer cell line. Oncology 52: 150–155, 1995
Rose DP, Connolly JM: Stimulation of growth of human breast cancer cell lines in culture by linoleic acid. Biochem Biophys Res Commun 164: 277–283, 1989
Kidwell WR, Monaco ME, Wicha WS, Smith GS: Unsaturated fatty acid requirements for growth and survival of a rat mammary tumor cell line. Cancer Res 38: 4091–4100, 1978
Wicha MS, Liotta LA, Kidwell WR: Effects of free fatty acids on the growth of normal and neoplastic rat mammary epithelial cells. Cancer Res 39: 426–435, 1979
Vanderhoek JK, Ekborg SL, Bailey JM: Effects of cell growth, differentiation and transformation: Clinical involvement of leukotrienes. J Allergy Clin Immunol 74: 412–417, 1984
Fulton AM: Effects of indomethacin on the growth of cultured mammary tumors. Int J Cancer 33: 375–379, 1984
Bayer BM, Kruth HS, Vaughan M, Beaven MA: Arrest of cultured cells in the G1 phase of the cell cycle by indomethacin. J Pharmacol Exp Ther 210: 106–111, 1979
Hial V, DeMello MCF, Horakova Z, Beaven MA: Antiproliferative activity of anti-inflammatory drugs in two mammalian cell culture lines. J Pharmacol Exp Ther 202: 446–454, 1977
Hobbs DC: Pharmacokinetics of piroxicam in man. Eur J Rheum Inflamm 6: 46–55, 1983
Carty TJ, Stevens JS, Lombardino JG, Parry MJ, Randall MJ: Piroxicam, a structurally novel anti-inflammatory compound. Mode of prostaglandin synthesis inhibition. Prostaglandins 19: 671–682, 1980
Dahl SL, Ward JR: Pharmacology, clinical efficacy, and adverse effects of piroxicam, a new nonsteroidal anti-inflammatory agent. Pharmacotherapy 2: 80, 1982
Neichi T, Koshihara Y, Murota S: Inhibitory effect of esculetin on 5-lipoxygenase and leukotriene biosynthesis. Biochim Biophys Acta 753: 130–132, 1983
Maloff BL, Fefer D, Cooke GM, Ackerman NR: Inhibition of LTB4 binding to human neutrophils by nordihydroguaiaretic acid. Agents Action 21: 358–360, 1987
McCormick DL, Spicer AM: Nordihydroguaiaretic acid suppression of rat mammary carcinogenesis induced by Nmethyl-N-nitrosourea. Cancer Lett 37: 139–146, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Earashi, M., Noguchi, M. & Tanaka, M. In vitro effects of eicosanoid synthesis inhibitors in the presence of linoleic acid on MDA-MB-231 human breast cancer cells. Breast Cancer Res Tr 37, 29–37 (1996). https://doi.org/10.1007/BF01806629
Issue Date:
DOI: https://doi.org/10.1007/BF01806629