This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Sauer, L. A. Articles by Scalici, S. Search for Related Content PubMed PubMed Citation Articles by Sauer, L. A. Articles by Scalici, S.

13-Hydroxyoctadecadienoic Acid Is the Mitogenic Signal for Linoleic Acid-dependent Growth in Rat Hepatoma 7288CTC in Vivo¹

Laboratory of Experimental Neuroendocrinology/Oncology, Bassett Research Institute, Cooperstown, New York 13326

Growth of hepatoma 7288CTC in male Buffalo rats is directly dependent on uptake of linoleic acid (LA) from the arterial blood. One to 5% of the LA taken up is converted to 13-hydroxyoctadecadienoic acid (HODE), an agent that enhances epidermal growth factor-dependent mitogenesis. The role of 13-HODE in LA-dependent growth of solid tumors is not known. In this study, we examined LA uptake and 13-HODE formation on growth of tissue-isolated hepatoma 7288CTC in vivo and on [³H] thymidine incorporation and DNA content during perfusion in situ. Fatty acid uptake and metabolite release were determined from arteriovenous difference measurements. Tumor-bearing and blood donor rats were fed either LA-sufficient or -deficient diets. Hepatoma 7288CTC removed LA from the arterial blood and released 13-HODE [and a small amount of 13-ketooctadecadienoic acid (KODE)] into the venous blood both in vivo and during perfusion. Treatment with the lipoxygenase inhibitor nordihydroguaiaretic acid (10 µM) did not affect tumor LA uptake, but inhibited release of 13-HODE and 13-KODE in vivo and during perfusion, suppressed growth in vivo, and inhibited [³H]thymidine incorporation during perfusion. The addition of 13-HODE to the nordihydroguaiaretic acid-containing whole blood perfusate increased the rate of [³H]thymidine incorporation 10 times and nearly doubled tumor DNA content; the addition of 13-KODE or 9-HODE had no effect. 13-HODE and 13-KODE were not released from tumors growing in rats fed a LA-deficient diet, and the rates of tumor growth in vivo and [³H]thymidine incorporation during perfusion were decreased. The addition of 13-HODE to the LA-deficient blood perfusate promoted tumor 13-HODE uptake and a dose-dependent increase in [³H]thymidine incorporation and tumor DNA content. These results provide strong evidence that 13-HODE is the mitogenic signal responsible for LA-dependent growth in hepatoma 7288CTC in vivo.

This article has been cited by other articles:

				V. Srinivasan, D W. Spence, S. R. Pandi-Perumal, I. Trakht, and D. P. Cardinali Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms Integr Cancer Ther, September 1, 2008; 7(3): 189 - 203. [Abstract] [PDF]

				L. A. Sauer, R. T. Dauchy, D. E. Blask, J. A. Krause, L. K. Davidson, and E. M. Dauchy Eicosapentaenoic Acid Suppresses Cell Proliferation in MCF-7 Human Breast Cancer Xenografts in Nude Rats via a Pertussis Toxin-Sensitive Signal Transduction Pathway J. Nutr., September 1, 2005; 135(9): 2124 - 2129. [Abstract] [Full Text] [PDF]

				L. A. Sauer, R. T. Dauchy, D. E. Blask, J. A. Krause, L. K. Davidson, E. M. Dauchy, K. J. Welham, and K. Coupland Conjugated Linoleic Acid Isomers and Trans Fatty Acids Inhibit Fatty Acid Transport in Hepatoma 7288CTC and Inguinal Fat Pads in Buffalo Rats J. Nutr., August 1, 2004; 134(8): 1989 - 1997. [Abstract] [Full Text] [PDF]

				D. E. Blask, R. T. Dauchy, L. A. Sauer, and J. A. Krause Melatonin uptake and growth prevention in rat hepatoma 7288CTC in response to dietary melatonin: melatonin receptor-mediated inhibition of tumor linoleic acid metabolism to the growth signaling molecule 13-hydroxyoctadecadienoic acid and the potential role of phytomelatonin Carcinogenesis, June 1, 2004; 25(6): 951 - 960. [Abstract] [Full Text] [PDF]

				A. W. Bull, K. R. Steffensen, J. Leers, and J. J. Rafter Activation of PPAR {gamma} in colon tumor cell lines by oxidized metabolites of linoleic acid, endogenous ligands for PPAR {gamma} Carcinogenesis, November 1, 2003; 24(11): 1717 - 1722. [Abstract] [Full Text] [PDF]

				D. Turgeon, S. Chouinard, P. Belanger, S. Picard, J.-F. Labbe, P. Borgeat, and A. Belanger Glucuronidation of arachidonic and linoleic acid metabolites by human UDP-glucuronosyltransferases J. Lipid Res., June 1, 2003; 44(6): 1182 - 1191. [Abstract] [Full Text] [PDF]

				U. P.Kelavkar, C. Cohen, H. Kamitani, T. E.Eling, and K. F.Badr Concordant induction of 15-lipoxygenase-1 and mutant p53 expression in human prostate adenocarcinoma: correlation with Gleason staging Carcinogenesis, October 1, 2000; 21(10): 1777 - 1787. [Abstract] [Full Text] [PDF]

				L. A. Sauer, R. T. Dauchy, and D. E. Blask Mechanism for the Antitumor and Anticachectic Effects of n-3 Fatty Acids Cancer Res., September 1, 2000; 60(18): 5289 - 5295. [Abstract] [Full Text]

				D. E. Blask, L. A. Sauer, R. T. Dauchy, E. W. Holowachuk, M. S. Ruhoff, and H. S. Kopff Melatonin Inhibition of Cancer Growth in Vivo Involves Suppression of Tumor Fatty Acid Metabolism via Melatonin Receptor-mediated Signal Transduction Events Cancer Res., September 1, 1999; 59(18): 4693 - 4701. [Abstract] [Full Text] [PDF]