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Sensitization by dietary docosahexaenoic acid of rat mammary carcinoma to anthracycline: a role for tumor vascularization.

Abstract : PURPOSE: To investigate whether dietary docosahexaenoic acid (DHA), a peroxidizable polyunsaturated omega-3 fatty acids, sensitizes rat mammary tumors to anthracyclines and whether its action interferes with tumor vascularization, a critical determinant of tumor growth. EXPERIMENTAL DESIGN: Female Sprague-Dawley rats were initiated by N-methylnitrosourea to develop mammary tumors and then assigned to a control group (n = 18), receiving a supplementation of palm oil, or to a DHA group (n = 54), supplemented with a microalgae-produced oil (DHASCO, 1.5 g/d). The DHA group was equally subdivided into three subgroups with addition of different amounts of alpha-tocopherol. Epirubicin was injected weekly during 6 weeks after the largest tumor reached 1.5 cm(2), and subsequent changes in the tumor surface were evaluated. Tumor vascularization was assessed by power Doppler sonography before and during chemotherapy. RESULTS: DHA and alpha-tocopherol were readily absorbed and incorporated into rat tissues. Epirubicin induced a 45% mammary tumor regression in the DHA-supplemented group, whereas no tumor regression was observed in the control group. In the DHA group, before chemotherapy was initiated, tumor vascular density was 43% lower than in the control group and remained lower during chemotherapy. Enhancement of epirubicin efficacy by DHA was abolished in a dose-dependent manner by alpha-tocopherol, and the same trend was observed for DHA-induced reduction in tumor vascular density. CONCLUSIONS: Dietary DHA supplementation led to a reduction in tumor vascularization before the enhancement of any response to anthracyclines, suggesting that DHA chemosensitizes mammary tumors through an inhibition of the host vascular response to the tumor.
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Contributor : Philippe Bougnoux <>
Submitted on : Sunday, January 14, 2007 - 5:25:37 PM
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Séverine Colas, Karine Mahéo, Fabrice Denis, Caroline Goupille, Claude Hoinard, et al.. Sensitization by dietary docosahexaenoic acid of rat mammary carcinoma to anthracycline: a role for tumor vascularization.. Clinical Cancer Research, American Association for Cancer Research, 2006, 12 (19), pp.5879-86. ⟨10.1158/1078-0432.CCR-06-0386⟩. ⟨inserm-00124363⟩



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