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Clin Cancer Res. 2006 Oct 1;12(19):5879-86.

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

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1
Institut National de la Santé et de la Recherche Médicale, E0211 Nutrition Croissance et Cancer, CHU Bretonneau, 2 bis Boulevard Tonnelle, F-37044 Tours, France.

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.

PMID:
17020996
DOI:
10.1158/1078-0432.CCR-06-0386
[Indexed for MEDLINE]
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