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


METHODS
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.
Colas
Séverine
S
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.
Mahéo
Karine
K
Denis
Fabrice
F
Goupille
Caroline
C
Hoinard
Claude
C
Champeroux
Pascal
P
Tranquart
François
F
Bougnoux
Philippe
P
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000008:administration & dosage*; D015251:Epirubicin / Q000494:pharmacology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000276:immunology; D008770:Methylnitrosourea / Q000633:toxicity; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage
D000477:Alkylating Agents; D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D004281:Docosahexaenoic Acids; D015251:Epirubicin; D008770:Methylnitrosourea; D024502:alpha-Tocopherol