n-3 Polyunsaturated fatty acids decrease mucosal/epidermal reactions and enhance antitumour effect of ionising radiation with inhibition of tumour angiogenesis

Abstract

The purpose of this study was to evaluate the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on normal tissue (lip mucosa) and tumour growth when combined with ionising radiation. The oral region (snout) of C57 black mice was irradiated with 16.5 Gy and n-3 PUFAs (100 ml) were injected intravenously for 2 weeks. After exposure to irradiation, the degree and duration of the acute reactions decreased significantly when mice were treated with n-3 PUFAs as compared to the control group. Interestingly, the range of the reactions in the n-3 PUFAs-treated group compared favourably to the group receiving amifostine (27.5 mg/kg i.v.). the effect of n-3 PUFAs was further evaluated in HEP-2 human carcinoma xenograft transplanted in nude mice. An inhibition of tumour growth was observed when mice were treated with n-3 PUFAs alone and this effect was maximal when combined with irradiation. Similar results were obtained using eicosapentaenoic acid. The effect of n-3 PUFAs was associated with inhibition of angiogenesis and tumour proliferation, and significantly decreased expression of cyclooxygenase-2. In conclusion, n-3 PUFAs administration decrease mucosal response, while moderately enhancing the antitumour effect of irradiation. The magnitude of the differential effect suggests that n-3 PUFAs need to be further investigated in the clinic.

Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial

“…A slightly lower toxicity of chemotherapy with respect to anaemia and thrombopaenia was even observed in the H-DHA group. This is in line with the protective effects of DHA against the gastrointestinal toxicity of chemotherapy or radiation therapy in experimental models (Hardman et al, 1999;Kato et al, 2002;Wen et al, 2003;Xue et al, 2007) or in patients (Minami et al, 2008).…”

“…As DHA incorporates into cell membranes, this differential handling of ROS may account for the selectivity of DHA-induced tissue sensitisation by anti-cancer agents in tumour tissues compared with non-tumour tissues. Along this line, the lack of additional toxicity in non-tumour tissues has been consistently documented under conditions in which tumour tissue DHA was sensitised to chemotherapy (Hardman et al, 1999;Kato et al, 2002;Germain et al, 2003;Xue et al, 2007) or radiation therapy (Wen et al, 2003) in rodents.…”

Interaction of ω-3 polyunsaturated fatty acids with radiation therapy in two different colorectal cancer cell lines

“…14 The biochemical characteristics of u-3 PUFAs contributed to their different tumor-suppressive effects in breast cancer, which was proportional to their number of double bonds. 5 u-3 PUFAs increased the anti-tumor effect of RT in animal models of head and neck cancers 15 and mammary tumors. 16 RT is currently one of the main components of CRC treatment, especially for rectal cancer.…”

Sensitization by Dietary Docosahexaenoic Acid of Rat Mammary Carcinoma to Anthracycline: A Role for Tumor Vascularization

“…Moreover, these effects of n-3 PUFA were found to be suppressed by the presence of (3), and in vivo, in the presence of fish oil, dietary a-tocopherol decreased the efficacy of chemotherapy on mammary tumors (11). Similarly, the efficacy of radiation therapy, which generates ROS, was enhanced by n-3 PUFA both in vitro (12) or in vivo in mammary tumors (13) or in head and neck tumors (14). Therefore, the oxidative status, as well as the oxygen availability to the tumor, seems to be crucial determinants of its chemosensitivity or radiation sensitivity, stressing a role for tumor vascularization.…”