Fish oil supplementation enhanced CPT-11 (irinotecan) efficacy against MCF7 breast carcinoma xenografts and ameliorated intestinal side-effects

Abstract

SummaryThe cancer chemotherapeutic efficacy of the topoisomerase I inhibitor, is often limited by the induction of severe delayed diarrhoea. In animal studies, CPT-11 use is associated with histopathological damage to the mucosa of the small and large intestines. Results from the present study demonstrate that 60 mg CPT-11 per kg body weight (i.v. q4d ϫ 6) halted the growth, but did not cause significant regression, of MCF7 human breast carcinoma xenografts in mice fed a diet containing 7% corn oil. However, when the diet of the MCF7-bearing mice was supplemented with 3% or 6% fish oil, the same CPT-11 treatment caused significant regression of the MCF7 xenograft. Histomorphometric analyses of intestinal mucosa of mice treated with CPT-11 and fed the diet containing 7% corn oil indicated that treatment with CPT-11 induced structural changes in the intestinal mucosa which persisted at least 5 days after the last dose of CPT-11. The intestinal mucosal architecture of mice that were treated with CPT-11 and fed the diets containing fish oil was largely unchanged from the architecture of the group of mice which did not receive CPT-11. These findings indicate that fish oil supplements may be a useful adjunct to CPT-11 treatment.

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.…”

Consumption of an omega-3 fatty acids product, INCELL AAFA™, reduced side-effects of CPT-11 (irinotecan) in mice

“…Thus 2% AAFA TM in the diet reduced the side effects of CPT-11 treatment in mice. We have reported that supplementing the diet of mice with fish oil increased the efficacy of edelfosine against MDA-MB 231 human breast cancer (Hardman et al, 1997), doxorubicin against A549 human lung cancer (Hardman et al, 2000) and CPT-11 against MCF-7 human breast cancer (Hardman et al, 1999a). Other investigators have found that supplementing the diet with omega-3 fatty acids increased the efficacy of: epirubicin against rat mammary tumours (Germain et al, 1999) and cyclophosphamide (Shao et al, 1997) or mitomycin (Shao et al, 1995) against MX-1 human mammary tumours.…”

“…The results of in vitro studies have shown that a small amount of either eicosapentaenoic acid (EPA) or of docosahexaenoic acid (DHA), the major long chain polyunsaturated fatty acids (PUFAs) found in fish oil, added to cell culture media can cause tumour cell death but not kill cultured normal cells (de Vries and Van Noorden, 1992). Other reported benefits of omega-3 PUFA dietary supplements given prior to or during cancer therapy include: reversing tumour cell drug resistance (Das et al, 1998), reducing the gastrointestinal, haematological or cardiac side effects of various chemotherapeutic treatments (Hardman et al, 1999a;Germain et al, 1999;Shao et al, 1997), decreasing cancer cachexia (Karmali, 1996;Tisdale, 1993;Barber et al, 1999), and protection from alopecia (Takahata et al, 1999). Thus supplementing the diet with omega-3 fatty acids may be beneficial during cancer chemotherapy.…”

NF-κB pathway inhibitors preferentially inhibit breast cancer stem-like cells

“…The in vivo experiments were performed in accordance with the guidelines of our institute. For mice in MCF7 xenograft study, the mice were given injections of β-estradiol (Sigma) dissolved in pure sesame oil (0.1 mg per 0.05 ml sesame oil per mouse, subcutaneously) 1 day before the injection of MCF7 cells and then at weekly intervals [30,31]. Mice were inoculated subcutaneously with 2 × 10 7 MCF7 cells.…”