Polysaccharides from green sweet pepper increase the antineoplastic effect of methotrexate on mammary tumor cells

This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg^-1, p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg^-1 CAP (p.o.) + 1 mg kg^-1 MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg^-1, i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity.