Simple SummaryCancer is one of the major current public health threats worldwide that needs new forms of treatment. The seeds ofEuterpe oleraceafruit, popularly known as açaí, are part of the fruit that are rejected during its processing for consumption, although the seeds have several compounds with pharmacological potential. This study aimed to evaluate the effect of açai seed extract against cancer cells in vitro and in vivo in animals with an Ehrlich tumor, an inflammatory mammary type of cancer. The açai seed extract displayed a rich chemical composition with a high content of catechin/epicatechin. Prostate cancer cell lines were killed by açai seed extract treatment in vitro. Animals with an Ehrlich tumor treated with açai seed extract showed a decrease in tumor size and an enhancement of the immunological response against the tumor. All these results point to a promising antitumor effect of açai seed extract that should be further clarified.AbstractEuterpe oleracea(açaí) fruit has approximately 15% pulp, which is partly edible and commercialized, and 85% seeds. Although açaí seeds are rich in catechins—polyphenolic compounds with antioxidant, anti-inflammatory, and antitumor effects—almost 935,000 tons/year of seeds are discarded as industrial waste. This work evaluated the antitumor properties ofE. oleraceain vitro and in vivo in a solid Ehrlich tumor in mice. The seed extract presented 86.26 ± 0.189 mg of catechin/g of extract. The palm and pulp extracts did not exhibit in vitro antitumor activity, while the fruit and seed extracts showed cytotoxic effects on the LNCaP prostate cancer cell line, inducing mitochondrial and nuclear alterations. Oral treatments were performed daily at 100, 200, and 400 mg/kg ofE. oleraceaseed extract. The tumor development and histology were evaluated, along with immunological and toxicological parameters. Treatment at 400 mg/kg reduced the tumor size, nuclear pleomorphism, and mitosis figures, increasing tumor necrosis. Treated groups showed cellularity of lymphoid organs comparable to the untreated group, suggesting less infiltration in the lymph node and spleen and preservation of the bone marrow. The highest doses reduced IL-6 and induced IFN-γ, suggesting antitumor and immunomodulatory effects. Thus, açaí seeds can be an important source of compounds with antitumor and immunoprotective properties.