Athanara Alves de Sousa1*、Taline Alves Nobre2、Jorddam Almondes Martins1、Kennyana Luz Miranda2、Ana Rafaela Silva Pereira2、Marlene Gomes de Farias2、Ingredy Lopes dos Santos3、Felipe Pantoja Mesquita4、Raquel Carvalho Montenegro4、Jose Roberto Ferreira Junior5、Nicole Debia1、Felipe卡瓦尔坎蒂·卡内罗·达·席尔瓦2,6、胡安·卡洛斯·拉莫斯·贡萨尔维斯7、安德森·诺盖拉·门德斯8、保罗·米歇尔·皮涅罗·费雷拉8、若昂·马塞洛·德卡斯特罗·索萨1
Use of dietary components as antineoplastic agents has been highlighted due to their high biological activity against tumor cells, chemo preventive effects and low toxicity. The present study evaluated antitumor effects and chemo protective potential of Bromelain (BL) alone and in combination with Doxorubicin (DOX) using in vitro tests: Alamar blue in the lines: AGP01, SKMEL103 and CAL27; MTT assay (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide), fluorescent labelling in murine Sarcoma 180 (S180) and comet assay in human lymphocytes. Cytotoxic effects of BL were noted with IC50 (μg/mL) of 124.80 (AGP01), 91.81 (SKMEL103), 95.75 (CAL27) and 25.27 (S180). When incubated in a BL+DOX combination, they demonstrated combination indices ranging from synergistic to antagonistic. In the cell death mechanism at S180, an increase in the number of cells undergoing early apoptosis was observed after incubation with BL (100 μg/mL). In genotoxicity assays, isolated BL was not genotoxic in human lymphocytes, unlike DOX. When combined (BL+DOX), BL modulated the DNA damage caused by the antineoplastic agent when compared to DOX alone, with Inhibition Degree (ID) values of 55.91% and Fractional Difference (FD) of 33.65%, presenting chemo protective potential. Thus, isolated BL exhibited ant proliferative effects on tumour lineages and was not genotoxic to human blood cells, with positive prospects for use in combination with DOX chemotherapy.