Antitumoral and chemoprotective evaluation of isolated Bromelain and in combination with Doxorubicin

Abstract

Abstract The use of dietary components as new antineoplastic agents has been highlighted due to their high biological activity against tumor cells, chemopreventive effects and relatively low toxicity. The present study evaluated the antitumor effects and chemoprotective potential of the bromelain enzyme complex (BL) alone and in combination with the chemotherapy drug doxorubicin (DOX) using the following in vitro tests: cell viability by Alamar blue in cells: AGP01, SKMEL-103 and CAL-27 lines; MTT assay and fluorescent labeling in murine sarcoma 180 (S-180); and the comet assay in human lymphocytes. The results showed cytotoxic effects of BL with IC50 (µg/mL) of 124.80 (AGP-01), 91.81 (SKMEL-103), 95.75 (CAL-27) and 25.27 (S-180). When incubated with the BL + DOX combination, the IC50s were (in µg/mL) 26.29 (AGP-01), 29.04 (SKMEL-103), 2.68 (CAL-27) and 6.11 (S -180), demonstrating combination indices ranging from synergistic to antagonistic. When evaluating the mechanism of cell death in S-180, 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, which showed this activity. When combined (BL + DOX), BL modulated the DNA damage caused by the antineoplastic agent when compared to DOX alone, with ID values ​​of 55.91% and FD of 33.65%, showing chemoprotective potential in this case. In conclusion, isolated BL exhibited antiproliferative effects on tumor cell lines and was not genotoxic to human blood cells, with positive prospects for its use in combination with DOX chemotherapy.