Bromelain-based chemo-herbal combination effect on human cancer cells: in-vitro study on AGS and MCF7 proliferation and apoptosis

Abstract

Abstract Aim. Chemo-herbal combinations promise new clinical anticancer therapeutic modalities. The current study investigated and compared the in vitro effects of a bromelain-based chemo-herbal combination to/with cisplatin or 5-FU, with regard to the proliferation and apoptosis of human gastric AGS and breast MCF7 cell lines. Material and methods. AGS and MCF7 cells were either treated with different concentrations of bromelain, cisplatin or 5-FU; or with bromelain-cisplatin and bromelain-5-FU combinations for 48h. Cell proliferative inhibition and inductive apoptosis were appraised using MTT assay and flowcytometry, respectively. Kruskal-Wallis and Dunn’s tests were used to analyze differences in cell groups’ means. Results. AGS proliferation was adversely affected by single treatments of bromelain and cisplatin (p <0.003) or 5-FU (p <0.05). The anti-proliferative impact of single treatments was more pronounced on MCF7 cells. The bromelain-cisplatin combinations displayed synergistic effect on MCF7 cells (CIs ≤1), while being additive or antagonistic with cisplatin IC30 and IC40 to AGS cell proliferation, respectively. In addition, bromelian-5-FU combinations showed synergistic effect on AGS cells, while antagonistic to MCF7 cells. In terms of cell apoptosis induction, bromelain (IC30)-cisplatin (IC20) displayed additive effect on MCF7, compared to cisplatin single treatment (p <0.04), while bromelain (IC40)-5-FU (IC10) and bromelain (IC30)-5-FU (IC20) afforded additive apoptotic effects on AGS (p <0.04) and MCF7 (p <0.05), respectively, in comparison to 5-FU single treatment. Conclusion. A bromelain-based combination using cisplatin showed concordant effects on cell proliferation impediment and apoptotic induction on MCF7, while the same results were noticed with a bromelain-5-FU combination to AGS cells. The bromelain-based chemo-herbal pathways should further be investigated in the frame of multi-chemotherapeutic drugs researches.