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 apop-tosis 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.
References
1. DeSantis CE, Lin LC, Mariotto AB, Siegel RL, Stein KD, Kramer JL, et al. Cancer treatment and survivorship statistics, 2014. CA Cancer J Clin. 2014;64(4):252-71.
2. Raeisi E, Aghamiri SM, Bandi A, Rahmatpour N, Firoozabadi SM, Kafi-Abad SA, et al. The antitumor efficiency of combined electrochemotherapy and single dose irradiation on a breast cancer tumor model. Radiol Oncol. 2012;46(3):226-32.
3. Pérez-Herrero E, Fernández-Medarde A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm. 2015;93:52-79.
4. Ghosh S. Cisplatin: The first metal based anticancer drug. Bioorg Chem. 2019;88:102925.
5. Damia G, Broggini M. Platinum resistance in ovarian cancer: Role of DNA repair. Cancers (Basel). 2019;11(1):119.
6. Maehara Y, Oki E, Saeki H, Tokunaga E, Kitao H, Iimori M, et al. Evolving 5-fluorouracil therapy to achieve enhanced efficacy-past and current efforts of researchers. Gan To Kagaku Ryoho. 2016;43(7):845-54.
7. Sun W, Sanderson P, Zheng W. Drug combination therapy increases successful drug repositioning. Drug Discov Today. 2016;21(7): 1189-95.
8. Rathnavelu V, Alitheen N, Sohila S, Kanagesan S, Ramesh R. Potential role of bromelain in clinical and therapeutic applications. Biomed Rep. 2016;5(3):283-8.
9. Satari A, Amini AS, Raeisi E, Lemoigne Y, Hiedarian E. Synergetic impact of combined 5-fluorouracil and rutin on apoptosis in pc3 cancer cells through the modulation of p53 gene expression. Adv Pharm Bull. 2019;9(3):462-9.
10. Pauzi AZ, Yeap S, Abu N, Lim KL, Omar AR, Aziz SA, et al. Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro. Chin Med. 2016;11:46.
11. Raeisi F, Shahbazi-Gahrouei D, Raeisi E, Heidarian E. Evaluation of the radiosensitizing potency of bromelain for radiation therapy of 4t1 breast cancer cells. J Med Signals Sens. 2019;9(1):68-74.
12. Amini A, Masoumi-Moghaddam S, Ehteda A, Morris DL. Bromelain and n-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro: Significance of combination therapy. J Exp Clin Cancer Res. 2014;33(1):92.
13. Amini A, Masoumi-Moghaddam S, Ehteda A, Liauw W, Morris DL. Potentiation of chemotherapeutics by bromelain and n-acetylcysteine: Sequential and combination therapy of gastrointestinal cancer cells. Am J Cancer Res. 2016;6(2):350-69.
14. Müller A, Barat S, Chen X, Bui KC, Bozko P, Malek NP, et al. Comparative study of antitumor effects of bromelain and papain in human cholangiocarcinoma cell lines. Int J Oncol. 2016;48(5):2025-34.
15. Pillai K, Ehteda A, Akhter J, Chua TC, Morris DL. Anticancer effect of bromelain with and without cisplatin or 5-fu on malignant peritoneal mesothelioma cells. Anticancer Drugs. 2014;25(2):150-60.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 Unported License.
Copyright (c) 2020 Authors