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Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro


Mat Pauzi, Ahmad Zaim and Yeap, Swee Keong and Abu, Nadiah and Lim, Kian Lam and Omar, Abdul Rahman and Abd. Aziz, Suraini and Leow, Adam Thean Chor and Subramani, Tamilselvan and Tan, Soon Guan and Mohammed Alitheen, Noorjahan Banu (2016) Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro. Chinese Medicine, 11. art. no. 46. pp. 1-11. ISSN 1749-8546


Background: Bromelain, which is a cysteine endopeptidase commonly found in pineapple stems, has been investigated as a potential anti-cancer agent for the treatment of breast cancer. However, information pertaining to the effects of combining bromelain with existing chemotherapeutic drugs remains scarce. This study aimed to investigate the possible synergistic cytotoxic effects of using bromelain in combination with cisplatin on MDA-MB-231 human breast cancer cells. Method: MDA-MB-231 cells were treated with different concentrations (0.24–9.5 µM) of bromelain or cisplatin alone, as well as four different combinations of these two agents to assess their individual and combination effects after 24 and 48 h. Cell viability was analyzed using an MTT assay. The induction of apoptosis was assessed using cell cycle analysis and an Annexin V-FITC assay. The role of the mitochondrial membrane potential in the apoptotic process was assessed using a JC-1 staining assay. Apoptotic protein levels were assessed by western blot analysis and proteome profiling using an antibody array kit. Results: Single-agent treatment with cisplatin or bromelain led to dose- and time-dependent decreases in the viability of the MDA-MB-231 cells at 24 and 48 h. Furthermore, most of the combinations evaluated in this study displayed synergistic effects against MDA-MB-231 cells at 48 h, with combination 1 (bromelain 2 µM + cisplatin 1.5 µM) exhibiting the greatest synergistic effect (P = 0.000). The results of subsequent assays indicated that combination 1 treatment induced apoptosis via mitochondria-mediated pathway. Combination 1 also resulted in significant decreases in the levels of several apoptotic proteins such as Bcl-x and HSP70, compared with bromelain (P = 0.002 and 0.000, respectively) or cisplatin (P = 0.000 and 0.001, respectively) single treatment. Notably, MDA-MB-231 cells treated with combination 1 showed increased levels of the pro-apoptotic proteins Bax compared with those treated with bromelain (P = 0.000) or cisplatin single treatment (P = 0.043). Conclusion: Bromelain in combination with cisplatin synergistically enhanced the induction of apoptosis in MDA-MB-231 cells.

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Additional Metadata

Item Type: Article
Divisions: Faculty of Biotechnology and Biomolecular Sciences
Institute of Bioscience
DOI Number: https://doi.org/10.1186/s13020-016-0118-5
Publisher: BioMed Central
Keywords: Breast cancer; Bromelain; MDA-MB-231 cells; Pineapple stems
Depositing User: Mohd Hafiz Che Mahasan
Date Deposited: 07 Nov 2017 02:14
Last Modified: 20 Mar 2018 02:53
Altmetrics: http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1186/s13020-016-0118-5
URI: http://psasir.upm.edu.my/id/eprint/55309
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