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

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 sc...

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Main Authors: Mat Pauzi, Ahmad Zaim, Yeap, Swee Keong, Abu, Nadiah, Lim, Kian Lam, Omar, Abdul Rahman, Abd. Aziz, Suraini, Leow, Adam Thean Chor, Subramani, Tamilselvan, Tan, Soon Guan, Mohammed Alitheen, Noorjahan Banu
Format: Article
Language:English
Published: BioMed Central 2016
Online Access:http://psasir.upm.edu.my/id/eprint/55309/1/Combination%20of%20cisplatin%20and%20bromelain.pdf
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spelling oai:psasir.upm.edu.my:55309 http://psasir.upm.edu.my/id/eprint/55309/ Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro Mat Pauzi, Ahmad Zaim Yeap, Swee Keong Abu, Nadiah Lim, Kian Lam Omar, Abdul Rahman Abd. Aziz, Suraini Leow, Adam Thean Chor Subramani, Tamilselvan Tan, Soon Guan Mohammed Alitheen, Noorjahan Banu 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. BioMed Central 2016 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/55309/1/Combination%20of%20cisplatin%20and%20bromelain.pdf 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 https://cmjournal.biomedcentral.com/articles/10.1186/s13020-016-0118-5 10.1186/s13020-016-0118-5
institution UPM IR
collection UPM IR
language English
description 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.
format Article
author Mat Pauzi, Ahmad Zaim
Yeap, Swee Keong
Abu, Nadiah
Lim, Kian Lam
Omar, Abdul Rahman
Abd. Aziz, Suraini
Leow, Adam Thean Chor
Subramani, Tamilselvan
Tan, Soon Guan
Mohammed Alitheen, Noorjahan Banu
spellingShingle Mat Pauzi, Ahmad Zaim
Yeap, Swee Keong
Abu, Nadiah
Lim, Kian Lam
Omar, Abdul Rahman
Abd. Aziz, Suraini
Leow, Adam Thean Chor
Subramani, Tamilselvan
Tan, Soon Guan
Mohammed Alitheen, Noorjahan Banu
Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro
author_facet Mat Pauzi, Ahmad Zaim
Yeap, Swee Keong
Abu, Nadiah
Lim, Kian Lam
Omar, Abdul Rahman
Abd. Aziz, Suraini
Leow, Adam Thean Chor
Subramani, Tamilselvan
Tan, Soon Guan
Mohammed Alitheen, Noorjahan Banu
author_sort Mat Pauzi, Ahmad Zaim
title Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro
title_short Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro
title_full Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro
title_fullStr Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro
title_full_unstemmed Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro
title_sort combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line mda-mb-231 in vitro
publisher BioMed Central
publishDate 2016
url http://psasir.upm.edu.my/id/eprint/55309/1/Combination%20of%20cisplatin%20and%20bromelain.pdf
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score 13.4562235

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