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

Overview of attention for article published in Chinese Medicine, November 2016
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Combination of cisplatin and bromelain exerts synergistic cytotoxic effects against breast cancer cell line MDA-MB-231 in vitro
Published in
Chinese Medicine, November 2016
DOI 10.1186/s13020-016-0118-5
Pubmed ID

Ahmad Zaim Mat Pauzi, Swee Keong Yeap, Nadiah Abu, Kian Lam Lim, Abdul Rahman Omar, Suraini Abdul Aziz, Adam Leow Thean Chow, Tamilselvan Subramani, Soon Guan Tan, Noorjahan Banu Alitheen


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. 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. 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). Bromelain in combination with cisplatin synergistically enhanced the induction of apoptosis in MDA-MB-231 cells.

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Mendeley readers

The data shown below were compiled from readership statistics for 50 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 50 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 10 20%
Researcher 6 12%
Student > Ph. D. Student 6 12%
Student > Bachelor 4 8%
Other 4 8%
Other 10 20%
Unknown 10 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 17 34%
Agricultural and Biological Sciences 6 12%
Pharmacology, Toxicology and Pharmaceutical Science 3 6%
Medicine and Dentistry 3 6%
Chemistry 3 6%
Other 4 8%
Unknown 14 28%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 December 2016.
All research outputs
of 9,727,557 outputs
Outputs from Chinese Medicine
of 257 outputs
Outputs of similar age
of 223,045 outputs
Outputs of similar age from Chinese Medicine
of 5 outputs
Altmetric has tracked 9,727,557 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 257 research outputs from this source. They receive a mean Attention Score of 4.7. This one is in the 32nd percentile – i.e., 32% of its peers scored the same or lower than it.
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We're also able to compare this research output to 5 others from the same source and published within six weeks on either side of this one.