Bromelain-Induced Apoptosis in GI-101A Breast Cancer Cells

Dhandayuthapani, Sivanesan; Perez, Honey Diaz; Paroulek, Alexandra F; Panneerselvam, Chinnakkannu; Kandalam, Umadevi; Jaffe, Mark; Rathinavelu, Appu

doi:10.1089/jmf.2011.0145

Cited by 53 publications

(44 citation statements)

References 22 publications

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“…In contrast, the inhibitory effects of bromelain are dependent on its proteolytic activity, which allow it to remove certain cell surface molecules associated with cellular migration and adherence [27]. The proteolytic activity of bromelain has also been reported to promote apoptosis in a number of human cancer cells, particularly in breast cancer cells [18, 28]. …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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BackgroundBromelain, 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.MethodMDA-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.ResultsSingle-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).ConclusionBromelain in combination with cisplatin synergistically enhanced the induction of apoptosis in MDA-MB-231 cells.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2016

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“…Anticancer properties of bromelain or NAC, individually, have been evaluated in some in vitro and in vivo models before. Bromelain has shown cytotoxic and/or cytostatic effects on murine lung carcinoma, mammary adenocarcinoma, leukemia, lymphoma, sarcoma, melanoma and ascitic tumor cell lines [23][24][25][26], as well as on human cell lines derived from gastric and colon carcinoma [23,27,28], glioma [29], breast cancer [30][31][32], epidermoid carcinoma, melanoma [33] and malignant peritoneal mesothelioma [34]. Bromelain was also found to induce differentiation of leukemia cell lines in vitro [35] and to exert chemopreventive effects on skin [36][37][38] and colon [28] tumorigenesis in vivo.…”

Section: Discussionmentioning

confidence: 99%

Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro : significance of combination therapy

Amini

Masoumi-Moghaddam

Ehteda

et al. 2014

J Exp Clin Cancer Res

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BackgroundBromelain and N-acetylcysteine are two natural, sulfhydryl-containing compounds with good safety profiles which have been investigated for their benefits and application in health and disease for more than fifty years. As such, the potential values of these agents in cancer therapy have been variably reported in the literature. In the present study, the efficacy of bromelain and N-acetylcysteine in single agent and combination treatment of human gastrointestinal carcinoma cells was evaluated in vitro and the underlying mechanisms of effect were explored.MethodsThe growth-inhibitory effects of bromelain and N-acetylcysteine, on their own and in combination, on a panel of human gastrointestinal carcinoma cell lines, including MKN45, KATO-III, HT29-5F12, HT29-5M21 and LS174T, were assessed by sulforhodamine B assay. Moreover, the influence of the treatment on the expression of a range of proteins involved in the regulation of cell cycle and survival was investigated by Western blot. The presence of apoptosis was also examined by TUNEL assay.ResultsBromelain and N-acetylcysteine significantly inhibited cell proliferation, more potently in combination therapy. Drug-drug interaction in combination therapy was found to be predominantly synergistic or additive. Mechanistically, apoptotic bodies were detected in treated cells by TUNEL assay. Furthermore, Western blot analysis revealed diminution of cyclins A, B and D, the emergence of immunoreactive subunits of caspase-3, caspase-7, caspase-8 and cleaved PARP, withering or cleavage of procaspase-9, overexpression of cytochrome c, reduced expression of anti-apoptotic Bcl-2 and pro-survival phospho-Akt, the emergence of the autophagosomal marker LC3-II and deregulation of other autophagy-related proteins, including Atg3, Atg5, Atg7, Atg12 and Beclin 1. These results were more prominent in combination therapy.ConclusionWe report for the first time to our knowledge the growth-inhibitory and cytotoxic effects of bromelain and N-acetylcysteine, in particular in combination, on a panel of gastrointestinal cancer cell lines with different phenotypes and characteristics. These effects apparently resulted from cell cycle arrest, apoptosis and autophagy. Towards the development of novel strategies for the enhancement of microscopic cytoreduction, our results lay the basis for further evaluation of this formulation in locoregional approaches to peritoneal surface malignancies and carcinomatosis.

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“…Dhandayuthapani et al confirmed the dose‐dependent cytotoxic effects of bromelain in the GI‐101A breast cancer cell line. Bromelain was found to increase the level of caspase‐cleaved cytokeratin (CK18), one of the markers indicating cell death via apoptosis.…”

Section: Applicationsmentioning

confidence: 91%

Stability, purification, and applications of bromelain: A review

Novaes

Jozala

Lopes

et al. 2015

Biotechnol Progress

126

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Bromelain is a cysteine protease found in pineapple tissue. Because of its anti-inflammatory and anti-cancer activities, as well as its ability to induce apoptotic cell death, bromelain has proved useful in several therapeutic areas. The market for this protease is growing, and several studies exploring various properties of this molecule have been reported. This review aims to compile this data, and summarize the main findings on bromelain in the literature to date. The physicochemical properties and stability of bromelain under different conditions are discussed. Several studies on the purification of bromelain from crude extracts using a wide range of techniques such as liquid-liquid extractions by aqueous two-phase system, ultrafiltration, precipitation, and chromatography, have been reported. Finally, the various applications of bromelain are presented. This review therefore covers the main properties of bromelain, aiming to provide an up-to-date compilation of the data reported on this enzyme.

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Bromelain-Induced Apoptosis in GI-101A Breast Cancer Cells

Cited by 53 publications

References 22 publications

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

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

Bromelain and N-acetylcysteine inhibit proliferation and survival of gastrointestinal cancer cells in vitro : significance of combination therapy

Stability, purification, and applications of bromelain: A review

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