Comparative study of antitumor effects of bromelain and papain in human cholangiocarcinoma cell lines

  • Authors:
    • Alena Müller
    • Samarpita Barat
    • Xi Chen
    • Khac Cuong Bui
    • Przemyslaw Bozko
    • Nisar P. Malek
    • Ruben R. Plentz
  • View Affiliations

  • Published online on: March 1, 2016     https://doi.org/10.3892/ijo.2016.3411
  • Pages: 2025-2034
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Cholangiocarcinoma (CC) worldwide is the most common biliary malignancy with poor prognostic value and new systemic treatments are desirable. Plant extracts like bromelain and papain, which are cysteine proteases from the fruit pineapple and papaya, are known to have antitumor activities. Therefore, in this study for the first time we investigated the anticancer effect of bromelain and papain in intra- and extrahepatic human CC cell lines. The effect of bromelain and papain on human CC cell growth, migration, invasion and epithelial plasticity was analyzed using cell proliferation, wound healing, invasion and apoptosis assay, as well as western blotting. Bromelain and papain lead to a decrease in the proliferation, invasion and migration of CC cells. Both plant extracts inhibited NFκB/AMPK signalling as well as their downstream signalling proteins such as p-AKT, p-ERK, p-Stat3. Additionally, MMP9 and other epithelial-mesenchymal-transition markers were partially found to be downregulated. Apoptosis was induced after bromelain and papain treatment. Interestingly, bromelain showed an overall more effective inhibition of CC as compared to papain. siRNA mediated silencing of NFκB on CC cells indicated that bromelain and papain have cytotoxic effects on human CC cell lines and bromelain and partially papain in comparison impair tumor growth by NFκB/AMPK signalling. Especially bromelain can evolve as promising, potential therapeutic option that might open new insights for the treatment of human CC.

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May 2016
Volume 48 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Müller, A., Barat, S., Chen, X., Bui, K.C., Bozko, P., Malek, N.P., & Plentz, R.R. (2016). Comparative study of antitumor effects of bromelain and papain in human cholangiocarcinoma cell lines. International Journal of Oncology, 48, 2025-2034. https://doi.org/10.3892/ijo.2016.3411
MLA
Müller, A., Barat, S., Chen, X., Bui, K. C., Bozko, P., Malek, N. P., Plentz, R. R."Comparative study of antitumor effects of bromelain and papain in human cholangiocarcinoma cell lines". International Journal of Oncology 48.5 (2016): 2025-2034.
Chicago
Müller, A., Barat, S., Chen, X., Bui, K. C., Bozko, P., Malek, N. P., Plentz, R. R."Comparative study of antitumor effects of bromelain and papain in human cholangiocarcinoma cell lines". International Journal of Oncology 48, no. 5 (2016): 2025-2034. https://doi.org/10.3892/ijo.2016.3411