Anti-Tumour and Chemosensitising Effect of a Combination of Bromelain + N-Acetyl Cysteine with Cisplatin or 5-Fu on Malignant Peritoneal Mesothelioma Cells

نویسندگان

  • Krishna Pillai
  • Javid Akhter
  • Anahid Ehteda
  • Samina Badar
  • Terence C Chua
  • David L Morris
چکیده

Background: Malignant Peritoneal Mesothelioma (MPM) is a rare asbestos related peritoneal neoplasm. Survival is normally poor however, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy has increased survival in some patients. Hence, new therapies are needed. MUC1 is a glycosylation dependant protein associated with tumour invasiveness, metastasis and chemo resistance. Bromelain, a cysteine proteinase, hydrolyses glycosidic bonds, whilst N-Acetyl cysteine reduces disulphide bonds in glycoprotein. Hence, we investigated the anti-tumour effect of these agents in MUC 1 expressing MPM cell lines. Materials and Methods: The cell lines were treated to various concentrations of bromelain, NAC and combinations of NAC + bromelain, NAC + bromelain + cisplatin or 5-FU. Their cell viabilities were assessed at 48 hours with sulfhordamine B assay. Finally, with western blotting, the effect of NAC and the combination of NAC + bromelain on cellular survival proteins were investigated. Results: Combination of NAC (10 mM) with bromelain (75 ug/ml) showed 97% and 88% cell proliferation inhibition in YOU and PET cells, respectively. In triple combination, the addition of cisplatin to only 5.0 mM NAC and bromelain increased cytotoxicity in YOU cells but absent at 10.0 mM NAC concentration. However, in PET cells, triple combinations with cisplatin had no effect. The addition of 5-FU in triple combinations showed an increase in cytotoxicity with 5.0 mM NAC and bromelain in YOU cells. No increase in cytotoxicity was seen with addition of 10 mM NAC. In PET cells, the addition 5-FU to 5.0 mM NAC + 50 ug/ml bromelain, enhanced cytotoxicity significantly but was absent at all other combinations. Conclusion: The combination of bromelain and NAC may be developed as antitumour agents for treating MPM, with a possible role in combined therapy with current chemotherapeutic agents. *Corresponding author: David L Morris, Department of Surgery, University of New South Wales, St George Hospital, Kogarah, Australia, Tel: +612 – 9112070; Fax: +612 – 91133997; E-mail: [email protected] Received April 26, 2013; Accepted June 27, 2013; Published June 29, 2013 Citation: Pillai K, Akhter J, Ehteda A, Badar S, Chua TC, et al. (2013) Anti-Tumour and Chemosensitising Effect of a Combination of Bromelain + N-Acetyl Cysteine with Cisplatin or 5-Fu on Malignant Peritoneal Mesothelioma Cells. J Glycobiol S1: 005. doi:10.4172/2168-958X.S1-005 Copyright: © 2013 Pillai K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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تاریخ انتشار 2013