Malignant peritoneal
mesothelioma (MPM) is a rare
neoplasm of the peritoneum, causally related to
asbestos exposure. Nonspecific symptoms with a late diagnosis results in poor survival (<1 year). Treatment with
cytoreductive surgery and
hyperthermic intraperitoneal chemotherapy has improved survival in some patients (median 3-5 years). Hence, new
therapies are urgently needed. MUC1 is a glycosylation-dependent
protein that confers tumours with invasiveness,
metastasis and chemoresistance.
Bromelain (
cysteine proteinase) hydrolyses glycosidic bonds. Therefore, we investigated the antitumour effect of
bromelain on MUC1-expressing MPM cell lines. MUC1 expressions in cells were assessed using immunofluorescent probes with cells grown on cover slips and western blot analysis on cell lysates. The cell lines were treated with various concentrations of
bromelain and after 4 and 72 h, their viability was assessed using standard sulforhodamine assays. The cells were also treated with combinations of
bromelain and cytotoxic drugs (
cisplatin or 5-FU) and their viability was assessed at 72 h. Finally, with western blotting, the effects of
bromelain on cellular survival
proteins were investigated. PET cells expressed more MUC1 compared with YOU cells. The cell viability of both PET and YOU cells was adversely affected by
bromelain, with PET cells being slightly resistant. The addition of
bromelain increased the cytotoxicity of
cisplatin significantly in both cell lines. However,
5-FU with
bromelain did not show any significant increase in cytotoxicity.
Bromelain-induced cell death is by apoptosis and autophagy.
Bromelain has the potential of being developed as a therapeutic agent in MPM.