title: Depletion of mucin in mucin-producing human gastrointestinal carcinoma: Results from in vitro and in vivo studies with bromelain and N-acetylcysteine.
abstract: Aberrant expression of membrane-associated and secreted mucins, as evident in epithelial tumors, is known to facilitate tumor growth, progression and metastasis, and to provide protection against adverse growth conditions, chemotherapy and immune surveillance. Emerging evidence provides support for the oncogenic role of MUC1 in gastrointestinal carcinomas and relates its expression to an invasive phenotype. Similarly, mucinous differentiation of gastrointestinal tumors, in particular increased or de novo expression of MUC2 and/or MUC5AC, is widely believed to imply an adverse clinicopathological feature. Through formation of viscous gels, too, MUC2 and MUC5AC significantly contribute to the biology and pathogenesis of mucin-secreting gastrointestinal tumors. Here, we investigated the mucin-depleting effects of bromelain (BR) and N-acetylcysteine (NAC), in nine different regimens as single or combination therapy, in in vitro (MKN45, KATOIII and LS174T cell lines) and in vivo (female nude mice bearing intraperitoneal MKN45 and LS174T) settings. The inhibitory effects of the treatment on cancer cell growth and proliferation were also evaluated in vivo. Our results suggest that a combination of BR and NAC with dual effects on growth and mucin products of mucin-expressing tumor cells is a promising candidate towards the development of novel approaches to gastrointestinal malignancies with the involvement of mucin pathology. This capability supports the use of this combination formulation in locoregional approaches for reducing the adverse effects of the aberrantly secreted gel-forming mucins, as in pseudomyxoma peritonei and similar pathologies with ectopic production of mucin.
authors.affiliation: Department of Surgery, St George Hospital, The University of New South Wales, Kogarah, Sydney NSW 2217, Australia.
authors.forename: Afshin
authors.initials: A
authors.lastname: Amini
authors.affiliation: Department of Surgery, St George Hospital, The University of New South Wales, Kogarah, Sydney NSW 2217, Australia.
authors.forename: Samar
authors.initials: S
authors.lastname: Masoumi-Moghaddam
authors.affiliation: Department of Surgery, St George Hospital, The University of New South Wales, Kogarah, Sydney NSW 2217, Australia.
authors.forename: Anahid
authors.initials: A
authors.lastname: Ehteda
authors.affiliation: Cancer Care Center, St George Hospital, The University of New South Wales, Kogarah, Sydney NSW 2217, Australia.
authors.forename: Winston
authors.initials: W
authors.lastname: Liauw
authors.affiliation: Department of Surgery, St George Hospital, The University of New South Wales, Kogarah, Sydney NSW 2217, Australia.
authors.forename: David L
authors.initials: DL
authors.lastname: Morris
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001963:Bromelains / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008819:Mice, Nude; D055271:Mucin 5AC / Q000037:antagonists & inhibitors; D055262:Mucin-2 / Q000037:antagonists & inhibitors; D009077:Mucins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D055262:Mucin-2; D009077:Mucins; D001963:Bromelains; D000111:Acetylcysteine
keywords: N-acetylcysteine; bromelain; gastrointestinal cancers; mucin; mucin-depleting effect