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.