Aims: Towards the development of novel supplementary strategies for locoregional treatment of peritoneal surface malignancies, we investigated in the present study growth-inhibitory and mucin-depleting properties of bromelain (BR) and N-acetylcysteine (NAC) in combination therapy of gastrointestinal cancer cells and in vivo models of peritoneal dissemination.
Materials and methods: Cytotoxic effects of different concentrations of BR/NAC on MKN45 gastric and LS174T colon cancer cell lines were determined by sulforhodamine B (SRB) assay. The expression of MUC2 and MUC5AC mucins before and after 48h treatment was evaluated by immunocytochemistry. Tumor growth-inhibitory effects of intraperitoneal BR/NAC on MKN45- and LS174T-induced models of peritoneal carcinomatosis (PC) and pseudomyxoma peritonei (PMP)-like syndrome were explored in vivo and the expression of MUC2 and MUC5AC in tumor samples was evaluated by immunohistochemistry.
Results: BR and NAC, more potently in combination, inhibited cancer cell proliferation and mucin expression in vitro. Intraperitoneal administration of BR/NAC significantly suppressed tumor growth and reduced intratumoral mucin expression.
Discussion and conclusion: BR and NAC are two natural agents with good safety profiles. At concentrations within the safe range reported in the literature, BR and NAC indicated growth-inhibitory and mucin-depleting effects on gastrointestinal cancer cells and their animal models of PC and PMP. This novel formulation with dual activity on malignant cells and their mucin product could be of potential value in locoregional approaches to peritoneal surface malignancies.