Abstract LB-007: Synergistic inhibition of human gastric and colorectal cancers by Bromelain and N-acetylcysteine: An in vivo study

Abstract

Abstract Mucin is well understood to be an adverse prognostic factor in some cancers. We previously reported that a combination of Bromelain (BR) and N-acetylcysteine (NAC) were synergistic in dissolving pseudomyxoma peritonei mucin, had direct in vitro cytotoxic effects on some gastrointestinal cancer cells and sensitized them to some chemotherapy agents. In the present study, we aimed to evaluate the growth-inhibitory effect of BR and NAC as single agent or combination therapy in nude mice models of gastrointestinal cancer. Nude mice received 2 million and 1 million cells of MKN45 (gastric) and LS174T (colorectal) by intraperitoneal injection. At day 14 and 7 post inoculation for MKN45 and LS174T cells, respectively, animals were intraperitoneally administrated BR (3, 6 mg/kg), NAC (300, 500 mg/kg) or their combination every other day over 12 days for MKN45 and 17 days for LS174T models. At the end of the study, the animals were euthanized, the number of peritoneal nodules and their weight were collected, and the peritoneal tumors were subjected to immunohistochemistry for evaluation of MUC2. No toxicity was observed during the experiment. At necropsy, highly significant reductions in the number of tumor nodules and tumor burden were observed, in particular in the combination group, where almost complete inhibition in LS174T group was found. There was more than 95% and 70% decreases in tumor burden and tumor nodules, respectively, in LS174T group after combination treatment. For MKN45 model, the reductions in tumor burden and tumor nodules in combination groups were more than 60% and 70%, respectively. Performing immunohistochemistry on tumor samples, MUC2 staining of the LS174T xenografts showed a greater than 60% reduction of cytoplasmic staining. To the best of our knowledge, this is the first report of the in vivo use of this combination with synergistic inhibition of human gastric and colorectal cancers. The combination of BR and NAC in mucin secreting gastrointestinal tumors is interesting and could be of potential value in peritoneal cancer. Citation Format: Afshin Amini, Samar Masoumi-Moghaddam, Anahid Ehteda, Winston Liauw, Javed Akhter, Krishna Pilai, David L. Morris. Synergistic inhibition of human gastric and colorectal cancers by Bromelain and N-acetylcysteine: An in vivo study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-007. doi:10.1158/1538-7445.AM2015-LB-007