Abstract 1629: Dietary modification of colon and hepatic tumorigenesis

Abstract

Abstract Goal: The goal of this study was to determine if a multi-mineral natural product derived from the skeletal remains of the red marine algae, Lithothamnion calcareum, could inhibit gastro-intestinal tumor formation. Several dietary features of the western style diet are known to contribute to liver and colon tumorigenesis, but a role for a deficiency in essential minerals has not been explored. Methods: To address this question, C57BL/6 mice were maintained for 5, 12 and 18 months on either a low fat diet or a high fat “Western-style” diet with or without a mineral-rich product, as a dietary supplement. At the end of incubation period, animals were sacrificed and colon polyp formation was assessed by stereomicroscopy and confirmed histologically. Liver masses were also identified grossly and characterized histologically. Results: Liver: While all the livers appeared normal at 5 months, numerous liver masses were visible in the high fat diet mice sacrificed after 12 and 18 months. The majority of masses were in male mice (20 out of 100 males versus 3 out of 100 females, p=0.0002) and in male animals on high fat diet than on low fat diet (15 out of 50 versus 5 out of 50, p=0.0228).The multi-mineral supplement reduced the number of liver masses in male mice (4 of 50 mice in the mineral-supplemented diet groups compared to 16 of 50 mice without the supplement, p=0.0050). Histological evaluation revealed a total of 17 neoplastic lesions (9 adenomas and 8 hepatocellular carcinomas). Out of 8 hepatocellular carcinomas, 7 were found in unsupplemented diet groups and only one in mice on supplemented high fat diet. Colon: High fat diet induced colon polyps in two female mice at 5 months. Several polyps were detected at 12 and 18 months, most of these lesions were found in female mice (34 out of 100 females versus 11 out of 100 males, p=0.0002). Supplement reduced the incidence of polyps in the presence of high-fat from 18 of 50 female mice to 2 of 50 (p<0.0001). Colon polyps were detected in 15 of 50 mice in the low-fat unsupplemented diet group; not significantly different from the non-supplemented high fat group or supplemented low fat group but significantly higher than the high fat supplemented group (p=0.0009). This was in spite of the fact that the calcium level in the low fat diet was comparable to the level of calcium in the high fat supplemented diet. Histologically, there were 8 tumors identified as adenocarcinomas, 7 as adenomas, and 7 as foci of hyperplasia. Out of 8 adenocarcinomas, 7 were found in unsupplemented diet groups, one found in mice on supplemented low fat diet and zero in mineral-rich high fat diet group. Conclusion: These findings demonstrate that a multi-mineral natural product can protect mice on a high fat diet against adenomatous polyp formation in the colon and liver injury. These data suggest that a multi-mineral approach to colon polyp chemoprevention may be more effective than supplementation with calcium alone and the protective role for dietary minerals in liver cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1629. doi:1538-7445.AM2012-1629