Inhibition of chronic ulcerative colitis associated adenocarcinoma development in mice by inositol compounds

Jie Liao, Darren Seril, Allison L. Yang, Gary G. Lu, Guang Yu Yang

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Chronic inflammation is a well recognized risk factor for cancer and patients with long-standing ulcerative colitis (UC) are at an increased risk for colorectal carcinoma development. In order to prevent UC associated carcinogenesis, we tested the effects of inositol compounds (including inositol and hexaphosphate inositol) on UC-associated carcinogenesis in our novel mouse model. Female C57BL/6 mice were subjected to long-term, cyclic dextran sulfate sodium (DSS) treatment and fed a 2-fold iron-enriched diet. The inositol compounds were administered via the drinking fluid. In the DSS-plus-2-fold iron positive control group, colorectal adenocarcinoma incidence was 70.6% (24/34 mice) after 15 cycles of DSS treatment (1 DSS cycle = 7 day DSS treatment period followed by a 10 day recovery period). Tumor multiplicity was 1.26 ± 1.05 and tumor volume was 21.4 ± 5.2 mm 3. Adding 1% inositol, tumor incidence was statistically significantly reduced (42%, 9 of 21 mice with tumors), as was tumor multiplicity (0.5 ± 0.7) and tumor volume (4.2 ± 1.9 mm 3). Administration of hexaphosphate inositol noticeably reduced tumor incidence (50%, 12 mice with tumors out of 24 total), tumor multiplicity (0.8 ± 0.9) and tumor volume (12.3 ± 4.1 mm 3); however, the results were not statistically significant (P > 0.05). Further mechanistic studies showed that the inhibition of UC-associated carcinogenesis by inositol compounds might relate to their function on the modulation of macrophage mediated inflammation, nitro-oxidative stress and cell proliferation in UC-associated carcinogenesis. This study indicates that inositol compounds may have the potential to serve as preventive agents for chronic inflammation-carcinogenesis.

Original languageEnglish (US)
Pages (from-to)446-454
Number of pages9
JournalCarcinogenesis
Volume28
Issue number2
DOIs
StatePublished - Feb 1 2007

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Inositol
Ulcerative Colitis
Adenocarcinoma
Dextran Sulfate
Carcinogenesis
Neoplasms
Tumor Burden
Phytic Acid
Inflammation
Incidence
Iron
Inbred C57BL Mouse
Drinking
Colorectal Neoplasms
Oxidative Stress
Therapeutics
Macrophages
Cell Proliferation
Diet
Control Groups

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Liao, Jie ; Seril, Darren ; Yang, Allison L. ; Lu, Gary G. ; Yang, Guang Yu. / Inhibition of chronic ulcerative colitis associated adenocarcinoma development in mice by inositol compounds. In: Carcinogenesis. 2007 ; Vol. 28, No. 2. pp. 446-454.
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abstract = "Chronic inflammation is a well recognized risk factor for cancer and patients with long-standing ulcerative colitis (UC) are at an increased risk for colorectal carcinoma development. In order to prevent UC associated carcinogenesis, we tested the effects of inositol compounds (including inositol and hexaphosphate inositol) on UC-associated carcinogenesis in our novel mouse model. Female C57BL/6 mice were subjected to long-term, cyclic dextran sulfate sodium (DSS) treatment and fed a 2-fold iron-enriched diet. The inositol compounds were administered via the drinking fluid. In the DSS-plus-2-fold iron positive control group, colorectal adenocarcinoma incidence was 70.6{\%} (24/34 mice) after 15 cycles of DSS treatment (1 DSS cycle = 7 day DSS treatment period followed by a 10 day recovery period). Tumor multiplicity was 1.26 ± 1.05 and tumor volume was 21.4 ± 5.2 mm 3. Adding 1{\%} inositol, tumor incidence was statistically significantly reduced (42{\%}, 9 of 21 mice with tumors), as was tumor multiplicity (0.5 ± 0.7) and tumor volume (4.2 ± 1.9 mm 3). Administration of hexaphosphate inositol noticeably reduced tumor incidence (50{\%}, 12 mice with tumors out of 24 total), tumor multiplicity (0.8 ± 0.9) and tumor volume (12.3 ± 4.1 mm 3); however, the results were not statistically significant (P > 0.05). Further mechanistic studies showed that the inhibition of UC-associated carcinogenesis by inositol compounds might relate to their function on the modulation of macrophage mediated inflammation, nitro-oxidative stress and cell proliferation in UC-associated carcinogenesis. This study indicates that inositol compounds may have the potential to serve as preventive agents for chronic inflammation-carcinogenesis.",
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Inhibition of chronic ulcerative colitis associated adenocarcinoma development in mice by inositol compounds. / Liao, Jie; Seril, Darren; Yang, Allison L.; Lu, Gary G.; Yang, Guang Yu.

In: Carcinogenesis, Vol. 28, No. 2, 01.02.2007, p. 446-454.

Research output: Contribution to journalArticle

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N2 - Chronic inflammation is a well recognized risk factor for cancer and patients with long-standing ulcerative colitis (UC) are at an increased risk for colorectal carcinoma development. In order to prevent UC associated carcinogenesis, we tested the effects of inositol compounds (including inositol and hexaphosphate inositol) on UC-associated carcinogenesis in our novel mouse model. Female C57BL/6 mice were subjected to long-term, cyclic dextran sulfate sodium (DSS) treatment and fed a 2-fold iron-enriched diet. The inositol compounds were administered via the drinking fluid. In the DSS-plus-2-fold iron positive control group, colorectal adenocarcinoma incidence was 70.6% (24/34 mice) after 15 cycles of DSS treatment (1 DSS cycle = 7 day DSS treatment period followed by a 10 day recovery period). Tumor multiplicity was 1.26 ± 1.05 and tumor volume was 21.4 ± 5.2 mm 3. Adding 1% inositol, tumor incidence was statistically significantly reduced (42%, 9 of 21 mice with tumors), as was tumor multiplicity (0.5 ± 0.7) and tumor volume (4.2 ± 1.9 mm 3). Administration of hexaphosphate inositol noticeably reduced tumor incidence (50%, 12 mice with tumors out of 24 total), tumor multiplicity (0.8 ± 0.9) and tumor volume (12.3 ± 4.1 mm 3); however, the results were not statistically significant (P > 0.05). Further mechanistic studies showed that the inhibition of UC-associated carcinogenesis by inositol compounds might relate to their function on the modulation of macrophage mediated inflammation, nitro-oxidative stress and cell proliferation in UC-associated carcinogenesis. This study indicates that inositol compounds may have the potential to serve as preventive agents for chronic inflammation-carcinogenesis.

AB - Chronic inflammation is a well recognized risk factor for cancer and patients with long-standing ulcerative colitis (UC) are at an increased risk for colorectal carcinoma development. In order to prevent UC associated carcinogenesis, we tested the effects of inositol compounds (including inositol and hexaphosphate inositol) on UC-associated carcinogenesis in our novel mouse model. Female C57BL/6 mice were subjected to long-term, cyclic dextran sulfate sodium (DSS) treatment and fed a 2-fold iron-enriched diet. The inositol compounds were administered via the drinking fluid. In the DSS-plus-2-fold iron positive control group, colorectal adenocarcinoma incidence was 70.6% (24/34 mice) after 15 cycles of DSS treatment (1 DSS cycle = 7 day DSS treatment period followed by a 10 day recovery period). Tumor multiplicity was 1.26 ± 1.05 and tumor volume was 21.4 ± 5.2 mm 3. Adding 1% inositol, tumor incidence was statistically significantly reduced (42%, 9 of 21 mice with tumors), as was tumor multiplicity (0.5 ± 0.7) and tumor volume (4.2 ± 1.9 mm 3). Administration of hexaphosphate inositol noticeably reduced tumor incidence (50%, 12 mice with tumors out of 24 total), tumor multiplicity (0.8 ± 0.9) and tumor volume (12.3 ± 4.1 mm 3); however, the results were not statistically significant (P > 0.05). Further mechanistic studies showed that the inhibition of UC-associated carcinogenesis by inositol compounds might relate to their function on the modulation of macrophage mediated inflammation, nitro-oxidative stress and cell proliferation in UC-associated carcinogenesis. This study indicates that inositol compounds may have the potential to serve as preventive agents for chronic inflammation-carcinogenesis.

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