Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line.

Thomas, M. G.; Tebbutt, S.; Williamson, R. C. N.

doi:10.1136/gut.33.12.1660

Cited by 93 publications

(64 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2). Upon binding to the VDR, 1,25(OH)2D3 decreases the proliferation of a variety of human colon cancer cell lines (23,24) as well as of cells within resected human rectal mucosa (25). Moreover, VDR-null mice exhibit decreased markers of cellular proliferation and increased levels of markers reflecting DNA oxidative stress (26), suggesting that the vitamin D-receptor complex acts by attenuating oxidative DNA damage and preventing malignant transformation from occurring.…”

Section: Discussionmentioning

confidence: 99%

Expression of Vitamin D Receptor and 25-Hydroxyvitamin D3-1α-Hydroxylase in Normal and Malignant Human Colon

Matusiak

Murillo

Carroll

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

113

View full text Add to dashboard Cite

Considerable evidence exists to support the use of vitamin D to prevent and/or treat colorectal cancer. However, the routine use of bioactive vitamin D, 1,25-dihydroxyvitamin D3, is limited by the side effect of toxic hypercalcemia. Recent studies, however, suggest that colonic epithelial cells express 25-hydroxyvitamin D3-1A-hydroxylase, an enzyme that converts nontoxic pro-vitamin D, 25-hydroxycholecalciferol [25(OH)D3], to its bioactive form. Yet, nothing is known as to the cellular expression of 1A-hydroxylase and the vitamin D receptor (VDR) in the earliest histopathologic structures associated with malignant transformation such as aberrant crypt foci (ACF) and polyps [addressing the possibility of using nontoxic 25(OH)D3 for chemoprevention], nor is anything known as to the expression of these proteins in colorectal cancer as a function of tumor cell differentiation or metastasis [relevant to using 25(OH)D3 for chemotherapy]. In this study, we show that 1A-hydroxylase is present at equal high levels in normal colonic epithelium as in ACFs, polyps, and colorectal cancer irrespective of tumor cell differentiation. In contrast, VDR levels were low in normal colonic epithelial cells; were increased in ACFs, polyps, and well-differentiated tumor cells; and then declined as a function of tumor cell de-differentiation. Both 1A-hydroxylase and VDR levels were negligible in tumor cells metastasizing to regional lymph nodes. Overall, these data support using 25(OH)D3 for colorectal cancer chemoprevention but suggest that provitamin D is less likely to be useful for colorectal cancer chemotherapy. (Cancer Epidemiol Biomarkers Prev 2005;14(10):2370-6)

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of Vitamin D Receptor and 25-Hydroxyvitamin D3-1α-Hydroxylase in Normal and Malignant Human Colon

Matusiak

Murillo

Carroll

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

113

View full text Add to dashboard Cite

show abstract

“…Surprisingly, 1␣,25-(OH) 2 D 3 treatment of Caco2 and HT29 cells dramatically induces Nox1 mRNA levels, while cell proliferation is diminished. 1␣,25-(OH) 2 D 3 , an inhibitor of colon cancer cell proliferation, also induces differentiation markers in Caco2 cells (19,20). This active vitamin D 3 metabolite may have a direct role in colon epithelial cell proliferation, since animals fed vitamin D-deficient diets exhibit colon epithelial hyperproliferation (26).…”

Section: Discussionmentioning

confidence: 99%

NAD(P)H Oxidase 1, a Product of Differentiated Colon Epithelial Cells, Can Partially Replace Glycoprotein 91phox in the Regulated Production of Superoxide by Phagocytes

Geiszt

Lekstrom

Brenner

et al. 2003

The Journal of Immunology

183

168

View full text Add to dashboard Cite

Reactive oxygen species (ROS) serve several physiological functions; in some settings they act in host defense, while in others they function in cellular signaling or in biosynthetic reactions. We studied the expression and function of a recently described source of ROS, NAD(P)H oxidase 1 or Nox1, which has been associated with cell proliferation. In situ hybridization in mouse colon revealed high Nox1 expression within the lower two-thirds of colon crypts, where epithelial cells undergo proliferation and differentiation. Human multitumor tissue array analysis confirmed colon-specific Nox1 expression, predominantly in differentiated epithelial tumors. Differentiation of Caco2 and HT29 cells with 1α,25-dihydroxyvitamin D3 or IFN-γ enhances Nox1 expression and decreases cell proliferation, suggesting that Nox1 does not function as a mitogenic oxidase in colon epithelial cells. Transduction with retrovirus encoding Nox1 restored activation and differentiation-dependent superoxide production in gp91phox-deficient PLB-985 cells, indicating close functional similarities to the phagocyte oxidase (phox). Furthermore, coexpression of cytosolic components, p47phox and p67phox, augments Nox1 activity in reconstituted K562 cells. Finally, Nox1 partially restores superoxide production in neutrophils differentiating ex vivo from gp91phox-deficient CD34+ peripheral blood-derived stem cells derived from patients with X-linked chronic granulomatous disease. These studies demonstrate a significant functional homology (cofactor-dependent and activation-regulated superoxide production) between Nox1 and its closest homologue, gp91phox, suggesting that targeted up-regulation of Nox1 expression in phagocytic cells could provide a novel approach in the molecular treatment of chronic granulomatous disease.

show abstract

“…Polymorphisms of the VDR gene also have been studied in conjunction with colorectal cancer and adenomas because VDR may play a key role in vitamin D signaling, cell proliferation, and differentiation [23][24][25][26][27][28]50]. The VDR appears to be an important link in CRC etiology, possibly because it plays a role in both insulin and inflammation-related pathways and is at a point of convergence of these two important pathways [51][52][53].…”

Section: Discussionmentioning

confidence: 99%

IL6 genotypes and colon and rectal cancer

Slattery

Wolff

Herrick

et al. 2007

Cancer Causes Control

View full text Add to dashboard Cite

Inflammation appears to play a key role in the development of colorectal cancer (CRC). In this study we examine factors involved in the regulation of inflammation and risk of CRC. Data from a multicenter case-control study of colon (N = 1579 cases and N = 1977 controls) and rectal (N = 794 cases and N = 1005 controls) cancer were used to evaluate the association between the rs1800795 and rs1800796 IL6 polymorphisms and CRC. We evaluated the joint effects of IL6 single nucleotide polymorphisms and regular use of aspirin/NSAIDs and vitamin D receptor (VDR) genotype. Having a C allele of the rs1800796 IL6 polymorphisms and the GG genotype of the rs1800795 IL6 polymorphisms was associated with a statistically significantly reduced the risk of colon (OR 0.76 95% CI 0.57, 1.00), but not rectal (OR 1.49 95% CI 1.02,2.16) cancer. Both IL6 polymorphisms were associated with significant interaction with current use of aspirin/NSAIDs to alter risk of colon cancer: individuals with a C allele in either polymorphism who were current users of aspirin/NSAIDs had the lowest colon cancer risk. CRC risk also was associated with an interaction between VDR and IL6 genotypes that was modified by current use of aspirin/NSAIDs. This study provides further support for inflammation-related factors in the etiology of CRC. Other studies are needed to explore other genes in this and other inflammation-related pathways.

show abstract

Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line.

Cited by 93 publications

References 29 publications

Expression of Vitamin D Receptor and 25-Hydroxyvitamin D3-1α-Hydroxylase in Normal and Malignant Human Colon

Expression of Vitamin D Receptor and 25-Hydroxyvitamin D3-1α-Hydroxylase in Normal and Malignant Human Colon

NAD(P)H Oxidase 1, a Product of Differentiated Colon Epithelial Cells, Can Partially Replace Glycoprotein 91phox in the Regulated Production of Superoxide by Phagocytes

IL6 genotypes and colon and rectal cancer

Contact Info

Product

Resources

About