Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress

Kállay, Enikö; Bareis, Petra; Bajna, Erika; Kriwanek, Stefan; Bonner, Elisabeth; Toyokuni, Shinya; Cross, Heide S.

doi:10.1016/s0278-6915(02)00030-3

Cited by 100 publications

(74 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, vitamin D signals are frequently found to be downregulated during the late stages of cancer progression through overexpression of SNAIL or other unknown mechanisms. 44,45 These data suggest that vitamin D might exert a subtle oxidative stress, which could stimulate the detoxification mechanisms to protect cells from the subsequent stress challenges; yet cancer cells lose the 1,25-VD-induced detoxification responses, therefore, 1,25-VD acts as a pro-oxidant in cancer cells. Together, the cell microenvironment might contribute to the differential 1,25-VD actions, but detailed mechanisms need to be further investigated.…”

Section: Discussionmentioning

confidence: 99%

Protective role of 1α, 25‐dihydroxyvitamin D₃ against oxidative stress in nonmalignant human prostate epithelial cells

Bao

Ting

Hsu

et al. 2008

Intl Journal of Cancer

146

108

View full text Add to dashboard Cite

Overproduction of reactive oxygen species (ROS), through either endogenous or exogenous sources, could induce DNA damage, and accumulation of DNA damage might lead to multistep carcinogenesis. The antioxidative effects of vitamin D have been suggested by epidemiological and many in vitro and in vivo laboratory studies. While exploring the antioxidative effects of vitamin D in prostate cells, we found that the active form of vitamin D, 1a, 25-dihydroxyvitamin D 3 (1,25-VD), can protect nonmalignant human prostate epithelial cell lines, BPH-1 and RWPE-1, but not malignant human prostate epithelial cells, CWR22R and DU 145, from oxidative stress-induced cell death. Glucose-6-phosphate dehydrogenase (G6PD), a key antioxidant enzyme, was dose-and time-dependently induced by 1,25-VD. Mechanistic studies using chromatin immunoprecipitation (ChIP) assay revealed that a direct repeat-3 (DR3) vitamin D response element located in the first intron of the G6PD genome can be bound by liganded vitamin D receptor, thereby regulating G6PD gene expression. Increasing G6PD activity and glutathione level by 1,25-VD can scavenge cellular ROS. Moreover, the protective effects of 1,25-VD were abolished by dehydroepiandrosterone, a noncompetitive inhibitor of G6PD activity. Together, our results showed that 1,25-VD can protect nonmalignant prostate cells from oxidative stress-induced cell death by elimination of ROS-induced cellular injuries through transcriptional activation of G6PD activity. The antioxidative effect of vitamin D strengthens its roles in cancer chemoprevention and adds to a growing list of beneficial effects of vitamin D against cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Protective role of 1α, 25‐dihydroxyvitamin D₃ against oxidative stress in nonmalignant human prostate epithelial cells

Bao

Ting

Hsu

et al. 2008

Intl Journal of Cancer

146

108

View full text Add to dashboard Cite

show abstract

“…Vdr-deficient mice do not show a spontaneous increase in cancer but are more prone to oncogene-or carcinogen-induced tumours (reviewed in Bouillon et al (2008)). These animals display colonic crypt hyper-proliferation, and increased levels of DNA damage and oxidative stress in the Endocrine-Related Cancer (2012) 19 R51-R71 www.endocrinology-journals.org R61 intestine (Kállay et al 2001(Kállay et al , 2002. Recently, two teams have bred Vdr K/C and Apc min/C mice in order to evaluate the consequences of VDR deficiency on the initiation and development of intestinal cancer , Zheng et al 2012.…”

Section: Anti-tumoural Action Of Vitamin D In Animal Models Of Crcmentioning

confidence: 99%

Vitamin D and colon cancer

Перейра¹,

Larriba²,

Múñoz³

2012

Endocrine-Related Cancer

109

View full text Add to dashboard Cite

The most active vitamin D metabolite, 1α,25-dihydroxyvitamin D3(1,25(OH)2D3), is a pleiotropic hormone with wide regulatory actions. Classically, vitamin D deficiency was known to alter calcium and phosphate metabolism and bone biology. In addition, recent epidemiological and experimental studies support the association of vitamin D deficiency with a large variety of human diseases, and particularly with the high risk of colorectal cancer. By regulating the expression of many genes via several mechanisms, 1,25(OH)2D3induces differentiation, controls the detoxification metabolism and cell phenotype, sensitises cells to apoptosis and inhibits the proliferation of cultured human colon carcinoma cells. Consistently, 1,25(OH)2D3and several of its analogues decrease intestinal tumourigenesis in animal models. Molecular, genetic and clinical data in humans are scarce but they suggest that vitamin D is protective against colon cancer. Clearly, the available evidence warrants new, well-designed, large-scale trials to clarify the role of vitamin D in the prevention and/or therapy of this important neoplasia.

show abstract

“…In the human colon, normal epithelial cells and some cancer cells express VDR (Kállay et al, 2002). Furthermore, some colon cancer cells express 25-hydroxyvitamin D 3 -1a-hydroxylase and can thus synthesise 1,25(OH) 2 D 3 from its precursor ).…”

Section: Vdr and Colon Cancermentioning

confidence: 99%

SNAIL vs vitamin D receptor expression in colon cancer: therapeutics implications

Larriba

Múñoz

2005

Br J Cancer

View full text Add to dashboard Cite

Vitamin D analogues with reduced hypercalcemic activity are under clinical investigation for use against colon cancer and other neoplasias. However, only a subset of patients responds to this therapy, most probably due to loss of vitamin D receptor (VDR) expression during tumour progression. Recent data show that SNAIL transcription factor represses VDR expression, and thus abolishes the antiproliferative and prodifferentiation effects of VDR ligands in cultured cancer cells and their antitumour action in xenografted mice. Accordingly, upregulation of SNAIL in human colon tumours associates with downregulation of VDR. These findings suggest that SNAIL may be associated with loss of responsiveness to vitamin D analogues and may thus be used as an indicator of patients who are unlikely to respond to this therapy.

show abstract

Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress

Cited by 100 publications

References 18 publications

Protective role of 1α, 25‐dihydroxyvitamin D₃ against oxidative stress in nonmalignant human prostate epithelial cells

Protective role of 1α, 25‐dihydroxyvitamin D₃ against oxidative stress in nonmalignant human prostate epithelial cells

Vitamin D and colon cancer

SNAIL vs vitamin D receptor expression in colon cancer: therapeutics implications

Contact Info

Product

Resources

About

Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress

Cited by 100 publications

References 18 publications

Protective role of 1α, 25‐dihydroxyvitamin D3 against oxidative stress in nonmalignant human prostate epithelial cells

Protective role of 1α, 25‐dihydroxyvitamin D3 against oxidative stress in nonmalignant human prostate epithelial cells

Vitamin D and colon cancer

SNAIL vs vitamin D receptor expression in colon cancer: therapeutics implications

Contact Info

Product

Resources

About

Protective role of 1α, 25‐dihydroxyvitamin D₃ against oxidative stress in nonmalignant human prostate epithelial cells

Protective role of 1α, 25‐dihydroxyvitamin D₃ against oxidative stress in nonmalignant human prostate epithelial cells