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Vitamin d and pancreatic cancer-an update.

Chiang KC, Yeh CN, Chen TC - Cancers (Basel) (2011)

Bottom Line: The non-classical actions of vitamin D, namely anti-proliferation, pro-differentiation, immune function modulation, and anti-inflammation, have received great attention during the past decade, in particular, the potential of vitamin D analogs alone or in combination with other anticancer agents for the treatment of a variety of cancers.The association between vitamin D status and the higher incidence of many forms of cancer has suggested that vitamin D may play a role in the etiology of these types of cancer.Although it is still controversial whether this association exists for pancreatic cancer, biochemical evidence clearly indicates pancreatic cancer cells are responsive to the inhibitory effect of vitamin D and its analogs.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taiwan. taichen@bu.edu.

ABSTRACT
The non-classical actions of vitamin D, namely anti-proliferation, pro-differentiation, immune function modulation, and anti-inflammation, have received great attention during the past decade, in particular, the potential of vitamin D analogs alone or in combination with other anticancer agents for the treatment of a variety of cancers. The association between vitamin D status and the higher incidence of many forms of cancer has suggested that vitamin D may play a role in the etiology of these types of cancer. Although it is still controversial whether this association exists for pancreatic cancer, biochemical evidence clearly indicates pancreatic cancer cells are responsive to the inhibitory effect of vitamin D and its analogs. In this review, we discuss briefly the origin and current therapy of pancreatic cancer, the history, source, metabolism and functions of vitamin D, the recent progress in the epidemiological studies of sunlight, and vitamin D status, and biochemical studies of vitamin D analogs in the prevention and treatment of pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus

Vitamin D sources, metabolism, mechanism of action and biological activities. Vitamin D3 (cholecalciferol) is either derived from the diet, including supplements, or synthesized in the skin via sunlight exposure (290-315 nm) from the precursor 7-dehydrocholesterol (7-DHC). Vitamin D3 is initially hydroxylated in the liver by vitamin D-25-hydroxylase (25-OHase) to generate the circulating prohormone 25-hydroxyvitamin D3 [25(OH)D3]. The subsequent conversion of 25(OH)D3 to the active form, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], occurs in the kidneys catalyzed by a tightly regulated enzyme 25(OH)D-1α-hydroxylase (1α-OHase or CYP27B1). However, the activation may take place in many extra-renal tissues, including pancreas, bone, breast, colon, prostate, etc. The extra-renal synthesis of 1α,25(OH)2D may be one reason why serum 25(OH)D level, instead of the circulating level of the active form, 1α,25(OH)2D, is the index of vitamin D nutritional status. The resulting 1α,25(OH)2D3 elicits its transcriptional effects by binding to the vitamin D receptor (VDR)/retinoid X receptor (RXR) complex on vitamin D response element (VDRE) in the promoter region of vitamin D responsive genes. The cellular effects include anti-proliferation, pro-differentiation, pro-apoptosis, anti-inflammation, immune response regulation, etc. In addition to 25-OHase and 1α-OHase, 24-OHase (CYP24A1) also plays an important role in the vitamin D metabolic cascade, and thereby, in the regulation of vitamin D actions. The primary role of 24-OHase is to hydroxylate 1α,25(OH)2D3 and 25(OH)D3 to their corresponding 24-hydroxylated metabolites, the first step of vitamin D catabolic pathway to inactivate VDR ligands.
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f1-cancers-03-00213: Vitamin D sources, metabolism, mechanism of action and biological activities. Vitamin D3 (cholecalciferol) is either derived from the diet, including supplements, or synthesized in the skin via sunlight exposure (290-315 nm) from the precursor 7-dehydrocholesterol (7-DHC). Vitamin D3 is initially hydroxylated in the liver by vitamin D-25-hydroxylase (25-OHase) to generate the circulating prohormone 25-hydroxyvitamin D3 [25(OH)D3]. The subsequent conversion of 25(OH)D3 to the active form, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], occurs in the kidneys catalyzed by a tightly regulated enzyme 25(OH)D-1α-hydroxylase (1α-OHase or CYP27B1). However, the activation may take place in many extra-renal tissues, including pancreas, bone, breast, colon, prostate, etc. The extra-renal synthesis of 1α,25(OH)2D may be one reason why serum 25(OH)D level, instead of the circulating level of the active form, 1α,25(OH)2D, is the index of vitamin D nutritional status. The resulting 1α,25(OH)2D3 elicits its transcriptional effects by binding to the vitamin D receptor (VDR)/retinoid X receptor (RXR) complex on vitamin D response element (VDRE) in the promoter region of vitamin D responsive genes. The cellular effects include anti-proliferation, pro-differentiation, pro-apoptosis, anti-inflammation, immune response regulation, etc. In addition to 25-OHase and 1α-OHase, 24-OHase (CYP24A1) also plays an important role in the vitamin D metabolic cascade, and thereby, in the regulation of vitamin D actions. The primary role of 24-OHase is to hydroxylate 1α,25(OH)2D3 and 25(OH)D3 to their corresponding 24-hydroxylated metabolites, the first step of vitamin D catabolic pathway to inactivate VDR ligands.

Mentions: 1α,25(OH)2D exerts its hormone-like functions through binding to vitamin D receptor (VDR), an endocrine member of the nuclear receptor superfamily [57] to regulate its target genes (Figure 1). A study, in which a Chip-sequencing method was applied to define genome-wide mapping of VDR binding, reported that VDR was bound to 2,776 genomic sites in 229 vitamin D-regulated genes [58]. Since VDR was first identified in 1979 in many tissues not known for regulating calcium and bone metabolism [59], it is not surprising that 1α,25(OH)2D may possess functions beyond its originally identified action on calcium homeostasis and bone mineralization. It is now well-established that 1α,25(OH)2D exhibits anti-proliferative, pro-differentiating, anti-inflammatory, and pro-apoptotic activities in a tissue- and cell-specific manner [55,60-62] and, so far, it has been shown to have growth inhibitory effect on prostate, colon, breast, lung, liver and pancreatic cancer cells, which express VDR [47,63-67].


Vitamin d and pancreatic cancer-an update.

Chiang KC, Yeh CN, Chen TC - Cancers (Basel) (2011)

Vitamin D sources, metabolism, mechanism of action and biological activities. Vitamin D3 (cholecalciferol) is either derived from the diet, including supplements, or synthesized in the skin via sunlight exposure (290-315 nm) from the precursor 7-dehydrocholesterol (7-DHC). Vitamin D3 is initially hydroxylated in the liver by vitamin D-25-hydroxylase (25-OHase) to generate the circulating prohormone 25-hydroxyvitamin D3 [25(OH)D3]. The subsequent conversion of 25(OH)D3 to the active form, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], occurs in the kidneys catalyzed by a tightly regulated enzyme 25(OH)D-1α-hydroxylase (1α-OHase or CYP27B1). However, the activation may take place in many extra-renal tissues, including pancreas, bone, breast, colon, prostate, etc. The extra-renal synthesis of 1α,25(OH)2D may be one reason why serum 25(OH)D level, instead of the circulating level of the active form, 1α,25(OH)2D, is the index of vitamin D nutritional status. The resulting 1α,25(OH)2D3 elicits its transcriptional effects by binding to the vitamin D receptor (VDR)/retinoid X receptor (RXR) complex on vitamin D response element (VDRE) in the promoter region of vitamin D responsive genes. The cellular effects include anti-proliferation, pro-differentiation, pro-apoptosis, anti-inflammation, immune response regulation, etc. In addition to 25-OHase and 1α-OHase, 24-OHase (CYP24A1) also plays an important role in the vitamin D metabolic cascade, and thereby, in the regulation of vitamin D actions. The primary role of 24-OHase is to hydroxylate 1α,25(OH)2D3 and 25(OH)D3 to their corresponding 24-hydroxylated metabolites, the first step of vitamin D catabolic pathway to inactivate VDR ligands.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756357&req=5

f1-cancers-03-00213: Vitamin D sources, metabolism, mechanism of action and biological activities. Vitamin D3 (cholecalciferol) is either derived from the diet, including supplements, or synthesized in the skin via sunlight exposure (290-315 nm) from the precursor 7-dehydrocholesterol (7-DHC). Vitamin D3 is initially hydroxylated in the liver by vitamin D-25-hydroxylase (25-OHase) to generate the circulating prohormone 25-hydroxyvitamin D3 [25(OH)D3]. The subsequent conversion of 25(OH)D3 to the active form, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], occurs in the kidneys catalyzed by a tightly regulated enzyme 25(OH)D-1α-hydroxylase (1α-OHase or CYP27B1). However, the activation may take place in many extra-renal tissues, including pancreas, bone, breast, colon, prostate, etc. The extra-renal synthesis of 1α,25(OH)2D may be one reason why serum 25(OH)D level, instead of the circulating level of the active form, 1α,25(OH)2D, is the index of vitamin D nutritional status. The resulting 1α,25(OH)2D3 elicits its transcriptional effects by binding to the vitamin D receptor (VDR)/retinoid X receptor (RXR) complex on vitamin D response element (VDRE) in the promoter region of vitamin D responsive genes. The cellular effects include anti-proliferation, pro-differentiation, pro-apoptosis, anti-inflammation, immune response regulation, etc. In addition to 25-OHase and 1α-OHase, 24-OHase (CYP24A1) also plays an important role in the vitamin D metabolic cascade, and thereby, in the regulation of vitamin D actions. The primary role of 24-OHase is to hydroxylate 1α,25(OH)2D3 and 25(OH)D3 to their corresponding 24-hydroxylated metabolites, the first step of vitamin D catabolic pathway to inactivate VDR ligands.
Mentions: 1α,25(OH)2D exerts its hormone-like functions through binding to vitamin D receptor (VDR), an endocrine member of the nuclear receptor superfamily [57] to regulate its target genes (Figure 1). A study, in which a Chip-sequencing method was applied to define genome-wide mapping of VDR binding, reported that VDR was bound to 2,776 genomic sites in 229 vitamin D-regulated genes [58]. Since VDR was first identified in 1979 in many tissues not known for regulating calcium and bone metabolism [59], it is not surprising that 1α,25(OH)2D may possess functions beyond its originally identified action on calcium homeostasis and bone mineralization. It is now well-established that 1α,25(OH)2D exhibits anti-proliferative, pro-differentiating, anti-inflammatory, and pro-apoptotic activities in a tissue- and cell-specific manner [55,60-62] and, so far, it has been shown to have growth inhibitory effect on prostate, colon, breast, lung, liver and pancreatic cancer cells, which express VDR [47,63-67].

Bottom Line: The non-classical actions of vitamin D, namely anti-proliferation, pro-differentiation, immune function modulation, and anti-inflammation, have received great attention during the past decade, in particular, the potential of vitamin D analogs alone or in combination with other anticancer agents for the treatment of a variety of cancers.The association between vitamin D status and the higher incidence of many forms of cancer has suggested that vitamin D may play a role in the etiology of these types of cancer.Although it is still controversial whether this association exists for pancreatic cancer, biochemical evidence clearly indicates pancreatic cancer cells are responsive to the inhibitory effect of vitamin D and its analogs.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Chang Gung Memorial Hospital and Chang Gung University, Taiwan. taichen@bu.edu.

ABSTRACT
The non-classical actions of vitamin D, namely anti-proliferation, pro-differentiation, immune function modulation, and anti-inflammation, have received great attention during the past decade, in particular, the potential of vitamin D analogs alone or in combination with other anticancer agents for the treatment of a variety of cancers. The association between vitamin D status and the higher incidence of many forms of cancer has suggested that vitamin D may play a role in the etiology of these types of cancer. Although it is still controversial whether this association exists for pancreatic cancer, biochemical evidence clearly indicates pancreatic cancer cells are responsive to the inhibitory effect of vitamin D and its analogs. In this review, we discuss briefly the origin and current therapy of pancreatic cancer, the history, source, metabolism and functions of vitamin D, the recent progress in the epidemiological studies of sunlight, and vitamin D status, and biochemical studies of vitamin D analogs in the prevention and treatment of pancreatic cancer.

No MeSH data available.


Related in: MedlinePlus