Vitamin D signalling pathways in cancer: potential for anticancer therapeutics

Abstract

Epidemiological studies indicate that vitamin D insufficiency could have an aetiological role in various human cancers. Preclinical research indicates that the active metabolite of vitamin D, 1alpha,25(OH)2D3, also known as calcitriol, or vitamin D analogues might have potential as anticancer agents because their administration has antiproliferative effects, can activate apoptotic pathways and inhibit angiogenesis. In addition, 1alpha,25(OH)2D3 potentiates the anticancer effects of many cytotoxic and antiproliferative anticancer agents. Here, we outline the epidemiological, preclinical and clinical studies that support the development of 1alpha,25(OH)2D3 and vitamin D analogues as preventative and therapeutic anticancer agents.

Recent Candidate Molecular Markers: Vitamin D Signaling and Apoptosis Specific Regulator of p53 (ASPP) in Breast Cancer

“…In the first step 7-dehydrocholesterol is converted into vitamin D 3 in the skin after exposures to UV radiation. Vitamin (Deeb et al, 2007). Degradation of unneeded 1α 25(OH) 2 D 3 is accomplished by the enzyme CYP24A1 (24 Hydroxylase) for regulation of 1α 25( OH) 2 D 3 synthesis.…”

SPROUTY-2 and E-cadherin regulate reciprocally and dictate colon cancer cell tumourigenicity

“…Many epidemiological and animal studies indicate that the active vitamin D metabolite 1a, 25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) affords protection against colon cancer (Campbell and Adorini, 2006;Deeb et al, 2007;Eelen et al, 2007). A causal link between vitamin D deficiency and colon cancer has recently been considered probable by the International Agency for Research on Cancer (IARC, 2008).…”

MicroRNAs from biology to future pharmacotherapy: Regulation of cytochrome P450s and nuclear receptors

“…1,25-Dihydroxyvitamin D 3 (calcitriol) has now received much interest for its anti-tumor activity (Deeb et al, 2007), although it is well known as a regulator of calcium and bone homeostasis. Most of the biological effects of calcitriol are elicited by the binding to VDR (Carlberg and Polly, 1998).…”

“…Calcitriol is then inactivated by CYP24, a key metabolic enzyme, 9 the expression of which is regulated by VDR (Chen and DeLuca, 1995). It has been reported that CYP24 (Deeb et al, 2007) and VDR (Friedrich et al, 2002;Khadzkou et al, 2006) are overexpressed in various cancers. We found that both human CYP24 and VDR ) are post-transcriptionally regulated by miR-125b.…”