Inhibition of fatty acid synthase expression by 1α,25-dihydroxyvitamin D3 in prostate cancer cells

Vitamin D3 inhibits fatty acid synthase expression by stimulating the expression of long‐chain fatty‐acid‐CoA ligase 3 in prostate cancer cells

“…These suggest that the downregulation of FAS expression by vitamin D 3 is mediated by FACL3 in LNCaP cells. This is consistent with our previous findings that the action of vitamin D 3 on FAS expression is not direct [15]. In vitamin D 3 -responsive human prostate cancer PC3 cells, which are androgen receptor-negative in contrast to LNCaP cells, no regulation of FAS expression by vitamin D 3 was found, consistent with no vitamin D 3 regulation of FACL3 expression in PC3 cells.…”

“…A difference of p < 0:05 was considered as significant. [15]. We also found that FACL3 mRNA and activity were increased by vitamin D 3 in LNCaP cells [14].…”

“…In our previous studies, we investigated the genes regulated by 1a,25(OH) 2 D 3 in prostate cancer LNCaP cells using cDNA microarray and found that two fatty acid metabolic enzymes, FAS and FACL3, were regulated by vitamin D 3 . The further studies suggested that FAS and FACL3 were involved in vitamin D 3 inhibition of LNCaP cells growth [14,15]. FAS catalytically synthesizes fatty acid and FACL3, a downstream enzyme of FAS, converts long chain fatty acid to the corresponding acyl-CoA.…”

Hipervitaminose D em animais

“…A suplementação com níveis adequados de vitamina D também diminui a incidência de doenças cardiovasculares (Holick 2004, Zitterman 2006. Nos últimos anos, muito se tem testado "in vitro" a ação anti-neoplásica da vitamina D em tumores, como o retinoblastoma (Wagner et al 2003), o carcinoma prostático (Qiao et al 2003) e até mesmo "in vivo", como o osteossarcoma experimentalmente implantado em ratos gnotobióticos (Barroga et al 2000). Uma vez que receptores de vitamina D estão presentes em linfócitos T e B e macrófagos ativados, a prevenção de doenças auto--imunes, incluindo diabetes tipo I, artrite reumatóide e esclerose múltipa têm sido possível através da suplementação com esse composto (Holick 2004).…”

Adaptive evolution of the human fatty acid synthase gene: Support for the cancer selection and fat utilization hypotheses?

“…By inhibiting MAP and PI-3 kinases, SREBP1 levels are downregulated and transcription of the FAS promoter is decreased, thereby reducing fatty acid synthesis in cancer cells (Yang et al, , 2003. FAS regulation is likely to be of major significance in the treatment of cancers (Kumar-Sinha et al, 2003;Qiao et al, 2003). If positive selection for novel FAS genotypes has been a major contributor to the evolution of the human lineage, it should be possible to identify this situation.…”