interventional strategies to mitigate body weight gain and its sequelae ( Blüher 2019 ). Vitamin A or retinol is a fat-soluble vitamin with long recognized roles in vision, growth, reproduction, and immunity. An expanding body of evidence further implicates
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Aprajita S Yadav, Nina Isoherranen, and Katya B Rubinow
P Viganò, D Lattuada, S Mangioni, L Ermellino, M Vignali, E Caporizzo, P Panina-Bordignon, M Besozzi, and A M Di Blasio
Introduction Vitamin D is a major regulator of mineral ion homeostasis by facilitating calcium and phosphate uptake in the gut and by modulating bone cell development and action ( Kumar 1980 , Jones et al. 1998 ). However, the
T Ichikawa, K Horie-Inoue, K Ikeda, B Blumberg, and S Inoue
Introduction Vitamin Ks are fat-soluble 2-methyl-1,4-naphthoquinone-related compounds, including natural phylloquinone (K 1 ) and menaquinones (K 2 ). Vitamins K 1 and K 2 differ only in the substituent group. Vitamin K 1 possesses a phytyl group
S M Jeyakumar, A Vajreswari, B Sesikeran, and N V Giridharan
continuous recruitment of newer cells and elimination of adipocytes by apoptosis under normal physiological conditions as well as disease conditions. Vitamin A, an important micronutrient, has an unusually wide range of vital physiological actions in
Maria K Tsoumpra, Shun Sawatsubashi, Michihiro Imamura, Seiji Fukumoto, Shin’ichi Takeda, Toshio Matsumoto, and Yoshitsugu Aoki
Introduction The biologically active metabolite of vitamin D, 1,25-dihydroxyvitamin D 3 (VD3), is a calcium regulating hormone that exerts its tissue-specific biological actions through binding to its intracellular vitamin D receptor (VDR
R F Chun, M Gacad, L Nguyen, M Hewison, and J S Adams
and vitamin D receptors; VDRs), it seems unlikely that the process of binding a specific ligand will depend simply on localized concentration gradients. Whereas the mechanisms that define the intracellular localization and movement of receptor proteins
Vincent Giguère
from organs and biological fluids that had profound effects on reproduction, development, and general maintenance of a healthy organism. Coincidently, the chemical structure of vitamin A and the steroid hormones estradiol and progesterone were resolved
M J Campbell, E Elstner, S Holden, M Uskokovic, and H P Koeffler
ABSTRACT
We have synthesized and studied the ability of a series of seven novel 1α,25(OH)2 vitamin D3 analogues to inhibit clonal growth of prostate cancer cells (LNCaP, PC-3 and DU-145). Addition of double and triple bonds to the C/D ring (C-16) and side chain (C-22 and C-23) as well as lengthening of the side chain were important for enhanced activity against LNCaP and PC-3. Reorientation of the side chain in the 20-epi configuration resulted in analogues that were extremely potent only against LNCaP (ED50 ≈ 5 × 10−11 m). Compounds with six fluorines on the end of the side chain were very active against both PC-3 and LNCaP (ED50 ≈ 2 × 10−8 m). DU-145 cells were relatively resistant to compounds with all of these modifications, but removal of C-19 (e.g. 1,25(OH)2-16-ene-23-yne-26,27-F6-19-nor-D3) resulted in an analogue that was inhibitory against all three prostate cell lines. Further analysis showed that pulse exposure (3 days, 10−7 m) to this analogue was enough to inhibit clonal growth of PC-3 cells by 50%. The same exposure also induced cell cycle arrest of all three cell lines, accompanied by upregulated protein expression of the cyclin-dependent kinase inhibitor (CDKI) known as p21 waf1 in all three cell lines, and the CDKI known as p27 kip1 in LNCaP cells. Associated with upregulation of these CDKIs, partial differentiation occurred as measured by increased expression of both prostate-specific antigen by LNCaP cells and E-cadherin, a cell adhesion protein that may act as a putative tumour suppressor (LNCaP and PC-3 cells). In summary, this is the first report of a potent series of 19-nor-vitamin D3 analogues with the ability to inhibit proliferation of LNCaP, PC-3 and DU-145 prostate cancer cell lines. These compounds may mediate their potent anti-proliferative activities through a cell cycle arrest pathway.
Andrea Hanel, Henna-Riikka Malmberg, and Carsten Carlberg
Introduction The micronutrient vitamin D 3 is known best as a key regulator of calcium homeostasis, which is essential for proper bone formation ( van de Peppel & van Leeuwen 2014 , Carmeliet et al . 2015 ). Interestingly, the nuclear
Lorraine J Gudas
Introduction and focus Vitamin A (all-trans retinol, ROL), a lipid-soluble micronutrient, is absolutely required for mammalian life. Without vitamin A, mammals develop many clinical pathologies, from xerophthalmia (dryness and inflammation of
