TY - JOUR
T1 - Biological evaluation of new vitamin D2 analogues
AU - Corcoran, Aoife
AU - Bermudez, Maria A.
AU - Seoane, Samuel
AU - Perez-fernandez, Roman
AU - Krupa, Małgorzata
AU - Pietraszek, Anita
AU - Chodyński, Michał
AU - Kutner, Andrzej
AU - Brown, Geoffrey.
AU - Marcinkowska, Ewa
PY - 2015/9/30
Y1 - 2015/9/30
N2 - 1,25-dihydroxyvitamin D3 (1,25D), a steroid hormone which regulates calcium/phosphate homeostasis, has a broad spectrum of anti-cancer activities, including differentiation of acute myeloid leukemia (AML) cells. In order to avoid undesirable side effects such as hypercalcemia, low-calcemic analogues should be produced for therapeutic purposes. In this paper, we describe biological activities of double-point modified analogues of vitamin D2 and we compare them to 1,25D and to paricalcitol, the drug used to treat secondary hyperparathyroidism. In vivo, our new analogues have lower calcemic effects, and lower toxicity in comparison to 1,25D. They have enhanced pro-differentiating and transcription-inducing activities in AML cells. Interestingly, differentiation effects do not correlate with the affinities of the analogues to the vitamin D receptor (VDR).
AB - 1,25-dihydroxyvitamin D3 (1,25D), a steroid hormone which regulates calcium/phosphate homeostasis, has a broad spectrum of anti-cancer activities, including differentiation of acute myeloid leukemia (AML) cells. In order to avoid undesirable side effects such as hypercalcemia, low-calcemic analogues should be produced for therapeutic purposes. In this paper, we describe biological activities of double-point modified analogues of vitamin D2 and we compare them to 1,25D and to paricalcitol, the drug used to treat secondary hyperparathyroidism. In vivo, our new analogues have lower calcemic effects, and lower toxicity in comparison to 1,25D. They have enhanced pro-differentiating and transcription-inducing activities in AML cells. Interestingly, differentiation effects do not correlate with the affinities of the analogues to the vitamin D receptor (VDR).
KW - vitamin D analogues
KW - vitamin D receptor
KW - leukemia
KW - differentiation
KW - calcemic effects
KW - keratinocytes
U2 - 10.1016/j.jsbmb.2015.09.033
DO - 10.1016/j.jsbmb.2015.09.033
M3 - Article
SN - 0960-0760
JO - The Journal of Steroid Biochemistry and Molecular Biology
JF - The Journal of Steroid Biochemistry and Molecular Biology
ER -