Ormeloxifene, a nonsteroidal antifertility drug promotes megakaryocyte differentiation in leukemia cell line K562.
K562
apoptosis
caspase activation
megakaryocyte
myeloid differentiation
ormeloxifene
Journal
Cell biology international
ISSN: 1095-8355
Titre abrégé: Cell Biol Int
Pays: England
ID NLM: 9307129
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
revised:
27
01
2023
received:
05
07
2022
accepted:
09
03
2023
medline:
16
6
2023
pubmed:
24
3
2023
entrez:
23
3
2023
Statut:
ppublish
Résumé
Ormeloxifene (ORM) (3,4-trans-2,2-dimethyl-3-phenyl-4-p-(β-pyrrolidinoethoxy) phenyl-7-methoxychroman), world's first nonsteroidal selective estrogen receptor modulator approved for contraception in India has been shown to have potential anticancer activities. Here, we show that ORM can induce megakaryocyte and myeloid (granulocytic) but not erythroid differentiation in multipotent human myeloid leukemia cell line K562. We show that ORM at an IC50 of 7.5 µM can induce morphological changes similar to megakaryocytes in K562 cells. ORM led to increase in levels of megakaryocytic differentiation markers (CD41 and CD61) as well as key transcription factors GATA1 and AML1. We further show that ORM induces megakaryocytic differentiation in K562 cells through ERK activation and induction of autophagy in a fashion similar to other known inducers of megakaryocytic differentiation such as phorbol esters. In addition, as shown earlier, we yet again observed that ORM led to activation of caspases since their inhibition through pan-caspase inhibitor mitigated megakaryocytic differentiation as they led to significant decrease in CD41 and CD61. Because induction of megakaryocytic differentiation in K562 involves growth arrest and exit from cell cycle, we also observed an increase in levels of p21 and p27 with decrease in c-Myc protein levels in K562 cells treated with 7.5 µM ORM for 24 and 48 h, respectively. Taken together, these findings indicate that ORM can markedly induce megakaryocytic differentiation in K562 cells.
Substances chimiques
ormeloxifene
44AXY5VE90
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1247-1258Subventions
Organisme : Lady Tata Memorial Trust, Mumbai
ID : GAP0367
Informations de copyright
© 2023 International Federation for Cell Biology.
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