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Article

Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1
Department of Experimental Oncology, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigl, 53-114 Wroclaw, Poland
2
Łukasiewicz Research Network-Industrial Chemistry Institute, 8 Rydygiera, 01-793 Warsaw, Poland
3
Department of Bioanalysis and Drug Analysis, Faculty of Pharmacy, Medical University of Warsaw, 1 Banacha, 02-097 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Wojciech Jóźwicki
Int. J. Mol. Sci. 2021, 22(5), 2781; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052781
Received: 30 January 2021 / Revised: 3 March 2021 / Accepted: 4 March 2021 / Published: 9 March 2021
1,25-Dihydroxycholecalciferol, the hormonally active vitamin D3 metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)2D3 analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR. View Full-Text
Keywords: breast cancer; vitamin D analog; estrogen receptor; aromatase; anastrozole; mice breast cancer; vitamin D analog; estrogen receptor; aromatase; anastrozole; mice
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MDPI and ACS Style

Filip-Psurska, B.; Psurski, M.; Anisiewicz, A.; Libako, P.; Zbrojewicz, E.; Maciejewska, M.; Chodyński, M.; Kutner, A.; Wietrzyk, J. Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models. Int. J. Mol. Sci. 2021, 22, 2781. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052781

AMA Style

Filip-Psurska B, Psurski M, Anisiewicz A, Libako P, Zbrojewicz E, Maciejewska M, Chodyński M, Kutner A, Wietrzyk J. Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models. International Journal of Molecular Sciences. 2021; 22(5):2781. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052781

Chicago/Turabian Style

Filip-Psurska, Beata, Mateusz Psurski, Artur Anisiewicz, Patrycja Libako, Ewa Zbrojewicz, Magdalena Maciejewska, Michał Chodyński, Andrzej Kutner, and Joanna Wietrzyk. 2021. "Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models" International Journal of Molecular Sciences 22, no. 5: 2781. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22052781

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