26,26,26,27,27,27-Hexadeuterated-1,25-Dihydroxyvitamin D3 (1,25D-d6) As Adjuvant of Chemotherapy in Breast Cancer Cell Lines

Cancers

Samuel Seoane³  Maria A. Bermudez³  Juan Sendon-Lago³  Anxo Martinez-Ordo༞z³  Soraya Abdul-Hadi¹  Miguel Maestro²  Antonio Mouriño² 

[1] University of Puerto Rico, Recinto de Rio Piedras, Avda. Barbosa-Ponce de Leon, San Juan 23301, Puerto Rico; E-Mail:;Department of Organic Chemistry, School of Chemistry, Research Laboratory Ignacio Ribas, Avda. das Ciencias s/n, University of Santiago de Compostela, Santiago de Compostela 15782, Spain; E-Mails:;Department of Physiology-CIMUS, Endocrine Oncology Laboratories (P1L3), Avda. Barcelona s/n, Campus Vida-University of Santiago de Compostela, Santiago de Compostela 15782, Spain; E-Mails:

关键词: 1α;    25-dihydroxyvitamin D₃;    26;    26;    26;    27;    27;    27-hexadeuterated 1α;    25-dihydroxyvitamin D₃;    vitamin D;    deuterated vitamin D;    chemotheraphy;    breast cancer;   

DOI  :  10.3390/cancers6010067

来源: mdpi

【 摘 要 】

It has been demonstrated that 1,25-dihydroxyvitamin D₃ (1,25D) and some of its analogues have antitumor activity. 1,25D labeled with deuterium (26,26,26,27,27,27-hexadeuterated 1α,25-dihydroxyvitamin D₃, or 1,25D-d₆) is commonly used as internal standard for 1,25D liquid chromatography-mass spectrometry (LC-MS) quantification. In the present study using human breast cancer cell lines, the biological activity of 1,25D-d₆ administered alone and in combination with two commonly used antineoplastic agents, 5-fluorouracil and etoposide, was evaluated. Using an MTT assay, flow cytometry, and western blots, our data demonstrated that 1,25D-d₆ has effects similar to the natural hormone on cell proliferation, cell cycle, and apoptosis. Furthermore, the combination of 1,25D-d₆ and etoposide enhances the antitumoral effects of both compounds. Interestingly, the antitumoral effect is higher in the more aggressive MDA-MB-231 breast cancer cell line. Our data indicate that 1,25D-d₆ administered alone or in combination with chemotherapy could be a good experimental method for accurately quantifying active 1,25D levels in cultures or in biological fluids, on both in vitro breast cancer cell lines and in vivo animal experimental models.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.