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26,26,26,27,27,27-Hexadeuterated-1,25-Dihydroxyvitamin D3 (1,25D-d6) As Adjuvant of Chemotherapy in Breast Cancer Cell Lines
Department of Physiology-CIMUS, Endocrine Oncology Laboratories (P1L3), Avda. Barcelona s/n, Campus Vida-University of Santiago de Compostela, Santiago de Compostela 15782, Spain
University of Puerto Rico, Recinto de Rio Piedras, Avda. Barbosa-Ponce de Leon, San Juan 23301, Puerto Rico
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
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 28 October 2013; in revised form: 2 December 2013 / Accepted: 16 December 2013 / Published: 27 December 2013
Abstract: 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 1a,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.
Keywords: 1a,25-dihydroxyvitamin D3; 26,26,26,27,27,27-hexadeuterated 1a,25-dihydroxyvitamin D3; vitamin D; deuterated vitamin D; chemotheraphy; breast cancer
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Seoane, S.; Bermudez, M.A.; Sendon-Lago, J.; Martinez-Ordoñez, A.; Abdul-Hadi, S.; Maestro, M.; Mouriño, A.; Perez-Fernandez, R. 26,26,26,27,27,27-Hexadeuterated-1,25-Dihydroxyvitamin D3 (1,25D-d6) As Adjuvant of Chemotherapy in Breast Cancer Cell Lines. Cancers 2014, 6, 67-78.
Seoane S, Bermudez MA, Sendon-Lago J, Martinez-Ordoñez A, Abdul-Hadi S, Maestro M, Mouriño A, Perez-Fernandez R. 26,26,26,27,27,27-Hexadeuterated-1,25-Dihydroxyvitamin D3 (1,25D-d6) As Adjuvant of Chemotherapy in Breast Cancer Cell Lines. Cancers. 2014; 6(1):67-78.
Seoane, Samuel; Bermudez, Maria A.; Sendon-Lago, Juan; Martinez-Ordoñez, Anxo; Abdul-Hadi, Soraya; Maestro, Miguel; Mouriño, Antonio; Perez-Fernandez, Roman. 2014. "26,26,26,27,27,27-Hexadeuterated-1,25-Dihydroxyvitamin D3 (1,25D-d6) As Adjuvant of Chemotherapy in Breast Cancer Cell Lines." Cancers 6, no. 1: 67-78.