Toxicity and antitumor activity of the vitamin D analogs PRI-1906 and PRI-1907 in combined treatment with cyclophosphamide in a mouse mammary cancer model

Cancer Chemotherapy and Pharmacology
Joanna WietrzykAndrzej Kutner

Abstract

Active and less toxic vitamin D analogs could be useful for clinical applications. In the present study, we evaluated the toxicity and antitumor effect of two new synthetic analogs of vitamin D, namely PRI-1906 [(24E)-24a-Homo-(1S)-1,25-dihydroxyergocalciferol] and its side-chain unsaturated homo analog PRI-1907. The toxicity and calcemic activity, as well as antitumor effect of calcitriol analogs was investigated in vivo. The studies were performed in a mouse mammary 16/C cancer model. Since calcitriol and its analogs inhibited 16/C tumor growth only slightly, we applied them in the combined therapy with cyclophosphamide (CY). Moreover, cell cycle analysis and VDR and p27 expression were investigated. The LD50 values after five daily subcutaneous (s.c.) injections were 7.8, 10.0 and 2.4 microg/kg per day for calcitriol, PRI-1906 and PRI-1907, respectively. The serum calcium level increased to 40, 23 and 63% over the control for these compounds. We also compare the antitumor activity of the PRI-1906 with the calcitriol and previously studied PRI-2191 (1,24-dihydroxyvitamin D3, tacalcitol). Statistically significant inhibition of tumor growth by calcitriol up to the eighth day was observed in all schedules applied. PRI-1906 inhi...Continue Reading

References

Oct 1, 1991·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·K OzonoJ W Pike
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J LiaoJ W Pike
Apr 13, 1989·The New England Journal of Medicine·H ReichelA W Norman
Apr 1, 1995·Endocrine Reviews·R BouillonA W Norman
Oct 21, 1998·The Journal of Steroid Biochemistry and Molecular Biology·E MarcinkowskaC Radzikowski
Jun 1, 2000·Current Pharmaceutical Design·A OpolskiA Kutner
Sep 29, 2000·Pharmacology & Therapeutics·G J PetersS P Ackland
Oct 31, 2001·Seminars in Oncology·T M BeerW D Henner
Dec 24, 2002·Clinical Pharmacology and Therapeutics·Josephia R MuindiDonald L Trump
Jun 19, 2003·Journal of the National Cancer Institute·Takashi KumagaiH Phillip Koeffler
Jul 4, 2003·The Journal of Nutrition·JoEllen WelshCarmen J Narvaez
Jul 4, 2003·The Journal of Nutrition·Donna M PeehlDavid Feldman
Aug 2, 2003·Nature Reviews. Cancer·Sergio A Lamprecht, Martin Lipkin
Aug 6, 2003·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Anthony W NormanWilliam H Okamura
Aug 6, 2003·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Aruna V KrishnanDavid Feldman
Aug 6, 2003·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Josef EliasInge Schuster
Jan 25, 2005·Molecular and Cellular Endocrinology·Jennifer A WietzkeJoEllen Welsh
May 25, 2005·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Lorraine C LoweKay W Colston
Mar 7, 2006·Journal of Cellular Biochemistry·Hsuen-Tsen ChengWen-Chun Hung

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Citations

Jun 13, 2014·Oncology Reports·Magdalena MilczarekJoanna Wietrzyk
Oct 23, 2015·International Journal of Molecular Sciences·Justyna TryndaJoanna Wietrzyk
Mar 17, 2010·The Journal of Steroid Biochemistry and Molecular Biology·B FilipA Kutner
Jul 25, 2015·Journal of Experimental & Clinical Cancer Research : CR·Bassem RefaatAthar Khojah
Nov 19, 2015·International Journal of Molecular Sciences·Ewa MajJoanna Wietrzyk
Jul 3, 2013·Steroids·Anita PietraszekAndrzej Kutner
Oct 30, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Agnieszka KotlarzSergiusz Markowicz
Apr 4, 2021·International Journal of Molecular Sciences·Beata Filip-PsurskaJoanna Wietrzyk

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