Year: 2012
Type: article
Abstract: 慈恵医大誌 2012；127：259-73. 1 東京慈恵会医科大学分子疫学研究室 2 株式会社ケムジェネシス開発本部 (受付 平成 24 年 8 月 15 日)1α,25-dihydroxyvitamin D3, which is the active form of vitamin D3, induces cancer cells to undergo apoptosis and differentiation and inhibits their growth.However, to date, no derivatives of active vitamin D3 have been used clinically as anticancer agents, because of the side effect of hypercalcemia.Accordingly, we experimentally searched for novel vitamin D3 derivatives that have anticancer effects but do not cause hypercalcemia.To search for anticancer effects, we examined 46 vitamin D3 derivatives, each with slight structural changes, during screening with HL60 human leukemia cells in vitro.The 50% inhibitory dose (ID50) is defined as the dose of an agent that inhibits tumor proliferation by 50% compared with a control solution.The ID50 for active vitamin D3 is 4 nM.The screening test determined that 20-epi-1α,25(OH)2D3 (VD01) and 20-epi-26,27-dihomo-1α,25(OH)2D3 (VD3), each with an ID50 of 0.07 nM, were the derivatives that most effectively inhibited the growth of tumors.We then created 20-epi-25(OH)D3 (VD47) and 20-epi-26,27dihomo-25(OH)D3 (VD48), which were derivatives that lacked the 1α-hydroxyl group of VD01 and VD03, respectively, and performed a similar screening test in vitro.Only VD48 was found to have anticancer effects (ID50 2.5-1.25 nM); VD47 did not show anticancer effects (ID50 < 40 nM).Next, we compared the effects of VD03 and VD48 in C.B-17/Icr-scid/scidJcl mice into which HL60 human leukemia cells had been transplanted to verify whether these derivatives have anticancer effects without causing hypercalcemia.Because all the mice treated with VD03 died before the tumor proliferated, the anticancer effects could not be evaluated in these mice, although hypercalcemia was detected.On the other hand, hypercalcemia was not detected in mice treated with VD48, but anticancer effects were not detected either, because the extent of tumor proliferation was similar to that in the control group.In the present study, none of the vitamin D3 derivatives examined had anticancer effects without causing hypercalcemia.
Authors: 野矢, 三樹, タメーズ, セリーナ, 土黒, 一郎, 浦島, 充佳
Institution: Jikei University School of Medicine
Language: Japanese
Topic: Vitamin D Research Studies
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W76169128
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