Anticancer effects of the novel 1α, 25-dihydroxyvitamin D3 hybrid analog QW1624F2-2 in human neuroblastoma

C. Damodar Reddy, Ratnakar Patti, Asha Guttapalli, John M. Maris, Niranjan Yanamandra, Aparna Rachamallu, Leslie N. Sutton, Peter C. Phillips, Gary H. Posner

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Vitamin D3 analogs are potential anti-cancer agents with theoretically wide therapeutic index, but there have been limited studies directed towards human neuroblastoma. The antiproliferative ability of the novel vitamin D3 hybrid analog QW-1624F2-2 (QW, 1-hydroxymethyl-16-ene-24, 24-F2-26, 27-bishomo-25-hydroxyvitamin D3) was examined in two human neuroblastoma-derived cell-lines. Analog QW inhibited cell-cycle progression of IMR5 cells with accumulation in G1 phase. QW induced the differentiation of CHP134 as evidenced by increased neurite length. These effects were accompanied by decreased expression of MYCN in both the cell-lines treated with QW. Furthermore, QW inhibited the migration of CHP134 cells in matrigel invasion assays, indicating its anti-invasive ability. In athymic nude mice, we found that QW was less calcemic than EB1089 (1α, 25-dihydroxy-22, 24-diene-24, 26,27-trishomovitamin D3). Systemic administration of QW in a mouse xenotransplantation model revealed that it is more effective than EB1089 in suppressing the growth of CHP134 flank tumors. In summary, the low-calcemic hybrid analog QW showed significant anti-tumor activity in vivo and thus exhibits potential as a novel cancer therapeutic.

Original languageEnglish
Pages (from-to)198-206
Number of pages9
JournalJournal of Cellular Biochemistry
Volume97
Issue number1
DOIs
StatePublished - 1 Jan 2006
Externally publishedYes

Keywords

  • Anticancer
  • Low-calcemic
  • Neuroblastoma
  • Vitamin D3 analog

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