Novel 19-nor-hexafluoride vitamin D3 analog (Ro 25-6760) inhibits human colon cancer in vitro via apoptosis.

  • Authors:
    • S R Evans
    • V Soldatenkov
    • E B Shchepotin
    • E Bogrash
    • I B Shchepotin
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  • Published online on: May 1, 1999     https://doi.org/10.3892/ijo.14.5.979
  • Pages: 979-1064
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Abstract

Our previously performed experiments clearly showed a significant VDR-mediated growth inhibitory effect of 1,25-dihydroxyvitamin D3 and its synthetic analogs in a variety of human cancer cells including human colon and breast cancer, soft tissue sarcoma, and malignant melanoma cell lines. The mechanisms by which 1, 25-dihydroxyvitamin D3 and its synthetic analogs growth inhibit human cancer cells is poorly elucidated. The exposure of human colon cancer cells HT-29 to 1,25-dihydroxyvitamin D3 or its analog, 1alpha, 25-dihydroxy-16-ene-23yne-26,27-hexafluoro-19-nor-choleca lci ferol (Ro 25-6760), at the 10(-6) M concentration resulted in significant growth inhibition with induction of the apoptotic process after three days of treatment detected by TUNEL assay and agarose gel electrophoresis of DNA. As a logical link with DNA fragmentation analyses and TUNEL assay, cleavage of the 116 kDa PARP protein was accompanied by the appearance of a characteristic 85 kDa fragment of PARP in a population of floating cells after both treatments. The results of cell cycle analysis showed a G0/G1 phase block after three days of administration of either compound when compared with untreated cells. On day 4, G0/G1 cell cycle arrest remained on the same level in comparison with control. Paralleling the G0/G1 phase block, was a notable decrease in the number of cells in the S phase which also became significant after three days of treatment. The results of these experiments show that the newly developed 19-nor synthetic vitamin D3 analog, Ro 25-6760, as well as 1, 25-dihydroxyvitamin D3, induced the expression of p21waf1, resulted in a significant G1/G0 cell cycle arrest leading to impressive growth inhibition and induction of apoptosis associated with proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) showing a possible involvement of apoptosis-specific activation of the ICE/CED-3 proteolitic pathway.

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May 1999
Volume 14 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Evans, S., Soldatenkov, V., Shchepotin, E., Bogrash, E., & Shchepotin, I. (1999). Novel 19-nor-hexafluoride vitamin D3 analog (Ro 25-6760) inhibits human colon cancer in vitro via apoptosis.. International Journal of Oncology, 14, 979-1064. https://doi.org/10.3892/ijo.14.5.979
MLA
Evans, S., Soldatenkov, V., Shchepotin, E., Bogrash, E., Shchepotin, I."Novel 19-nor-hexafluoride vitamin D3 analog (Ro 25-6760) inhibits human colon cancer in vitro via apoptosis.". International Journal of Oncology 14.5 (1999): 979-1064.
Chicago
Evans, S., Soldatenkov, V., Shchepotin, E., Bogrash, E., Shchepotin, I."Novel 19-nor-hexafluoride vitamin D3 analog (Ro 25-6760) inhibits human colon cancer in vitro via apoptosis.". International Journal of Oncology 14, no. 5 (1999): 979-1064. https://doi.org/10.3892/ijo.14.5.979