Kinetin Riboside Preferentially Induces Apoptosis by Modulating Bcl-2 Family Proteins and caspase-3 in Cancer Cells

Cancer Lett. 2008 Mar 8;261(1):37-45. doi: 10.1016/j.canlet.2007.11.014. Epub 2007 Dec 26.

Abstract

Here, we demonstrate that kinetin riboside (KR), a cytokinin analog, induces apoptosis in HeLa and mouse melanoma B16F-10 cells. KR disrupted the mitochondrial membrane potential and induced the release of cytochrome c and activation of caspase-3. Bad were upregulated while Bcl-2 was down-regulated under KR exposure. A tumor growth in mice was dramatically suppressed by KR. In contrast, human skin fibroblast CCL-116 and bovine primary fibroblast cells show resistances to KR and no significant changes in Bad, Bcl-X(L,) and cleaved PARP were observed. Our data suggest that KR selectively induces apoptosis in cancer cells through the classical mitochondria dependent apoptosis pathway.

MeSH terms

  • Adenosine / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Caspase 3 / biosynthesis*
  • Cattle
  • Cell Line
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Fibroblasts
  • Humans
  • Kinetin / pharmacology*
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • bcl-Associated Death Protein / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • bcl-Associated Death Protein
  • kinetin riboside
  • Cytochromes c
  • Caspase 3
  • Adenosine
  • Kinetin