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Effects of kinetin riboside on proliferation and proapoptotic activities in human normal and cancer cell lines.

Abstract
Kinetin riboside (KR) is a N6-substituted derivative of adenosine. It is a natural compound which occurs in the milk of coconuts on the nanomole level. KR was initially shown to selectively inhibit proliferation of cancer cells and induce their apoptosis. We observed that KR inhibited growth (20-80%) of not only human cancer, but also normal cells and that this effect strongly depended on the type of cells. The anti-apoptotic Bcl-2 protein was downregulated, while proapoptotic Bax was upregulated in normal as well as in cancer cell lines, upon exposure to KR. Cytochrome c level increased in the cytosol upon treatment of cells with KR. The activity of caspases (ApoFluor®Green Caspase Activity Assay), as well as caspase-3 (caspase-3 activation assay) were increased mainly in cancer cells. The expression of procaspase 9 and its active form in the nucleus as well as in cytosol of KR-treated cells was elevated. In contrast, no effect of KR on caspase 8 expression was noted. The results indicated that non-malignant cells were less sensitive to KR then their cancer analogs and that KR most likely stimulated apoptosis mechanism of cancer cells through the intrinsic pathway.
AuthorsPaulina Dudzik, Joanna Dulińska-Litewka, Eliza Wyszko, Patrycja Jędrychowska, Maciej Opałka, Jan Barciszewski, Piotr Laidler
JournalJournal of cellular biochemistry (J Cell Biochem) Vol. 112 Issue 8 Pg. 2115-24 (Aug 2011) ISSN: 1097-4644 [Electronic] United States
PMID21465535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 Wiley-Liss, Inc.
Chemical References
  • BAX protein, human
  • bcl-2-Associated X Protein
  • kinetin riboside
  • Cytochromes c
  • CASP3 protein, human
  • Caspase 3
  • Caspase 8
  • Adenosine
  • Kinetin
Topics
  • Adenosine (pharmacology)
  • Apoptosis (drug effects)
  • Caspase 3 (biosynthesis)
  • Caspase 8 (biosynthesis)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cytochromes c (metabolism)
  • Gene Expression Regulation, Enzymologic (drug effects)
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Humans
  • Kinetin (pharmacology)
  • Neoplasms (metabolism)
  • bcl-2-Associated X Protein (metabolism)

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