Kinetin riboside preferentially induces apoptosis by modulating Bcl-2 family proteins and caspase-3 in cancer cells.
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.
Choi
Bo-Hwa
BH
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637511, Singapore.
Kim
Wanil
W
Wang
Qiuxia Chelsia
QC
Kim
Dong-Chan
DC
Tan
Swee Ngin
SN
Yong
Jean Wan Hong
JW
Kim
Kyong-Tai
KT
Yoon
Ho Sup
HS
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis*; D002417:Cattle; D002460:Cell Line; D045744:Cell Line, Tumor; D045304:Cytochromes c / Q000378:metabolism; D005347:Fibroblasts; D006801:Humans; D007701:Kinetin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D051025:bcl-Associated Death Protein; C527965:kinetin riboside; D045304:Cytochromes c; D053148:Caspase 3; D000241:Adenosine; D007701:Kinetin