Purvalanol A is a specific CDK inhibitor which triggers apoptosis by causing cell cycle arrest in
cancer cells. Although it has strong apoptotic potential, the mechanistic action of
Purvalanol A on significant cell signaling targets has not been clarified yet.
Polyamines are crucial metabolic regulators affected by CDK inhibition because of their role in cell cycle progress as well. In addition, malignant cells possess impaired
polyamine homeostasis with high level of intracellular
polyamines. Especially induction of
polyamine catabolic
enzymes spermidine/
spermine N1-acetyltransferase (SSAT),
polyamine oxidase (PAO) and
spermine oxidase (SMO) induced toxic by-products in correlation with the induction of apoptosis in
cancer cells. In this study, we showed that
Purvalanol A induced apoptosis in
caspase- dependent manner in MCF-7 ER(+) cells, while MDA-MB-231 (ER-) cells were less sensitive against
drug. In addition Bcl-2 is a critical target for
Purvalanol A, since Bcl-2 overexpressed cells are more resistant to
Purvalanol A-mediated apoptosis. Furthermore, exposure of MCF-7 cells to
Purvalanol A triggered SSAT and PAO upregulation and the presence of PAO/SMO inhibitor, MDL 72,527 prevented
Purvalanol A-induced apoptosis.