VMY-1-103, a dansylated analog of purvalanol B, induces caspase-3-dependent apoptosis in LNCaP prostate cancer cells

The Potential Target Therapy of Prostate Cancer Stem Cells

“…It was also observed that VMY-1-103 induced apoptosis via decreased mitochondrial membrane polarity, induced p53 phosphorylation, caspase-3 activation, and PARP cleavage in these prostatic tumor cells, which express p53 wild type. More, VMY-1-103 was also effective inducing cell cycle arrest in prostate cancer cell lines compromised for p53 function, however, VMY-1-103 failed to induce apoptosis in p53-null prostate cell lines PC3 (Ringer et al, 2010). These results, strongly suggest that VMY-1-103 may be an effective therapeutic, either alone or in combinations with other drugs, in treating prostate cancer.…”

“…Therefore, inhibitors of cell cycle regulatory proteins has become an area of increased interest in targeting both cancer cells per se and CSCs (Malumbres & Barbacid, 2009). For example, we have recently demonstrated the efficacy of a novel dansylated VMY-1-103, a CDK1, CDK2 inhibitor, based on purvalanol B (Ringer et al, 2010), at very low concentrations in inhibiting Erb-2/Erb-3/heregulin-induced cell proliferation in LNCaP prostate cancer cells. It was also observed that VMY-1-103 induced apoptosis via decreased mitochondrial membrane polarity, induced p53 phosphorylation, caspase-3 activation, and PARP cleavage in these prostatic tumor cells, which express p53 wild type.…”

Stem Cells and Prostate Cancer

“…It was also observed that VMY-1-103 induced apoptosis via decreased mitochondrial membrane polarity; and induced p53 phosphorylation, caspase-3 activation, and PARP cleavage in these PC cells, which do express endogen wild type p53. But, VMY-1-103 failed to induce apoptosis in the p53-null PC cell line PC3 [124]. These results, strongly suggest that VMY-1-103 may be an effective therapeutic agent, either alone or in combinations with other drugs, in treating PC.…”

“…The cyclin-dependent kinase inhibitor VMY-1-103 inhibited at very low concentrations the Erb-2/Erb-3/heregulin-induced cell proliferation in LNCaP PC cells. [124]. It was also observed that VMY-1-103 induced apoptosis via decreased mitochondrial membrane polarity; and induced p53 phosphorylation, caspase-3 activation, and PARP cleavage in these PC cells, which do express endogen wild type p53.…”

Downregulation of c-Myc mediated ODC expression after purvalanol treatment is under control of upstream MAPK signaling axis in MCF-7 breast cancer cells

“…Olomoucine, roscovitine, and purvalanol are the most commonly investigated CDK inhibitors that cause cell cycle arrest and trigger apoptotic cell death. Roscovitine (CYC202, Seliciclib) or purvalanol induce apoptosis by causing cell cycle arrest in the G1 and G2/M phases in prostate (Ringer et al, 2010), lung (Zhang et al, 2010), multiple myeloma (Komina et al, 2011), colon, and breast cancer cell lines (Wesierska-Gadek et al, 2004;Arisan et al, 2012). Although CDK inhibitor-induced apoptotic cell death has been determined in breast cancer, the exact underlying molecular targets in cell death and survival mechanism have not been clarified yet.…”