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VMY-1-103, a Dansylated Analog of Purvalanol B, Induces caspase-3-dependent Apoptosis in LNCaP Prostate Cancer Cells

VMY-1-103, a Dansylated Analog of Purvalanol B, Induces caspase-3-dependent Apoptosis in LNCaP Prostate Cancer Cells

Lymor Ringer, Paul Sirajuddin, Venkata Mahidhar Yenugonda, Anup Ghosh, Kyle Divito, Valerie Trabosh, Yesha Patel, Amanda Brophy, Scott Grindrod, Michael P Lisanti, Dean Rosenthal, Milton L Brown, Maria Laura Avantaggiati, etc.

Cancer Biol Ther. 2010 Aug 15;10(4):320-5.

PMID: 20574155

Abstract:

The 2,6,9-trisubstituted purine group of cyclin dependent kinase inhibitors have the potential to be clinically relevant inhibitors of cancer cell proliferation. We have recently designed and synthesized a novel dansylated analog of purvalanol B, termed VMY-1-103, that inhibited cell cycle progression in breast cancer cell lines more effectively than did purvalanol B and allowed for uptake analyses by fluorescence microscopy. ErbB-2 plays an important role in the regulation of signal transduction cascades in a number of epithelial tumors, including prostate cancer (PCa). Our previous studies demonstrated that transgenic expression of activated ErbB-2 in the mouse prostate initiated PCa and either the overexpression of ErbB-2 or the addition of the ErbB-2/ErbB-3 ligand, heregulin (HRG), induced cell cycle progression in the androgen-responsive prostate cancer cell line, LNCaP. In the present study, we tested the efficacy of VMY-1-103 in inhibiting HRG-induced cell proliferation in LNCaP prostate cancer cells. At concentrations as low as 1 μM, VMY-1-103 increased both the proportion of cells in G(1) and p21(CIP1) protein levels. At higher concentrations (5 μM or 10 μM), VMY-1-103 induced apoptosis via decreased mitochondrial membrane polarity and induction of p53 phosphorylation, caspase-3 activity and PARP cleavage. Treatment with 10 μM Purvalanol B failed to either influence proliferation or induce apoptosis. Our results demonstrate that VMY-1-103 was more effective in inducing apoptosis in PCa cells than its parent compound, purvalanol B, and support the testing of VMY-1-103 as a potential small molecule inhibitor of prostate cancer in vivo.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP212844547	Purvalanol B		212844-54-7	Price

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