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Molecules 2014, 19(4), 3988-4005; doi:10.3390/molecules19043988
Article

Camalexin-Induced Apoptosis in Prostate Cancer Cells Involves Alterations of Expression and Activity of Lysosomal Protease Cathepsin D

1, 1, 2, 3, 1 and 1,*
1 Center for Cancer Research and Therapeutic development, Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, USA 2 Department of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA 3 Department of Biological Sciences, Florida A & M University, Tallahassee, FL 32307, USA
* Author to whom correspondence should be addressed.
Received: 7 January 2014 / Revised: 5 March 2014 / Accepted: 5 March 2014 / Published: 2 April 2014
(This article belongs to the Special Issue Phytoalexins: Current Progress and Future Prospects)
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Abstract

Camalexin, the phytoalexin produced in the model plant Arabidopsis thaliana, possesses antiproliferative and cancer chemopreventive effects. We have demonstrated that the cytostatic/cytotoxic effects of camalexin on several prostate cancer (PCa) cells are due to oxidative stress. Lysosomes are vulnerable organelles to Reactive Oxygen Species (ROS)-induced injuries, with the potential to initiate and or facilitate apoptosis subsequent to release of proteases such as cathepsin D (CD) into the cytosol. We therefore hypothesized that camalexin reduces cell viability in PCa cells via alterations in expression and activity of CD. Cell viability was evaluated by MTS cell proliferation assay in LNCaP and ARCaP Epithelial (E) cells, and their respective aggressive sublines C4-2 and ARCaP Mesenchymal (M) cells, whereby the more aggressive PCa cells (C4-2 and ARCaPM) displayed greater sensitivity to camalexin treatments than the lesser aggressive cells (LNCaP and ARCaPE). Immunocytochemical analysis revealed CD relocalization from the lysosome to the cytosol subsequent to camalexin treatments, which was associated with increased protein expression of mature CD; p53, a transcriptional activator of CD; BAX, a downstream effector of CD, and cleaved PARP, a hallmark for apoptosis. Therefore, camalexin reduces cell viability via CD and may present as a novel therapeutic agent for treatment of metastatic prostate cancer cells.
Keywords: camalexin; prostate cancer; lysosomes; cathepsin D; phytoalexins camalexin; prostate cancer; lysosomes; cathepsin D; phytoalexins
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Smith, B.; Randle, D.; Mezencev, R.; Thomas, L.; Hinton, C.; Odero-Marah, V. Camalexin-Induced Apoptosis in Prostate Cancer Cells Involves Alterations of Expression and Activity of Lysosomal Protease Cathepsin D. Molecules 2014, 19, 3988-4005.

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