Camalexin-induced apoptosis in prostate cancer cells involves alterations of expression and activity of lysosomal protease cathepsin D.

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.

• Authors: Basil Smith, Diandra Randle, Roman Mezencev, LeeShawn Thomas, Cimona Hinton, Valerie Odero-Marah
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 19 Issue 4 Pg. 3988-4005 (Apr 02 2014) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 24699144 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents, Phytogenic
• BAX protein, human
• Indoles
• Plant Extracts
• Thiazoles
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• camalexin
• Poly(ADP-ribose) Polymerases
• CTSD protein, human
• Cathepsin D

Topics

• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Arabidopsis (chemistry)
• Cathepsin D (genetics, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Enzyme Activation (drug effects)
• Gene Expression Regulation (drug effects)
• Humans
• Indoles (isolation & purification, pharmacology)
• Lysosomes (drug effects, metabolism)
• Male
• Organ Specificity
• Oxidative Stress
• Plant Extracts (chemistry)
• Poly(ADP-ribose) Polymerases (genetics, metabolism)
• Prostate (drug effects, enzymology, pathology)
• Signal Transduction
• Thiazoles (isolation & purification, pharmacology)
• Tumor Suppressor Protein p53 (genetics, metabolism)
• bcl-2-Associated X Protein (genetics, metabolism)