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The phytoalexin camalexin mediates cytotoxicity towards aggressive prostate cancer cells via reactive oxygen species

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Abstract

Camalexin is a phytoalexin that accumulates in various cruciferous plants upon exposure to environmental stress and plant pathogens. Besides moderate antibacterial and antifungal activity, camalexin was reported to also exhibit antiproliferative and cancer chemopreventive effects in breast cancer and leukemia. We studied the cytotoxic effects of camalexin treatment on prostate cancer cell lines and whether this was mediated by reactive oxygen species (ROS) generation. As models, we utilized LNCaP and its aggressive subline, C4-2, as well as ARCaP cells stably transfected with empty vector (Neo) control or constitutively active Snail cDNA that represents an epithelial to mesenchymal transition (EMT) model and displays increased cell migration and tumorigenicity. We confirmed previous studies showing that C4-2 and ARCaP-Snail cells express more ROS than LNCaP and ARCaP-Neo, respectively. Camalexin increased ROS, decreased cell proliferation, and increased apoptosis more significantly in C4-2 and ARCaP-Snail cells as compared to LNCaP and ARCaP-Neo cells, respectively, while normal prostate epithelial cells (PrEC) were unaffected. Increased caspase-3/7 activity and increased cleaved PARP protein shown by Western blot analysis was suggestive of increased apoptosis. The ROS scavenger N-acetyl cysteine (NAC) antagonized the effects of camalexin, whereas the addition of exogenous hydrogen peroxide potentiated the effects of camalexin, showing that camalexin is mediating its effects through ROS. In conclusion, camalexin is more potent in aggressive prostate cancer cells that express high ROS levels, and this phytoalexin has a strong potential as a novel therapeutic agent for the treatment of especially metastatic prostate cancer.

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Abbreviations

EMT:

Epithelial to mesenchymal transition

ROS:

Reactive oxygen species

NAC:

N-acetyl cysteine

H2 DCFDA:

2′,7′-dichlorodihydrofluorescein diacetate

H2O2 :

Hydrogen peroxide

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Acknowledgments

This work was supported by NIH grants 5P20MD002285 (V.A.O.M) and 8G12MD007590-26 (V.A.O.M.).

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Authors and Affiliations

  1. The Department of Biological Sciences, Center for Cancer Research and Therapeutic Development, Clark Atlanta University, 223 James P. Brawley Drive SW, Atlanta, GA, 30314, USA

    Basil A. Smith, Corey L. Neal, Mahandranauth Chetram, BaoHan Vo, Cimona Hinton & Valerie A. Odero-Marah

  2. Department of Biology, Georgia Institute of Technology, Atlanta, GA, USA

    Roman Mezencev

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  1. Basil A. Smith
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Correspondence to Valerie A. Odero-Marah.

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Smith, B.A., Neal, C.L., Chetram, M. et al. The phytoalexin camalexin mediates cytotoxicity towards aggressive prostate cancer cells via reactive oxygen species. J Nat Med 67, 607–618 (2013). https://doi.org/10.1007/s11418-012-0722-3

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  • DOI: https://doi.org/10.1007/s11418-012-0722-3

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