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.