Sanguinarine is a compound derived from the bloodroot plant. A cell-based rapid screen of the Prestwick Chemical Library, which consists of 1,120 FDA-approved compounds with known safety and bioavailability data in humans, identified Sanguinarine. Sanguinarine inhibits survivin, a unique member of the inhibitor of apoptosis protein family. Survivin is the fourth most universally enhanced transriptome in cancer tissues.
In performing the screening, they selected compound that decreased DU145 cell viability by >50%, but decreased PZ-HPV7 prostate cell viability by <10%. Sanguinarine is a benzophenanthrene alkaloid used in toothpaste and mouthwash to prevent gingivitis and other inflammatory conditions of the mouth. The IC50 for the PZ-HPV7 cells was 3 times higher than for C4-2 and DU145 cells, with most cells killed at 4uM. To test whether sanguinarine facilitates the cytotoxicity of paclitaxel chemotherapy, DU145 cells were treated with 5nM paclitaxel with or without 0.5uM sanguinarine. Sanguinarine alone had little effect, but combined with taxol it induced significantly more cell death than taxol alone. Experiments showed that sanguinarine decreased the protein expression of survivin in a dose-dependent fashion, but had no effect on Bcl-2 and XIAP proteins. Sanguinarine induced cleavage of PARP at 5uM concentrations, consistent with cell death. However, the levels of survivin protein expression in PZ-HPV7 cells did not change, suggesting that the degree of survivin degradation may be responsible for the tumor-specific cytotoxic effects. Data showed that the effect of sanguinarine on survivin was not at the transcriptional level; rather there was degradation of survivin protein. This occurred via a proteasome-dependent pathway; specifically sanguinarine enhanced survivin degradation via the ubiquitin-proteasome system.
The investigators studied whether sanguinarine could inhibit in vivo tumor growth of DU145 cells. Mice began treatment with sanguinarine or control 3 days after tumor injection. No toxicity was seen, and sanguinarine-treated mice had significant inhibition of tumor growth starting at day 31 until day 56 when the experiment was terminated. These data suggest that sanguinarine, a compound used in dental products inhibits survivin via protein degradation and suppresses in vivo prostate cancer tumor growth.
Sun M, Lou W, Chun JY, Cho DS, Nadiminty N, Evans CP, Chen J, Yue J, Zhou Q, Gao AC
Genes Cancer. 2010 Mar 1;1(3):283-292
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