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Plumbagin, a Medicinal Plant–Derived Naphthoquinone, Is a Novel Inhibitor of the Growth and Invasion of Hormone-Refractory Prostate Cancer
- Source :
- Cancer Research. 68:9024-9032
- Publication Year :
- 2008
- Publisher :
- American Association for Cancer Research (AACR), 2008.
-
Abstract
- Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men. Hormone-refractory invasive PCa is the end stage and accounts for the majority of PCa patient deaths. We present here that plumbagin (PL), a quinoid constituent isolated from the root of the medicinal plant Plumbago zeylanica L., may be a potential novel agent in the control of hormone-refractory PCa. Specific observations are the findings that PL inhibited PCa cell invasion and selectively induced apoptosis in PCa cells but not in immortalized nontumorigenic prostate epithelial RWPE-1 cells. In addition, i.p. administration of PL (2 mg/kg body weight), beginning 3 days after ectopic implantation of hormone-refractory DU145 PCa cells, delayed tumor growth by 3 weeks and reduced both tumor weight and volume by 90%. Discontinuation of PL treatment in PL-treated mice for as long as 4 weeks did not result in progression of tumor growth. PL, at concentrations as low as 5 μmol/L, inhibited in both cultured PCa cells and DU145 xenografts (a) the expression of protein kinase Cε (PKCε), phosphatidylinositol 3-kinase, phosphorylated AKT, phosphorylated Janus-activated kinase-2, and phosphorylated signal transducer and activator of transcription 3 (Stat3); (b) the DNA-binding activity of transcription factors activator protein-1, nuclear factor-κB, and Stat3; and (c) Bcl-xL, cdc25A, and cyclooxygenase-2 expression. The results indicate for the first time, using both in vitro and in vivo preclinical models, that PL inhibits the growth and invasion of PCa. PL inhibits multiple molecular targets including PKCε, a predictive biomarker of PCa aggressiveness. PL may be a novel agent for therapy of hormone-refractory PCa. [Cancer Res 2008;68(21):9024–32]
- Subjects :
- Male
Cancer Research
Mice, Nude
Apoptosis
Electrophoretic Mobility Shift Assay
urologic and male genital diseases
Article
Mice
chemistry.chemical_compound
Prostate cancer
DU145
In vivo
medicine
Animals
Humans
Neoplasm Invasiveness
Phosphatidylinositol
STAT3
DNA Primers
Plants, Medicinal
Base Sequence
biology
Activator (genetics)
Prostatic Neoplasms
Plumbagin
medicine.disease
Immunohistochemistry
Molecular biology
Oncology
chemistry
biology.protein
Cancer research
Cell Division
Naphthoquinones
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....5e16036b4b4addc3e271e677651591ba