We present here first time that
Plumbagin (PL), a medicinal plant-derived
1,4-naphthoquinone, inhibits the growth and
metastasis of human
prostate cancer (PCa) cells in an orthotopic xenograft mouse model. In this study, human PCa PC-3M-luciferase cells (2 × 10(6)) were injected into the prostate of athymic nude mice. Three days post cell implantation, mice were treated with PL (2 mg/kg body wt. i.p. five days in a week) for 8 weeks. Growth and
metastasis of PC-3M-luciferase cells was examined weekly by bioluminescence imaging of live mice. PL-treatment significantly (p = 0.0008) inhibited the growth of orthotopic xenograft
tumors. Results demonstrated a significant inhibition of
metastasis into liver (p = 0.037), but inhibition of
metastasis into the lungs (p = 0.60) and lymph nodes (p = 0.27) was not observed to be significant. These results were further confirmed by histopathology of these organs. Results of histopathology demonstrated a significant inhibition of
metastasis into lymph nodes (p = 0.034) and lungs (p = 0.028), and a trend to significance in liver (p = 0.075). None of the mice in the PL-treatment group showed PCa
metastasis into the liver, but these mice had small
metastasis foci into the lymph nodes and lungs. However, control mice had large metastatic foci into the lymph nodes, lungs, and liver. PL-caused inhibition of the growth and
metastasis of PC-3M cells accompanies inhibition of the expression of: 1) PKCĪµ, pStat3Tyr705, and pStat3Ser727, 2) Stat3 downstream target genes (
survivin and Bcl(xL)), 3) proliferative markers Ki-67 and
PCNA, 4) metastatic marker MMP9, MMP2, and uPA, and 5) angiogenesis markers CD31 and
VEGF. Taken together, these results suggest that PL inhibits
tumor growth and
metastasis of human PCa PC3-M-
luciferase cells, which could be used as a therapeutic agent for the prevention and treatment of human PCa.