Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity

Scoparone, a natural compound isolated from Artemisia capillaris, has been used in Chinese herbal medicine to treat neonatal jaundice. Signal transducer and activator of transcription 3 (STAT3) contributes to the growth and survival of many human tumors. This study was undertaken to investigate the...

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Bibliographic Details
Published in:PloS one 2013-11, Vol.8 (11), p.e80391
Main Authors: Kim, Jeong-Kook, Kim, Joon-Young, Kim, Han-Jong, Park, Keun-Gyu, Harris, Robert A, Cho, Won-Jea, Lee, Jae-Tae, Lee, In-Kyu
Format: Article
Language:English
Subjects:
Agar
Aging
Androgens
Animals
Antibiotics
Anticancer properties
Antineoplastic Agents - pharmacology
Antitumor agents
Apoptosis
Artemisia - chemistry
Bcl-2 protein
Breast cancer
c-Myc protein
Cancer
Cancer cells
Cancer prevention
Cancer research
Cancer therapies
Cell cycle
Cell Cycle Checkpoints - drug effects
Cell Line, Tumor
Cell proliferation
Cell Proliferation - drug effects
Computer applications
Coumarins - pharmacology
Cyclin D1
Cyclin D1 - metabolism
Cytokines
Epidermal growth factor
G1 phase
G1 Phase - drug effects
HCT116 Cells
HeLa Cells
Hep G2 Cells
Herbal medicine
HT29 Cells
Humans
Inhibition
Inhibitor of Apoptosis Proteins - metabolism
Interleukin 6
Interleukin-6 - metabolism
Internal medicine
Janus kinase
Janus kinase 2
Janus Kinase 2 - metabolism
Jaundice
Kinases
Male
MCF-7 Cells
Medicine
Metabolism
Metastasis
Mice
Mice, Inbred BALB C
Mice, Nude
Mouse devices
Myc protein
Natural products
Neonates
Phosphorylation
Phosphorylation - drug effects
Prostate cancer
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - metabolism
Proteins
Proto-Oncogene Proteins c-bcl-2 - metabolism
Proto-Oncogene Proteins c-myc - metabolism
Rodents
Signal Transduction - drug effects
Stat3 protein
STAT3 Transcription Factor - antagonists & inhibitors
Suppressor of Cytokine Signaling 3 Protein
Suppressor of Cytokine Signaling Proteins - metabolism
Survivin
Transcription (Genetics)
Transcription activation
Transcription, Genetic - drug effects
Transfection
Tumors
Xenografts
Xenotransplantation
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Summary:Scoparone, a natural compound isolated from Artemisia capillaris, has been used in Chinese herbal medicine to treat neonatal jaundice. Signal transducer and activator of transcription 3 (STAT3) contributes to the growth and survival of many human tumors. This study was undertaken to investigate the anti-tumor activity of scoparone against DU145 prostate cancer cells and to determine whether its effects are mediated by inhibition of STAT3 activity. Scoparone inhibited proliferation of DU145 cells via cell cycle arrest in G1 phase. Transient transfection assays showed that scoparone repressed both constitutive and IL-6-induced transcriptional activity of STAT3. Western blot and quantitative real-time PCR analyses demonstrated that scoparone suppressed the transcription of STAT3 target genes such as cyclin D1, c-Myc, survivin, Bcl-2, and Socs3. Consistent with this, scoparone decreased phosphorylation and nuclear accumulation of STAT3, but did not reduce phosphorylation of janus kinase 2 (JAK2) or Src, the major upstream kinases responsible for STAT3 activation. Moreover, transcriptional activity of a constitutively active mutant of STAT3 (STAT3C) was inhibited by scoparone, but not by AG490, a JAK2 inhibitor. Furthermore, scoparone treatment suppressed anchorage-independent growth in soft agar and tumor growth of DU145 xenografts in nude mice, concomitant with a reduction in STAT3 phosphorylation. Computational modeling suggested that scoparone might bind the SH2 domain of STAT3. Our findings suggest that scoparone elicits an anti-tumor effect against DU145 prostate cancer cells in part through inhibition of STAT3 activity.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0080391