title: Scoparone exerts anti-tumor activity against DU145 prostate cancer cells via inhibition of STAT3 activity.
abstract: 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.
authors.affiliation: Department of Biomedical Science, Graduate School, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Jeong-Kook
authors.initials: JK
authors.lastname: Kim
authors.forename: Joon-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Han-Jong
authors.initials: HJ
authors.lastname: Kim
authors.forename: Keun-Gyu
authors.initials: KG
authors.lastname: Park
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harris
authors.forename: Won-Jea
authors.initials: WJ
authors.lastname: Cho
authors.forename: Jae-Tae
authors.initials: JT
authors.lastname: Lee
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019306:Artemisia / Q000737:chemistry; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D019938:Cyclin D1 / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D045325:HCT116 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D000077022:Survivin; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; C530104:CCND1 protein, human; D003374:Coumarins; D051034:Inhibitor of Apoptosis Proteins; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; C106644:SOCS3 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D000077022:Survivin; D019938:Cyclin D1; D053614:Janus Kinase 2; C018145:scoparone