title: Pien Tze Huang suppresses IL-6-inducible STAT3 activation in human colon             carcinoma cells through induction of SOCS3.
abstract: IL-6/STAT3 is one of the most critical cellular signal transduction pathways             known to malfunction in colorectal cancer (CRC). As a target gene of signal transducer             and activator of transcription 3 (STAT3) signaling, suppressor of cytokine signaling             3 (SOCS3) can be quickly induced by interleukin-6 (IL-6) stimulation but it then             strongly inhibits IL-6-mediated STAT3 activation, functioning as a negative feedback             regulator of the IL-6/STAT3 pathway. Aberrant activation of STAT3 and/or reduced             expression of SOCS are strongly correlated with carcinogenesis, which therefore             becomes a promising target for the development of novel anticancer chemotherapies.             Pien Tze Huang (PZH) is a well-known traditional Chinese formula that was first             prescribed by a royal physician 450 years ago in the Ming Dynasty. It has been             used in China and Southeast Asia for centuries as a folk remedy for various types             of cancer including CRC. However, the precise mechanism of its antitumor activity             remains largely unclear. In the present study, we found that PZH could significantly             and dose-dependently inhibit IL-6-mediated increase of STAT3 phosphorylation levels             and transcriptional activity in the human colon carcinoma HT-29 cells, resulting             in the suppression of cell proliferation and the induction of apoptosis. In addition,             PZH treatment profoundly inhibited IL-6-induced upregulation of cyclin D1 and             Bcl-2, two key target genes of the STAT3 pathway. Moreover, PZH treatment increased             the expression of SOCS3. These results suggest that PZH could effectively inhibit             proliferation and promote apoptosis of human colon carcinoma cells via modulation             of the IL-6/STAT3 signaling pathway and its target genes.
authors.affiliation: Academy of Integrative Medicine Biomedical Research Center, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, PR China.
authors.forename: Aling
authors.initials: A
authors.lastname: Shen
authors.forename: Youqin
authors.initials: Y
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Hong
authors.forename: Jiumao
authors.initials: J
authors.lastname: Lin
authors.forename: Lihui
authors.initials: L
authors.lastname: Wei
authors.forename: Zhenfeng
authors.initials: Z
authors.lastname: Hong
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Sferra
authors.forename: Jun
authors.initials: J
authors.lastname: Peng
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019938:Cyclin D1 / Q000096:biosynthesis / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; 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; C539975:pien tze huang; D019938:Cyclin D1