title: Sophoraflavanone G induces apoptosis of human cancer cells by targeting upstream signals of STATs.
abstract: Aberrantly activated signal transducer and activator of transcription (STAT) proteins are implicated with human cancers and represent essential roles for cancer cell survival and proliferation. Therefore, the development of small-molecule inhibitors of STAT signaling bearing pharmacological activity has therapeutic potential for the treatment of human cancers. In this study, we identified sophoraflavanone G as a novel small-molecule inhibitor of STAT signaling in human cancer cells. Sophoraflavanone G inhibited tyrosine phosphorylation of STAT proteins in Hodgkin's lymphoma and tyrosine phosphorylation of STAT3 in solid cancer cells by inhibiting phosphorylation of the Janus kinase (JAK) proteins, Src family tyrosine kinases, such as Lyn and Src, Akt, and ERK1/2. In addition, sophoraflavanone G inhibited STAT5 phosphorylation in murine-bone-marrow-derived pro-B cells transfected with translocated Ets Leukemia (TEL)-JAKs and cytokine-induced rat pre-T lymphoma cells, as well as STAT5b reporter activity in TEL-JAKs and STAT5b reporter systems. Sophoraflavanone G also inhibited nuclear factor-κB (NF-κB) signaling in multiple myeloma cells. Furthermore, sophoraflavanone G inhibited cancer cell proliferation and induced apoptosis by regulating the expression of apoptotic and anti-apoptotic proteins. Our data suggest that sophoraflavanone G is a novel small-molecule inhibitor of STAT signaling by targeting upstream signals of STATs that may have therapeutic potential for cancers caused by persistently activated STAT proteins.
authors: Department of Pharmacology and Biomedical Science, Seoul National University College of Medicine, Seoul, Republic of Korea; Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Byung-Hak
authors: BH
authors: Kim
authors: Cheolhee
authors: C
authors: Won
authors: Yun-Han
authors: YH
authors: Lee
authors: Jung Sook
authors: JS
authors: Choi
authors: Kum Hee
authors: KH
authors: Noh
authors: Songhee
authors: S
authors: Han
authors: Haeri
authors: H
authors: Lee
authors: Chang Seok
authors: CS
authors: Lee
authors: Dong-Sup
authors: DS
authors: Lee
authors: Sang-Kyu
authors: SK
authors: Ye
authors: Myoung-Hwan
authors: MH
authors: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D044950:Flavanones; D016328:NF-kappa B; D050791:STAT Transcription Factors; D014443:Tyrosine; C064849:vexibinol
keywords: Apoptosis; Cancer; STATs; Small-molecule inhibitor; Sophoraflavanone G