title: Silibinin and STAT3: A natural way of targeting transcription factors for cancer therapy.
abstract: Signal transducer and activator of transcription 3 (STAT3) is constitutively activated in many different types of cancer and plays a pivotal role in tumor growth and metastasis. Retrospective studies have established that STAT3 expression or phospho-STAT3 (pSTAT3 or activated STAT3) are poor prognostic markers for breast, colon, prostate and non-small cell lung cancer. Silibinin or silybin is a natural polyphenolic flavonoid which is present in seed extracts of milk thistle (Silybum marianum). Silibinin has been shown to inhibit multiple cancer cell signaling pathways in preclinical models, demonstrating promising anticancer effects in vitro and in vivo. This review summarizes evidence suggesting that silibinin can inhibit pSTAT3 in preclinical cancer models. We also discuss current strategies to overcome the limitations of oral administration of silibinin to cancer patients to translate the bench results to the bed side. Finally, we review the ongoing clinical trials exploring the role of silibinin in cancer.
authors.affiliation: Medical Oncology, Catalan Institute of Oncology, Girona, Catalonia, Spain; Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain. Electronic address: jbosch@iconcologia.net.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bosch-Barrera
authors.affiliation: Girona Biomedical Research Institute (IDIBGI), Girona, Catalonia, Spain; Metabolism & Cancer Group, Translational Research Laboratory, Catalan Institute of Oncology, Girona, Catalonia, Spain.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menendez
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D000077385:Silybin; D012838:Silymarin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D050796:STAT3 Transcription Factor; D012838:Silymarin; D000077385:Silybin
keywords: Cancer; Legasil®; STAT3; Silibinin; Siliphos; Silybin; Silymarin