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Lung Cancer Management with Silibinin: A Historical and Translational Perspective

Girona Biomedical Research Institute (IDIBGI), 17190 Girona, Spain
Metabolism and Cancer Group, Program against Cancer Therapeutic Resistance (ProCURE), Catalan Institute of Oncology, 17007 Girona, Spain
Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche (IDiBE) and Instituto de Biología Molecular y Celular (IBMC), Universidad Miguel Hernández (UMH), 03202 Elche, Spain
Unitat de Recerca Biomèdica (URB-CRB), Hospital Universitari de Sant Joan, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, 43201 Reus, Spain
Medical Oncology, Catalan Institute of Oncology, Dr. Josep Trueta Hospital of Girona, 17007 Girona, Spain
Department of Medical Sciences, Faculty of Medicine, University of Girona (UdG), 17003 Girona, Spain
Authors to whom correspondence should be addressed.
Both authors contributed equally to this work.
Academic Editor: Thomas Efferth
Pharmaceuticals 2021, 14(6), 559;
Received: 12 May 2021 / Revised: 31 May 2021 / Accepted: 9 June 2021 / Published: 11 June 2021
The flavonolignan silibinin, the major bioactive component of the silymarin extract of Silybum marianum (milk thistle) seeds, is gaining traction as a novel anti-cancer therapeutic. Here, we review the historical developments that have laid the groundwork for the evaluation of silibinin as a chemopreventive and therapeutic agent in human lung cancer, including translational insights into its mechanism of action to control the aggressive behavior of lung carcinoma subtypes prone to metastasis. First, we summarize the evidence from chemically induced primary lung tumors supporting a role for silibinin in lung cancer prevention. Second, we reassess the preclinical and clinical evidence on the effectiveness of silibinin against drug resistance and brain metastasis traits of lung carcinomas. Third, we revisit the transcription factor STAT3 as a central tumor-cell intrinsic and microenvironmental target of silibinin in primary lung tumors and brain metastasis. Finally, by unraveling the selective vulnerability of silibinin-treated tumor cells to drugs using CRISPR-based chemosensitivity screenings (e.g., the hexosamine biosynthesis pathway inhibitor azaserine), we illustrate how the therapeutic use of silibinin against targetable weaknesses might be capitalized in specific lung cancer subtypes (e.g., KRAS/STK11 co-mutant tumors). Forthcoming studies should take up the challenge of developing silibinin and/or next-generation silibinin derivatives as novel lung cancer-preventive and therapeutic biomolecules. View Full-Text
Keywords: silibinin; silymarin; non-small cell lung cancer; EMT; metastasis; STAT3 silibinin; silymarin; non-small cell lung cancer; EMT; metastasis; STAT3
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MDPI and ACS Style

Verdura, S.; Cuyàs, E.; Ruiz-Torres, V.; Micol, V.; Joven, J.; Bosch-Barrera, J.; Menendez, J.A. Lung Cancer Management with Silibinin: A Historical and Translational Perspective. Pharmaceuticals 2021, 14, 559.

AMA Style

Verdura S, Cuyàs E, Ruiz-Torres V, Micol V, Joven J, Bosch-Barrera J, Menendez JA. Lung Cancer Management with Silibinin: A Historical and Translational Perspective. Pharmaceuticals. 2021; 14(6):559.

Chicago/Turabian Style

Verdura, Sara, Elisabet Cuyàs, Verónica Ruiz-Torres, Vicente Micol, Jorge Joven, Joaquim Bosch-Barrera, and Javier A. Menendez 2021. "Lung Cancer Management with Silibinin: A Historical and Translational Perspective" Pharmaceuticals 14, no. 6: 559.

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