Author, as appears in the article.: Verdura, Sara; Cuyas, Elisabet; Ruiz-Torres, Veronica; Micol, Vicente; Joven, Jorge; Bosch-Barrera, Joaquim; Menendez, Javier A.;

Department: Medicina i Cirurgia

URV's Author/s: Joven Maried, Jorge

Keywords: Stat3 Silymarin Silibinin Sencar mouse skin Non-small cell lung cancer Multidrug-resistance Milk thistle Metastasis Lysyl oxidase Histone deacetylase Growth-inhibition Factor-kappa-b Epithelial-mesenchymal transition Emt Drug-resistance Acquired-resistance

Abstract: 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.

Thematic Areas: Saúde coletiva Química Pharmacology & pharmacy Pharmaceutical science Molecular medicine Medicina ii Interdisciplinar Farmacia Drug discovery Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Chemistry, medicinal Biotecnología Biodiversidade

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: jorge.joven@urv.cat

Author identifier: 0000-0003-2749-4541

Record's date: 2023-02-19

Journal volume: 14

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.mdpi.com/1424-8247/14/6/559

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Pharmaceuticals. 14 (6):

APA: Verdura, Sara; Cuyas, Elisabet; Ruiz-Torres, Veronica; Micol, Vicente; Joven, Jorge; Bosch-Barrera, Joaquim; Menendez, Javier A.; (2021). Lung Cancer Management with Silibinin: A Historical and Translational Perspective. Pharmaceuticals, 14(6), -. DOI: 10.3390/ph14060559

Article's DOI: 10.3390/ph14060559

Entity: Universitat Rovira i Virgili

Journal publication year: 2021

Publication Type: Journal Publications