Anti-Cancer and Other Health-Promoting Effects of Silibinin and Silibinin Derivatives

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 10051

Special Issue Editors

1. Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, 17005 Girona, Spain
2. Catalan Institute of Oncology (ICO)-Girona Biomedical Research Institute (IDIBGI), 17190 Girona, Spain
Interests: cancer; metabolism; metformin; aging; drug development
Special Issues, Collections and Topics in MDPI journals
1. Medical Oncology, Catalan Institute of Oncology, 17007 Girona, Catalonia, Spain
2. Girona Biomedical Research Institute (IDIBGI), 17190 Girona, Catalonia, Spain
Interests: lung cancer; brain metastasis; bioactive compounds
Special Issues, Collections and Topics in MDPI journals
1. Program Against Cancer Therapeutic Resistance (ProCURE), Metabolism and Cancer Group, Catalan Institute of Oncology, 17005 Girona, Spain
2. Metabolism & Cancer Group, Girona Biomedical Research Institute (IDIBGI), 17190 Girona, Spain
Interests: cancer; metabolism; metformin; aging; drug development
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The flavonolignan silibinin (or silybin) is considered the major bioactive component of silymarin, an extract of Silybum marianum (milk thistle) seeds that was classified by the World Health Organization in the 1970s as an official medicine with health-promoting properties. The well-known hepatoprotective, anti-inflammatory, and anti-fibrotic effects of silibinin have supported the therapeutic use of silymarin for the treatment of liver illnesses such as alcoholic liver disease, nonalcoholic liver disease, drug-induced liver injury, cirrhosis, viral hepatitis, and mushroom poisoning over the last 50 years.

 

In the last decade, an ever-growing number of preclinical studies have illuminated the potential anti-cancer effects of silibinin. Silibinin has been shown to exert significant tumoricidal activity against cultured cancer cells and xenografts, to enhance the efficacy of other anti-cancer therapeutic agents, to reduce the toxicity of cancer treatments, and to prevent and overcome the emergence of cancer drug resistance. However, the achievement of a bona fide, clinically relevant anti-cancer activity of silibinin remains controversial in human trials. Thus, whereas no significant anti-tumor activity of silibinin has been reported in prostate cancer tissues, certain silibinin-containing formulations have been successfully applied to lung cancer patients with established brain metastases, providing highly significant survival advantages, low toxicity and reversible secondary effects, and compatibility with the standard-of-care.

 

To encompass the remarkable breadth of ongoing investigation on silibinin and cancer, research articles, review articles as well as short communications covering a wide range of topics related to the therapeutic application of silibinin as an anti-cancer treatment, including but not limited to molecular mechanisms, signaling pathways, metabolism, pre-clinical studies, drug formulations, analogues, drug combinations, immune response, and clinical trials are welcomed for inclusion in this Special Issue of Pharmaceuticals. Manuscripts reporting on the health-promoting effects and molecular bases of silibinin (or other components of silymarin and its derivatives) for aging-related chronic diseases such as obesity, type 2 diabetes, metabolic syndrome, chronic respiratory diseases, cardiovascular diseases, neurodegenerative diseases, as well as viral infections including SARS-CoV-2/COVID-19 will also be welcomed in the issue.

Dr. Javier A. Menendez
Dr. Joaquim Bosch-Barrera
Dr. Elisabet Cuyàs Navarro
Guest Editors

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Keywords

  • silibinin (or silybin)
  • Silymarin and Derivatives
  • Molecular mechanisms of action
  • Cellular mechanisms of action
  • Metabolism and bioavailability
  • Drug development
  • Analogs
  • Pre-clinical studies
  • Metastasis
  • Immune system
  • Clinical trials
  • Epidemiology
  • Obesity
  • Type 2 diabetes
  • Metabolic syndrome
  • Chronic respiratory diseases
  • Chronic obstructive pulmonary disease
  • Asthma
  • Pulmonary hypertension
  • Cardiovascular disease
  • Myocardial infarction
  • Hypertension
  • Neurogenerative diseases
  • Amyotrophic lateral sclerosis
  • Parkinson’s diseases
  • Alzheimer’s disease
  • Huntington’s disease
  • Viral infections
  • HIV
  • SARS-CoV2
  • COVID-19

Published Papers (2 papers)

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18 pages, 2154 KiB  
Review
Lung Cancer Management with Silibinin: A Historical and Translational Perspective
by Sara Verdura, Elisabet Cuyàs, Verónica Ruiz-Torres, Vicente Micol, Jorge Joven, Joaquim Bosch-Barrera and Javier A. Menendez
Pharmaceuticals 2021, 14(6), 559; https://doi.org/10.3390/ph14060559 - 11 Jun 2021
Cited by 14 | Viewed by 4522
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 [...] Read more.
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. Full article
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15 pages, 2882 KiB  
Perspective
Clinical Management of COVID-19 in Cancer Patients with the STAT3 Inhibitor Silibinin
by Joaquim Bosch-Barrera, Ariadna Roqué, Eduard Teixidor, Maria Carmen Carmona-Garcia, Aina Arbusà, Joan Brunet, Begoña Martin-Castillo, Elisabet Cuyàs, Sara Verdura and Javier A. Menendez
Pharmaceuticals 2022, 15(1), 19; https://doi.org/10.3390/ph15010019 - 24 Dec 2021
Cited by 2 | Viewed by 3948
Abstract
COVID-19 pathophysiology is caused by a cascade of respiratory and multiorgan failures arising, at least in part, from the SARS-CoV-2-driven dysregulation of the master transcriptional factor STAT3. Pharmacological correction of STAT3 over-stimulation, which is at the root of acute respiratory distress syndrome (ARDS) [...] Read more.
COVID-19 pathophysiology is caused by a cascade of respiratory and multiorgan failures arising, at least in part, from the SARS-CoV-2-driven dysregulation of the master transcriptional factor STAT3. Pharmacological correction of STAT3 over-stimulation, which is at the root of acute respiratory distress syndrome (ARDS) and coagulopathy/thrombosis events, should be considered for treatment of severe COVID-19. In this perspective, we first review the current body of knowledge on the role of STAT3 in the pathogenesis of severe COVID-19. We then exemplify the potential clinical value of treating COVID-19 disease with STAT3 inhibitors by presenting the outcomes of two hospitalized patients with active cancer and COVID-19 receiving oral Legalon®—a nutraceutical containing the naturally occurring STAT3 inhibitor silibinin. Both patients, which were recruited to the clinical trial SIL-COVID19 (EudraCT number: 2020-001794-77) had SARS-CoV-2 bilateral interstitial pneumonia and a high COVID-GRAM score, and showed systemic proinflammatory responses in terms of lymphocytopenia and hypoalbuminemia. Both patients were predicted to be at high risk of critical COVID-19 illness in terms of intensive care unit admission, invasive ventilation, or death. In addition to physician’s choice of best available therapy or supportive care, patients received 1050 mg/day Legalon® for 10 days without side-effects. Silibinin-treated cancer/COVID-19+ patients required only minimal oxygen support (2–4 L/min) during the episode, exhibited a sharp decline of the STAT3-regulated C-reactive protein, and demonstrated complete resolution of the pulmonary lesions. These findings might inspire future research to advance our knowledge and improve silibinin-based clinical interventions aimed to target STAT3-driven COVID-19 pathophysiology. Full article
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