دورية أكاديمية
أعرض في EDS

Pharmacological inhibition of tumor anabolism and host catabolism as a cancer therapy

التفاصيل البيبلوغرافية
العنوان: Pharmacological inhibition of tumor anabolism and host catabolism as a cancer therapy
المؤلفون: Alejandro Schcolnik-Cabrera, Alma Chavez-Blanco, Guadalupe Dominguez-Gomez, Mandy Juarez, Ariana Vargas-Castillo, Rafael Isaac Ponce-Toledo, Donna Lai, Sheng Hua, Armando R. Tovar, Nimbe Torres, Delia Perez-Montiel, Jose Diaz-Chavez, Alfonso Duenas-Gonzalez
المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
بيانات النشر: Nature Portfolio, 2021.
سنة النشر: 2021
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract The malignant energetic demands are satisfied through glycolysis, glutaminolysis and de novo synthesis of fatty acids, while the host curses with a state of catabolism and systemic inflammation. The concurrent inhibition of both, tumor anabolism and host catabolism, and their effect upon tumor growth and whole animal metabolism, have not been evaluated. We aimed to evaluate in colon cancer cells a combination of six agents directed to block the tumor anabolism (orlistat + lonidamine + DON) and the host catabolism (growth hormone + insulin + indomethacin). Treatment reduced cellular viability, clonogenic capacity and cell cycle progression. These effects were associated with decreased glycolysis and oxidative phosphorylation, leading to a quiescent energetic phenotype, and with an aberrant transcriptomic landscape showing dysregulation in multiple metabolic pathways. The in vivo evaluation revealed a significant tumor volume inhibition, without damage to normal tissues. The six-drug combination preserved lean tissue and decreased fat loss, while the energy expenditure got decreased. Finally, a reduction in gene expression associated with thermogenesis was observed. Our findings demonstrate that the simultaneous use of this six-drug combination has anticancer effects by inducing a quiescent energetic phenotype of cultured cancer cells. Besides, the treatment is well-tolerated in mice and reduces whole animal energetic expenditure and fat loss.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-021-84538-6
URL الوصول: https://doaj.org/article/f99339e0268a4075931c6a4545b04390
رقم الأكسشن: edsdoj.f99339e0268a4075931c6a4545b04390
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-021-84538-6