New publication by Schcolnik-Cabrera et al. in Nature Scientific Reports co-authored by Rafae Ponce-Toledo:
"Pharmacological inhibition of tumor anabolism and host catabolism as a cancer therapy"
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.
Read the full paper here or download below.
Original paper:
Scientific Reports, DOI: 10.1038/s41598-021-84538-6
Pharmacological inhibition of tumor anabolism and host catabolism as a cancer therapy
Alejandro Schcolnik-Cabrera, Alma Chaves-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
Full article:
Pharmacological inhibition of tumor anabolism and host catabolism as a cancer therapy | Scientific Reports (nature.com)
