| Autor: |
Khalifa, Amr, Guijarro, Ana, Ravera, Silvia, Bertola, Nadia, Adorni, Maria Pia, Papotti, Bianca, Raffaghello, Lizzia, Benelli, Roberto, Becherini, Pamela, Namatalla, Asmaa, Verzola, Daniela, Reverberi, Daniele, Monacelli, Fiammetta, Cea, Michele, Pisciotta, Livia, Bernini, Franco, Caffa, Irene, Nencioni, Alessio |
| Předmět: |
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| Zdroj: |
Nature Communications; 11/22/2023, Vol. 14 Issue 1, p1-16, 16p |
| Abstrakt: |
Identifying oncological applications for drugs that are already approved for other medical indications is considered a possible solution for the increasing costs of cancer treatment. Under the hypothesis that nutritional stress through fasting might enhance the antitumour properties of at least some non-oncological agents, by screening drug libraries, we find that cholesterol biosynthesis inhibitors (CBIs), including simvastatin, have increased activity against cancers of different histology under fasting conditions. We show fasting's ability to increase CBIs' antitumour effects to depend on the reduction in circulating insulin, insulin-like growth factor-1 and leptin, which blunts the expression of enzymes from the cholesterol biosynthesis pathway and enhances cholesterol efflux from cancer cells. Ultimately, low cholesterol levels through combined fasting and CBIs reduce AKT and STAT3 activity, oxidative phosphorylation and energy stores in the tumour. Our results support further studies of CBIs in combination with fasting-based dietary regimens in cancer treatment and highlight the value of fasting for drug repurposing in oncology. Nutritional stress induced by short-term dietary restriction has been shown to alter the activity of some anti-tumour drugs. Here, the authors demonstrate that periodic fasting enhances the anti-tumour effect of cholesterol biosynthesis inhibitors via decreased AKT-STAT3 signaling and oxidative phosphorylation. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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