A new study has found that an anti-cancer drug promotes weight loss in mice when given at lower doses, according to Science Daily.
The study findings, published Thursday in the journal PLOS Biology, provide a promising new candidate for treating obesity.
Jiang Wei Wu and colleagues at Northwest A&F University in Shaanxi, China, found that the anti-tumor drug camptothecin prompted weight loss by activating a natural hunger-suppressing pathway.
A hormone called growth differentiation factor 15 (GDF15) circulates in response to various stimuli, including stress. Previous studies have shown that an increased level of GDF15 causes a drop in body weight, while reduction leads to obesity.
The current study authors searched for drugs that could increase the production of GDF15. They found that cells exposed to a drug called camptothecin increased GDF15 expression.
Discovered in 1966 by M. E. Wall and M. C. Wani, camptothecin is a topoisomerase inhibitor, which is derived from the Asian tree Camptotheca acuminate. Topoisomerase is a nuclear enzyme that plays essential roles in DNA replication, transcription, chromosome segregation, and recombination. So, camptothecin is an inhibitor of a DNA repair enzyme, hence used as an anti-tumor drug.
The authors studied the effects of camptothecin in obese mice and found that the drug rapidly elevated the levels of GDF15 in the blood. Over the course of 30 days, the researchers found a reduced food intake by about 12% and body weight by about 11%.
Scientists were studying the anti-tumor effects of camptothecin, but they had to keep the trials aside due to safety concerns. The drug’s safety as an anti-obesity drug has yet to be determined, according to Wu.
However, Wu said that the dose used in the current study was about one-thirtieth of the lowest dose used in human trials.
Wu said, “We believe our results convincingly argue that camptothecin may have therapeutic benefits for obesity and its associated metabolic disorders. Further study is needed to evaluate its efficacy and safety in advanced models to increase the translational impact.”
“In this study, by using in silico drug-screening approach, we discovered that Camptothecin (CPT), a previously identified anti-tumor drug by the US National Cancer Institute, is a GDF15 inducer,” Wu added. “CPT elevates circulating GDF15 via activation of hepatic ISR pathway, this activates the GDF15 receptor GFRAL in the hindbrain AP, which subsequently suppresses food intake and reduces body weight in obese mice.”
