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Glutamine antagonist with diet deficient in glutamine and aspartate reduce tumor growth
K Yoshioka1, H Takehara, A Okada
11st Department of Surgery, School of Medicine, University of Tokushima, Japan.
Abstract:
This study was designed to investigate whether a combination of a glutamine antagonist (DON) and a diet deficient in glutamate and aspartate (AG) altered glutamine metabolism in tumor tissue, and inhibited tumor growth. In experiment-1, 21 male Donryu rats were fed with AG and implanted with Yoshida's Sarcoma. Of them, 7 rats were sacrificed on the 5th day (group AG), other 7 were sacrificed next day (group AG-1) and the remaining 7 were injected with DON on the 5th day and sacrificed next day (group AG+D). The tumor weight of group AG+D was significantly lower than of group AG, or of group AG-1. In experiment-2, of 23 rats, 9 were fed with control diet and 14 were fed with AG and implanted. 12 were sacrificed on the 5th day (group C, AG), and 11 were injected with DON on the 5th day and sacrificed next day (group C+D, AG+D). The reduced ratio of tumor weight in group C+D and group AG+D were 25% and 67%, respectively. These results show that the tumor growth could be inhibited by using metabolic antagonist of glutamine, and that it had synergistic effect in conjunction with the imbalanced diet.
Insights
This study explored how a glutamine antagonist (DON) combined with a glutamate-aspartate deficient diet (AG) impacts tumor growth. The combination significantly inhibited tumor growth in rats, suggesting a synergistic effect for cancer therapy.
Area of Science:
- Biochemistry
- Oncology
- Metabolic Research
Background:
- Tumor cells often rely on glutamine metabolism for energy and biosynthesis.
- Targeting glutamine metabolism is a potential strategy for cancer treatment.
Purpose of the Study:
- To investigate the effects of a glutamine antagonist (DON) and an amino acid-deficient diet (AG) on glutamine metabolism and tumor growth.
- To determine if combining DON and AG has a synergistic effect on inhibiting tumor growth.
Main Methods:
- Rats with Yoshida's Sarcoma were divided into groups receiving either a control diet, an AG diet, or an AG diet with DON administration.
- Tumor weight was measured after specific treatment periods to assess growth inhibition.
Main Results:
- The combination of DON and the AG diet significantly reduced tumor weight compared to control or AG diet alone.
- Tumor weight reduction was 25% in the control diet + DON group and 67% in the AG diet + DON group.
Conclusions:
- Metabolic antagonism of glutamine, particularly with DON, can inhibit tumor growth.
- The combination of a glutamine antagonist and an imbalanced amino acid diet exhibits a synergistic effect in suppressing tumor growth, offering a promising therapeutic approach.