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- Title
The inhibition of c-MYC transcription factor modulates the expression of glycolytic and glutaminolytic enzymes in FaDu hypopharyngeal carcinoma cells.
- Authors
Kleszcz, Robert; Paluszczak, Jarosław; Krajka-Kuźniak, Violetta; Baer-Dubowska, Wanda
- Abstract
Background. Cancer cells are dependent on aerobic glycolysis for energy production and increased glutamine consumption. HIF-1α and c-MYC transcription factors regulate the expression of glycolytic and glutaminolytic genes. Their activity may be repressed by SIRT6. Head and neck carcinomas show frequent activation of c-MYC function and SIRT6 down-regulation, which contributes to a strong dependence on glucose and glutamine availability. Objectives. The aim of this study was to compare the influence of HIF-1α and c-MYC inhibitors (KG-548 and 10058-F4, respectively) and potential SIRT6 inducers - resveratrol and its synthetic derivative DMU-212 with the effect of glycolysis and glutaminolysis inhibitors (2-deoxyglucose and aminooxyacetic acid, respectively) on the metabolism and expression of metabolic enzymes in FaDu hypopharyngeal carcinoma cells. Material and methods. Cell viability was assessed by means of an MTT assay. Quantitative PCR was performed to evaluate the expression of SIRT6, HIF-1α, c-MYC, GLUT1, SLC1A5, HK2, PFKM, PKM2, LDHA, GLS, and GDH. The release of glycolysis and glutaminolysis end-products into the culture medium - lactate and ammonia, respectively - was assessed using standard colorimetric assays. Results. Lactate production was significantly inhibited by 10058-F4, KG-548, and 2-deoxyglucose. Moreover, 10058-F4 strongly reduced the amount of ammonia release. The effects of 10058-F4 activity can be attributed to a reduction in the expression of PKM2 and LDHA. On the other hand, the induction of SIRT6 expression by resveratrol and DMU-212 was not associated with significant modulation of the expression of metabolic enzymes. Conclusions. Overall, the results of this study indicate that the inhibition of c-MYC may be considered to be a promising strategy of the modulation of cancer-related metabolic changes in head and neck carcinomas.
- Subjects
CANCER cells; GLYCOLYSIS; GENE expression; HEAD &; neck cancer; CELL proliferation
- Publication
Advances in Clinical & Experimental Medicine, 2018, Vol 27, Issue 6, p735
- ISSN
1899-5276
- Publication type
Article
- DOI
10.17219/acem/68979