Glutaminase 1 inhibition reduces thymidine synthesis in NSCLC

Jae Seon Lee, Joon H. Kang, Seon Hyeong Lee, Chang Hun Lee, Jaekyoung Son, Soo Youl Kim

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

We found that non-small cell lung cancer (NSCLC) is remarkably sensitive to the regulation of glutamine supply by testing the metabolic dependency of 11 cancer cell lines against regulation of glycolysis, autophagy, fatty acid synthesis, and glutamine supply. Glutamine is known as a key supplement of cancer cell growth that is converted to α-ketoglutarate for anabolic biogenesis via glutamate by glutaminase 1 (GLS1). GLS1 inhibition using 10 μM of bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) showed about 50% cell growth arrest by SRB assay. By testing the synergistic effects of conventional therapeutics, BPTES combined with 5-fluorouracil (5-FU), an irreversible inhibitor of thymidylate synthase, significant effects were observed on cell growth arrest in NSCLC. We found that GLS1 inhibition using BPTES reduced metabolic intermediates including thymidine and carbamoyl phosphate. Reduction of thymidine and carbamoyl-phosphate synthesis by BPTES treatment exacerbated pyrimidine supply by combination with 5-FU, which induced cell death synergistically in NSCLC.

Original languageEnglish
Pages (from-to)374-382
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume477
Issue number3
DOIs
StatePublished - 26 Aug 2016

Keywords

  • 5-fluorouracil
  • Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide
  • Cancer metabolism
  • Glutaminase 1
  • Non-small cell lung cancer

Fingerprint

Dive into the research topics of 'Glutaminase 1 inhibition reduces thymidine synthesis in NSCLC'. Together they form a unique fingerprint.

Cite this