Impact of sodium dichloroacetate alone and in combination therapies on lung tumor growth and metastasis

Aya Al-Azawi, Shahrazad Sulaiman, Kholoud Arafat, Javed Yasin, Abderrahim Nemmar, Samir Attoub

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Metabolic reprogramming has been recognized as an essential emerging cancer hallmark. Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been reported to have anti-cancer effects by reversing tumor-associated glycolysis. This study was performed to explore the anti-cancer potential of DCA in lung cancer alone and in combination with chemo-and targeted therapies using two non-small cell lung cancer (NSCLC) cell lines, namely, A549 and LNM35. DCA markedly caused a concentration-and time-dependent decrease in the viability and colony growth of A549 and LNM35 cells in vitro. DCA also reduced the growth of tumor xenografts in both a chick embryo chorioallantoic membrane and nude mice models in vivo. Furthermore, DCA decreased the angiogenic capacity of human umbilical vein endothelial cells in vitro. On the other hand, DCA did not inhibit the in vitro cellular migration and invasion and the in vivo incidence and growth of axillary lymph nodes metastases in nude mice. Treatment with DCA did not show any toxicity in chick embryos and nude mice. Finally, we demonstrated that DCA significantly enhanced the anti-cancer effect of cisplatin in LNM35. In addition, the combination of DCA with gefitinib or erlotinib leads to additive effects on the inhibition of LNM35 colony growth after seven days of treatment and to synergistic effects on the inhibition of A549 colony growth after 14 days of treatment. Collectively, this study demonstrates that DCA is a safe and promising therapeutic agent for lung cancer.

Original languageEnglish
Article number12553
JournalInternational journal of molecular sciences
Volume22
Issue number22
DOIs
Publication statusPublished - Nov 1 2021

Keywords

  • Angiogenesis
  • Dichloroacetate
  • Erlotinib
  • Gefitinib
  • Lung cancer
  • Pyruvate dehydrogenase kinase inhibitor
  • Tumor growth

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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