Cinnamon bark extract suppresses metastatic dissemination of cancer cells through inhibition of glycolytic metabolism

Joji Nakayama, Yuki Konno, Ami Maruyama, Masaru Tomita, Hideki Makinoshima

Research output: Contribution to journalArticlepeer-review

Abstract

Metastasis is responsible for approximately 90% of cancer-associated mortality and proceeds through multiple steps. Several herbal medicines are reported to inhibit primary tumor growth, but the suppressor effects of the medicines on metastasis progression are still not fully elucidated. Here we report that cinnamon bark extract (CBE) has a suppressor effect on metastatic dissemination of cancer cells. Through a phenotypic screening using zebrafish embryos, CBE was identified to interfere with the gastrulation progression of zebrafish embryos, of which the molecular mechanisms are conserved in metastasis progression. A Boyden chamber assay showed that CBE decreased cell motility and invasion of MDA-MB-231 human breast cancer cells without affecting their cell viability. Furthermore, CBE suppressed metastatic dissemination of the cells in a zebrafish xenotransplantation model. Quantitative metabolome analyses revealed that the productions of glucose-6-phosphate (G6P) and fructose 6-phosphate which are intermediate metabolites of glycolytic metabolism were interrupted in CBE-treated cells. qPCR and western-blotting analyses revealed that CBE-treated cells showed decreased expression of hexokinase 2 (HK2) which yields G6P. Pharmacological inhibition of HK2 with 2-deoxy-D-glucose suppressed cell invasion and migration of the cells without affecting their cell viability. Taken together, CBE suppresses metastatic dissemination of cancer cells through inhibition of glycolysis metabolism.

Original languageEnglish
Pages (from-to)686-692
Number of pages7
JournalJournal of Natural Medicines
Volume76
Issue number3
DOIs
Publication statusPublished - 2022 Jun

Keywords

  • Cinnamon bark
  • Glycolysis metabolism
  • Metastasis
  • Phenotyping screening
  • Zebrafish

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

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