PT  - JOURNAL ARTICLE
AU  - Yuki Konno
AU  - Ami Maruyama
AU  - Masaru Tomita
AU  - Hideki Makinoshima
AU  - Joji Nakayama
TI  - Cinnamon bark extract suppresses metastatic dissemination of cancer cells through inhibition of glycolytic metabolism
AID  - 10.1101/2021.03.25.437098
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.25.437098
4099  - http://biorxiv.org/content/early/2021/06/07/2021.03.25.437098.short
4100  - http://biorxiv.org/content/early/2021/06/07/2021.03.25.437098.full
AB  - Metastasis, a leading contributor to the morbidity of cancer patients, occurs through multiple steps. As each of these steps is promoted by different molecular mechanisms, blocking metastasis needs to target each of these steps. Here we report that cinnamon bark extract (CBE) has a suppressor effect on metastatic dissemination of cancer cells. Though a zebrafish embryo screen which utilizes conserved mechanisms between metastasis and zebrafish gastrulation for identifying anti-metastasis drugs, CBE was identified to interfere with gastrulation progression of zebrafish. A zebrafish xenotransplantation model of metastasis validated that CBE suppressed metastatic dissemination of human cancer cells (MDA-MB-231). Interestingly, quantitative metabolome analyses revealed that CBE-treated MDA-MB-231 cells disrupted the production of glucose 6-phosphate (G6P) and fructose 6-phosphate (F6P), which are intermediate metabolites of glycolytic metabolism. CBE decreased the expression of hexokinase 2 (HK2), which catalyzes G6P production, and pharmacological inhibition of HK2 suppressed cell invasion and migration of MDA-MB-231 cells. Taken together, CBE suppressed metastatic dissemination of human cancer cells by inhibiting glycolytic metabolism.Competing Interest StatementThe authors have declared no competing interest.