Water-extracted branch of Cinnamomum cassia promotes lung cancer cell apoptosis by inhibiting pyruvate dehydrogenase kinase activity

J Pharmacol Sci. 2018 Oct;138(2):146-154. doi: 10.1016/j.jphs.2018.10.005. Epub 2018 Oct 18.

Abstract

Cinnamomum cassia Blume has been widely reported as the anti-tumor agent. However, the precise mechanism underlying its pro-apoptotic action is still not clear. Restraining aerobic glycolysis through suppression of pyruvate dehydrogenase kinase (PDHK) is a promising strategy for cancer inhibition. In this study, we performed to investigate the anti-tumor action of C. cassia is mediated by PDHK inhibition. The inhibition of water-extracted branch of C. cassia (WBCC) on the activity of PDHK using both in vitro and cell-based kinase assay were examined in several lung cancer cells. WBCC reduced viabilities of several lung cancer cells with minimal cytotoxicity on normal bronchial epithelial cells. WBCC decreased lactate production through inhibiting activity of PDHK. In consequence of PDHK inhibition, WBCC increased ROS production, which damage mitochondria membrane stability. In addition, WBCC induced ROS- and mitochondria-dependent apoptotic cell death. Among the components of WBCC, cinnamic acid was founded as a major inhibitor on PDHK activity. This is first report that WBCC induces apoptosis of lung cancer cells through inhibiting PDHK activity. Our findings suggest that WBCC and cinnamic acid can be potential candidates for developing novel anti-cancer drugs through glycolysis metabolism.

Keywords: Aerobic glycolysis; Apoptosis; Cinnamic acid; Cinnamomum cassia; Pyruvate dehydrogenase kinase.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cells, Cultured
  • Cinnamomum aromaticum / chemistry*
  • Glycolysis / drug effects
  • Humans
  • Lactates / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Plant Extracts / pharmacology*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Stimulation, Chemical
  • Tumor Cells, Cultured
  • Water*

Substances

  • Antineoplastic Agents, Phytogenic
  • Lactates
  • Plant Extracts
  • Pyruvate Dehydrogenase Acetyl-Transferring Kinase
  • Water
  • Protein-Serine-Threonine Kinases