Reduction of invasion and cell stemness and induction of apoptotic cell death by Cinnamomum cassia extracts on human osteosarcoma cells

Environ Toxicol. 2022 Jun;37(6):1261-1274. doi: 10.1002/tox.23481. Epub 2022 Feb 11.

Abstract

Cinnamomum cassia possesses antioxidative activity and induces the apoptotic properties of various cancer types. However, its effect on osteosarcoma invasion and cancer stemness remains ambiguous. Here, we examined the molecular evidence of the anti-invasive effects of ethanoic C. cassia extracts (CCE). Invasion and migration were obviously suppressed after the expression of urokinase-type plasminogen activator and matrix metalloprotein 2 in human osteosarcoma 143B cells were downregulated. CCE reversed epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor β1 and downregulated mesenchymal markers, such as snail-1 and RhoA. CCE suppressed self-renewal property and the expression of stemness genes (aldehyde dehydrogenase, Nanog, and CD44) in the 143B cells. CCE suppressed cell viability, reduced the colony formation of osteosarcoma cancer cells, and induced apoptotic cell death in the 143B cells, as indicated by caspase-9 activation. The xenograft tumor model of immunodeficient BALB/c nude mice showed that CCE administered in vivo through oral gavage inhibited the growth of implanted 143B cells. These findings indicated that CCE inhibited the invasion, migration, and cancer stemness of the 143B cells. CCE reduced proliferation of 143B cell possibly because of the activation of caspase-9 and the consequent apoptosis, suggesting that CCE is a potential anticancer supplement for osteosarcoma.

Keywords: Cinnamomum cassia; apoptosis; epithelial-to-mesenchymal transition; invasion; stemness.

MeSH terms

  • Animals
  • Apoptosis
  • Bone Neoplasms* / pathology
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cinnamomum aromaticum*
  • Epithelial-Mesenchymal Transition
  • Humans
  • Mice
  • Mice, Nude
  • Osteosarcoma* / pathology
  • Plant Extracts / pharmacology

Substances

  • Plant Extracts
  • Caspase 9