β-Asarone suppresses Wnt/β-catenin signaling to reduce viability, inhibit migration/invasion/adhesion and induce mitochondria-related apoptosis in lung cancer cells

Biomed Pharmacother. 2018 Oct;106:821-830. doi: 10.1016/j.biopha.2018.07.009. Epub 2018 Jul 11.

Abstract

Lung cancer is the leading cause of cancer death worldwide. Chemotherapy is one of the most effective strategies for lung cancer treatment. However, the side effects of chemotherapy limit the application of chemotherapeutic agents. The β-Asarone, a low-toxicity natural compound from a traditional Chinese medicinal herb, has been demonstrated to display anticancer activities in multiple cancer types. However, the anticancer activities of β-Asarone in lung cancer have not been shown, and the underlying molecular mechanisms are still unclear. In the current study, we show that β-Asarone displays a dose-dependent inhibitory effect on the viability of lung cancer cells. Additionally, β-Asarone significantly suppresses the cell migration, invasion, and adhesion of lung cancer cells. Moreover, β-Asarone induces apoptosis associated with the activation of caspase-9 and caspase-3, the upregulation of XAF1, Puma, Bax (Ser184) and Bad (Ser112), the downregulation of XIAP, Bcl-2 and Survivin, the translocation of Bax, Bad, phospho-Bax (Ser184), phospho-Bad (Ser112) and cytochrome C and the reduction of the mitochondrial membrane potential. Mechanistically, our study shows that β-Asarone inhibits Wnt/β-catenin signaling. Rescuing the activation of Wnt/β-catenin signaling overcomes β-Asarone-induced anticancer effects. Taken together, our data provide the first evidence of the anticancer effects of β-Asarone in lung cancer, demonstrates that the inhibition of Wnt/β-catenin signaling could be critical for β-Asarone-induced anticancer effects. Our study thus suggests a potential application of β-Asarone as an anticancer agent in the clinical treatment of lung cancer.

Keywords: Apoptosis; Cell viability; Lung cancer; Migration/invasion/adhesion; Mitochondrial; Natural compounds; β-Asarone.

MeSH terms

  • Anisoles / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Adhesion / drug effects*
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Neoplasm Invasiveness
  • Time Factors
  • Wnt Signaling Pathway / drug effects*

Substances

  • Anisoles
  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • asarone