Foeniculum vulgare seed extract induces apoptosis in lung cancer cells partly through the down-regulation of Bcl-2

Biomed Pharmacother. 2021 Mar;135:111213. doi: 10.1016/j.biopha.2020.111213. Epub 2021 Jan 1.


The factors behind the pathogenesis of lung cancer are not clear, and treatment failure is generally caused by drug resistance, recurrence, and metastasis. Development of new therapeutic agents to overcome drug-resistance remains a challenge clinically. Various extracts of Foeniculum vulgare have shown promising anticancer activity; however, effects on lung cancer and the underlying molecular mechanisms of action are not clear. In the present study, we found that the ethanol extract of Foeniculum vulgare seeds (EEFS) significantly reduced lung cancer cell growth in vitro and in vivo. EEFS decreased the viability of and triggered apoptosis in the lung cancer cell lines NCI-H446 and NCI-H661. EEFS induced apoptosis mainly through inhibition of Bcl-2 protein expression, reduction of mitochondrial membrane potential, and release of Cytochrome C. Moreover, EEFS significantly inhibited colony formation and cell migration in lung cancer cells. EEFS also effectively inhibited the growth of xenograft tumors derived from NCI-446 cells by reducing Bcl-2 protein expression and inducing apoptosis. Taken together, these findings suggest that EEFS exerts anti-lung cancer activity by targeting the Bcl-2 protein and may have potential as a therapeutic drug for lung cancer.

Keywords: Apoptosis; Bcl-2; Chemotherapy; Foeniculum vulgare; Lung cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Foeniculum* / chemistry
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Seeds
  • Signal Transduction
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents, Phytogenic
  • BCL2 protein, human
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2