Apigenin inhibits proliferation and invasion, and induces apoptosis and cell cycle arrest in human melanoma cells

Oncol Rep. 2017 Apr;37(4):2277-2285. doi: 10.3892/or.2017.5450. Epub 2017 Feb 14.


Malignant melanoma is the most invasive and fatal form of cutaneous cancer. Moreover it is extremely resistant to conventional chemotherapy and radiotherapy. Apigenin, a non-mutagenic flavonoid, has been found to exhibit chemopreventive and/or anticancerogenic properties in many different types of human cancer cells. Therefore, apigenin may have particular relevance for development as a chemotherapeutic agent for cancer treatment. In the present study, we investigated the effects of apigenin on the viability, migration and invasion potential, dendrite morphology, cell cycle distribution, apoptosis, phosphorylation of the extracellular signal-regulated protein kinase (ERK) and the AKT/mTOR signaling pathway in human melanoma A375 and C8161 cell lines in vitro. Apigenin effectively suppressed the proliferation of melanoma cells in vitro. Moreover, it inhibited cell migration and invasion, lengthened the dendrites, and induced G2/M phase arrest and apoptosis. Furthermore, apigenin promoted the activation of cleaved caspase-3 and cleaved PARP proteins and decreased the expression of phosphorylated (p)‑ERK1/2 proteins, p-AKT and p-mTOR. Consequently, apigenin is a novel therapeutic candidate for melanoma.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apigenin / pharmacology*
  • Apoptosis
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Melanoma / drug therapy
  • Melanoma / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*


  • Antineoplastic Agents, Phytogenic
  • Apigenin
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt