Eriocitrin from lemon suppresses the proliferation of human hepatocellular carcinoma cells through inducing apoptosis and arresting cell cycle

Cancer Chemother Pharmacol. 2016 Dec;78(6):1143-1150. doi: 10.1007/s00280-016-3171-y. Epub 2016 Oct 20.

Abstract

Hepatocellular carcinoma is a lethal cancer with high recurrence ratio and lacks effective therapeutics. In the past few years, it has been reported that increased intake of vegetables and fruits could reduce the cancer incidence, which suggests dietary agents might possess anticancer effects. Eriocitrin is a flavonoid isolated from lemon, which is known as a strong antioxidant agent. We here for the first time demonstrated that eriocitrin could inhibit the proliferation of hepatocellular carcinoma cell lines by arresting cell cycle in S phase through up-regulation of p53, cyclin A, cyclin D3 and CDK6. Furthermore, we found that eriocitrin could trigger apoptosis by activating mitochondria-involved intrinsic signaling pathway. Thus, eriocitrin might be regarded as a potential chemopreventive natural product to inhibit the early malignant transformation of hepatocellular carcinoma.

Keywords: Apoptosis; Cell cycle arrest; Eriocitrin; Hepatocellular carcinoma.

MeSH terms

  • Activating Transcription Factor 1 / metabolism
  • Apoptosis / drug effects*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Caspases / physiology
  • Cell Cycle Checkpoints / drug effects*
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / drug effects
  • Citrus / chemistry
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Flavanones / pharmacology*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • MAP Kinase Signaling System / drug effects
  • Phosphorylation

Substances

  • ATF1 protein, human
  • Activating Transcription Factor 1
  • CREB1 protein, human
  • Cyclic AMP Response Element-Binding Protein
  • Flavanones
  • eriocitrin
  • Caspases