Hyperforin Inhibits Cell Growth by Inducing Intrinsic and Extrinsic Apoptotic Pathways in Hepatocellular Carcinoma Cells

Anticancer Res. 2017 Jan;37(1):161-167. doi: 10.21873/anticanres.11301.

Abstract

The aim of the present study was to investigate the antitumor effect and mechanism of action of hyperforin in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro. Cells were treated with different concentrations of hyperforin for different periods of time. Effects of hyperforin on cell viability, apoptosis signaling, and expression of anti-apoptotic and proliferative proteins [cellular FLICE-like inhibitory protein (c-FLIP), X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia 1(MCL1), and cyclin-D1] were investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, and western blotting. Hyperforin significantly inhibited cell viability and expression of anti-apoptotic and proliferative proteins. We also found that hyperforin significantly induced accumulation of cells in sub-G1 phase, loss of mitochondrial membrane potential, and increased levels of active caspase-3, and caspase-8. Taken together, our findings indicate that hyperforin triggers inhibition of tumor cell growth by inducing intrinsic and extrinsic apoptotic pathways in HCC SK-Hep1 cells.

Keywords: Hepatocellular carcinoma; apoptosis; hyperforin.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • G1 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Membrane Potential, Mitochondrial / drug effects
  • Phloroglucinol / analogs & derivatives*
  • Phloroglucinol / pharmacology
  • Signal Transduction / drug effects*
  • Terpenes / pharmacology*
  • Time Factors

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • Terpenes
  • Phloroglucinol
  • hyperforin