Anticancer effects of methanol extract of Myrmecodia platytyrea Becc. leaves against human hepatocellular carcinoma cells via inhibition of ERK and STAT3 signaling pathways

Int J Oncol. 2018 Jan;52(1):201-210. doi: 10.3892/ijo.2017.4178. Epub 2017 Oct 24.

Abstract

Myrmecodia platytyrea Becc., a member of the Rubiaceae family, is found throughout Southeast Asia and has been traditionally used to treat cancer. However, there is limited pharmacological information on this plant. We investigated the anticancer effects of the methanol extract of Myrmecodia platytyrea Becc. leaves (MMPL) and determined the molecular mechanisms underlying the effects of MMPL on metastasis in human hepatocellular carcinoma (HCC) cells. MMPL dose-dependently inhibited cell migration and invasion in SK‑Hep1 and Huh7 cells. In addition, MMPL strongly suppressed the enzymatic activity of matrix metalloproteinases (MMP‑2 and MMP‑9). Diminished telomerase activity by MMPL resulted in the suppression of both telomerase activity and telomerase-associated gene expression. The levels of urokinase-type plasminogen activator receptor (uPAR) expression as well as the phosphorylation levels of signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (ERK) were also attenuated by MMPL. The above results collectively suggest that MMPL has anticancer effects in HCC and that MMPL can serve as an effective therapeutic agent for treating human liver cancer.

MeSH terms

  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • MAP Kinase Signaling System / drug effects*
  • Magnoliopsida / chemistry*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinase Inhibitors / isolation & purification
  • Matrix Metalloproteinase Inhibitors / pharmacology
  • Methanol / chemistry
  • Neoplasm Invasiveness
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism

Substances

  • Matrix Metalloproteinase Inhibitors
  • Plant Extracts
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Extracellular Signal-Regulated MAP Kinases
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Methanol