Polygonatum cyrtonema lectin induces murine fibrosarcoma L929 cell apoptosis and autophagy via blocking Ras-Raf and PI3K-Akt signaling pathways

Biochimie. 2010 Dec;92(12):1934-8. doi: 10.1016/j.biochi.2010.08.009. Epub 2010 Aug 14.

Abstract

Polygonatum cyrtonema lectin (PCL), a mannose/sialic acid-binding lectin, has been reported to display remarkable anti-proliferative and apoptosis-inducing activities toward a variety of cancer cells; however, the precise molecular mechanisms by which PCL induces cancer cell death are still elusive. In the current study, we found that PCL could induce apoptosis and autophagy in murine fibrosarcoma L929 cells. Subsequently, we demonstrated that inhibition of Ras could promote L929 cell death, suggesting that Ras-Raf signaling pathway plays the key negative regulator in PCL-induced apoptosis. And, we showed that Ras-Raf signaling pathway was also involved in PCL-induced autophagy as the negative regulator. In addition, we found that class I phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway could play the negative regulator in PCL-induced apoptosis and autophagy. Taken together, these results demonstrate that PCL induces murine fibrosarcoma L929 cell apoptosis and autophagy via blocking Ras-Raf and PI3K-Akt signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Fibrosarcoma / metabolism
  • Fibrosarcoma / pathology
  • Fibrosarcoma / ultrastructure
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Indoles / pharmacology
  • Mice
  • Microscopy, Electron, Transmission
  • Phenols / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Lectins / pharmacology*
  • Polyenes / pharmacology
  • Polygonatum / metabolism
  • Polyunsaturated Alkamides / pharmacology
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Tetrazoles / pharmacology
  • Time Factors
  • Wortmannin
  • raf Kinases / antagonists & inhibitors
  • raf Kinases / metabolism
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / metabolism

Substances

  • Androstadienes
  • Heterocyclic Compounds, 4 or More Rings
  • Indoles
  • KP372-1
  • Phenols
  • Phosphoinositide-3 Kinase Inhibitors
  • Plant Lectins
  • Polyenes
  • Polyunsaturated Alkamides
  • Tetrazoles
  • Proto-Oncogene Proteins c-akt
  • raf Kinases
  • ras Proteins
  • manumycin
  • 5-iodo-3-((3,5-dibromo-4-hydroxyphenyl)methylene)-2-indolinone
  • Wortmannin