Molecular switch role of Akt in Polygonatum odoratum lectin-induced apoptosis and autophagy in human non-small cell lung cancer A549 cells

PLoS One. 2014 Jul 3;9(7):e101526. doi: 10.1371/journal.pone.0101526. eCollection 2014.

Abstract

Polygonatum odoratum lectin (POL), isolated from traditional Chinese medicine herb (Mill.) Druce, has drawn rising attention due to its wide biological activities. In the present study, anti-tumor effects, including apoptosis- and autophagy-inducing properties of POL, were determined by a series of cell biology methods such as MTT, cellular morphology observation, flow cytometry, immunoblotting. Herein, we found that POL could simultaneously induce apoptosis and autophagy in human non-small cell lung cancer A549 cells. POL initiated apoptosis through inhibiting Akt-NF-κB pathway, while POL triggered autophagy via suppressing Akt-mTOR pathway, suggesting the molecular switch role of Akt in regulating between POL-induced apoptosis and autophagy. Moreover, ROS was involved in POL-induced inhibition of Akt expression, and might therefore mediate both apoptosis and autophagy in A549 cells. In addition, POL displayed no significant cytotoxicity toward normal human embryonic lung fibroblast HELF cells. Due to the anti-tumor activities, POL might become a potent anti-cancer drug in future therapy, which might pave the way for exploring GNA-related lectins into effective drugs in cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line
  • Drugs, Chinese Herbal / toxicity
  • HeLa Cells
  • Humans
  • Lectins / chemistry
  • Lectins / toxicity*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Mannose / pharmacology
  • Membrane Potential, Mitochondrial / drug effects
  • NF-kappa B / metabolism
  • Polygonatum / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Drugs, Chinese Herbal
  • Lectins
  • NF-kappa B
  • Reactive Oxygen Species
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Mannose

Grants and funding

This work was supported in part by the National Natural Science Foundation of China (No. 81373311, No. 31300674, No. 30970643, No. 81173093 and No. J1103518), the Special Program for Youth Science and the Technology Innovative Research Group of Sichuan Province, China (No. 2011JTD0026). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.