Total triterpenoids from Ganoderma Lucidum suppresses prostate cancer cell growth by inducing growth arrest and apoptosis

J Huazhong Univ Sci Technolog Med Sci. 2015 Oct;35(5):736-741. doi: 10.1007/s11596-015-1499-x. Epub 2015 Oct 22.

Abstract

In this study, one immortalized human normal prostatic epithelial cell line (BPH) and four human prostate cancer cell lines (LNCaP, 22Rv1, PC-3, and DU-145) were treated with Ganoderma Lucidum triterpenoids (GLT) at different doses and for different time periods. Cell viability, apoptosis, and cell cycle were analyzed using flow cytometry and chemical assays. Gene expression and binding to DNA were assessed using real-time PCR and Western blotting. It was found that GLT dose-dependently inhibited prostate cancer cell growth through induction of apoptosis and cell cycle arrest at G1 phase. GLT-induced apoptosis was due to activation of Caspases-9 and -3 and turning on the downstream apoptotic events. GLT-induced cell cycle arrest (mainly G1 arrest) was due to up-regulation of p21 expression at the early time and down-regulation of cyclin-dependent kinase 4 (CDK4) and E2F1 expression at the late time. These findings demonstrate that GLT suppresses prostate cancer cell growth by inducing growth arrest and apoptosis, which might suggest that GLT or Ganoderma Lucidum could be used as a potential therapeutic drug for prostate cancer.

Keywords: Ganoderma Lucidum triterpenoids; apoptosis; cell cycle arrest; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 9 / genetics
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dose-Response Relationship, Drug
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • G1 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Nucleosomes / drug effects
  • Nucleosomes / metabolism
  • Nucleosomes / pathology
  • Plant Extracts / chemistry
  • Prostate / drug effects*
  • Prostate / metabolism
  • Prostate / pathology
  • Reishi / chemistry*
  • Signal Transduction
  • Triterpenes / isolation & purification
  • Triterpenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • CCND1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Nucleosomes
  • Plant Extracts
  • Triterpenes
  • Cyclin D1
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9