Lantabetulic acid derivatives induce G1 arrest and apoptosis in human prostate cancer cells

Arch Pharm (Weinheim). 2014 Jan;347(1):42-53. doi: 10.1002/ardp.201300224. Epub 2013 Nov 18.

Abstract

Ten new lantabetulic acid (1) derivatives 2-11 were synthesized and their cytotoxicities against human prostate cancer cells were evaluated. PC3 cells treated with 10 μM 8 exhibited the most potent G1 phase arrest. In addition, 10 μM 8 markedly decreased the levels of cyclin E and cdk2 and caused an increase in the p21 and p27 levels, while 20 μM 8 mainly led to cell death through the apoptotic pathway, which correlated with an increase in reactive oxygen species levels, decreased expression levels of Bcl-2 and caspase-8, the induction of mitochondrial changes, and decreased levels of cytochrome c in mitochondria. The dual action of 8 could provide a new approach for the development of chemotherapeutic drugs.

Keywords: Apoptosis; Cytotoxicity; G1 arrest; Lantabetulic acid; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondria / pathology
  • Molecular Structure
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Reactive Oxygen Species / metabolism
  • Time Factors
  • Triterpenes / chemical synthesis
  • Triterpenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • Reactive Oxygen Species
  • Triterpenes