Betulinic acid induces DNA damage and apoptosis in SiHa cells

Mutat Res Genet Toxicol Environ Mutagen. 2018 Apr;828:1-9. doi: 10.1016/j.mrgentox.2018.02.003. Epub 2018 Feb 10.

Abstract

Betulinic acid (BA) is a naturally occurring terpenoid found principally in the bark of birch trees as well as in numerous other plants. BA is reported to inhibit cancer progression and induce apoptosis in multiple tumor types. In the present study we have investigated the cytotoxicity and potential genotoxicity of BA in SiHa cells. The cell viability was measured by using MTT assay and the morphological changes, DNA damage, changes in cell cycle and mitochondrial membrane potential (MMP) were used for the assessment of apoptosis. BA was shown to destroy SiHa cells preferentially in a concentration dependent manner with a 50% inhibition of the cells at 39.83 μg/ml. The growth inhibition of the cells by BA was coupled with DNA strand breaks, morphological changes, disruption of MMP, reactive oxygen species (ROS) generation and the cell arrest at G0/G1 stage of cell cycle. BA induced apoptosis in SiHa cells was confirmed by positive Annexin V FITC-PI staining. Our results indicate that BA effectively induced DNA damage and apoptosis in SiHa cells. The mechanism of apoptosis was caspase independent and through mitochondrial pathways.

Keywords: Apoptosis; Betulinic acid; Cervical cancer cells; DNA damage; Mitochondrial membrane potential.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Damage / drug effects*
  • Female
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mutagenicity Tests
  • Pentacyclic Triterpenes
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • Reactive Oxygen Species / metabolism
  • Triterpenes / pharmacology*
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / pathology

Substances

  • Antineoplastic Agents, Phytogenic
  • Pentacyclic Triterpenes
  • Reactive Oxygen Species
  • Triterpenes
  • betulinic acid
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • CASP3 protein, human
  • Caspase 3