Evaluation of genotoxic and apoptotic potential of Hypericum adenotrichum Spach. in vitro

Regul Toxicol Pharmacol. 2016 Feb:74:137-46. doi: 10.1016/j.yrtph.2015.11.010. Epub 2015 Nov 23.

Abstract

Hypericum adenotrichum Spach. is an endemic plant from Turkey that is also used in folk medicine. In this study, following analyses of its chemical composition, the genotoxic/antigenotoxic effects of the methanol extract of H. adenotrichum in human lymphocyte culture were investigated using in vitro sister chromatid exchange, micronucleus and comet assays. In addition, the anti-growth effect of the extract was investigated in human breast cancer cell lines (MCF-7 and MDA-MB-231) using MTT and ATP viability assays. The mode of cell death was determined using fluorescence microscopy and biochemical methods. We found that the H. adenotrichum extract demonstrated cytotoxic and genotoxic effects in a cell type-dependent manner. At selected doses (125-500 μg/ml), the H. adenotrichum extract exhibited significant genotoxic activity in human lymphocytes, whereas it showed anti-growth effects on cancer cell lines between 0.2 and 100 μg/ml concentrations. The mode of cell death in cancer cells was shown to be apoptosis due to the presence of pyknotic nuclei, the cleavage of poly-(ADP-ribose) polymerase (PARP) and/or the activation of caspase-3. These results suggest that H. adenotrichum might show both cytotoxic and genotoxic effects depending on the cell type. This should be taken into account in its use for therapeutic purposes.

Keywords: Apoptosis; Breast cancer; Genotoxicity; Hypericum adenotrichum.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adolescent
  • Adult
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / toxicity
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Comet Assay
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypericum / chemistry*
  • Lymphocytes / drug effects*
  • Lymphocytes / pathology
  • MCF-7 Cells
  • Male
  • Micronuclei, Chromosome-Defective / chemically induced*
  • Micronucleus Tests
  • Microscopy, Fluorescence
  • Mutagenicity Tests*
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plant Extracts / toxicity
  • Plants, Medicinal
  • Risk Assessment
  • Sister Chromatid Exchange / drug effects
  • Young Adult

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Adenosine Triphosphate