Therapeutic efficacy of natural dipeptide carnosine against human cervical carcinoma cells

J Mol Recognit. 2016 Sep;29(9):426-35. doi: 10.1002/jmr.2541. Epub 2016 Mar 22.

Abstract

Natural substances have been attracted several researchers in the recent years, because of its potential antioxidant, anti-inflammatory and anti-cancer properties. We have investigated the effect of carnosine on cell viability, apoptosis, DNA damage, reactive oxygen species (ROS) and caspase 3 enzyme expression in human cervical carcinoma and Madin-Darby Kidney Cells (MDCK) cells. Carnosine inhibited cancer cell growth up to 23%. ROS level was increased up to 30 and 31% in MDCK and HeLa cells respectively. Tunnel assay showed 42 and 14% of positive apoptotic cells in cancer and normal cells respectively. The alteration in mitochondrial and nuclear morphology was determined. The extended lace-like network of normal mitochondria found in control cells. Carnosine treatment significantly altered the mitochondrial morphology of normal cervical carcinoma cell. Mitochondria were condensed clump structures in carnosine treated cancer cells. Carnosine reduced the number of colonies of cervical carcinoma cells. Caspase 3 expression was corresponded to the appearance of immunofluorescence in the cytoplasm. Caspase 3 expression was gradually increased in cervical carcinoma cells. In Silico, docking study was performed to recognize the binding activity of carnosine against a subunit of the caspase 3, and carnosine was able to bind to the drug binding pocket of caspase 3. The glide energy is -5.2 kcal/mol, suggesting the high binding affinity of carnosine to caspase 3. Taking all these data together, the natural dipeptide L-carnosine could be a suitable antiproliferative agent in cervical carcinoma cells. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: HeLa cells; L-carnosine; MDCK cells; anti-proliferative; caspase 3.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma / drug therapy*
  • Carnosine / pharmacology*
  • Caspase 3 / biosynthesis
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • DNA Damage / drug effects
  • Dogs
  • Female
  • Fluorescent Antibody Technique
  • HeLa Cells
  • Humans
  • Madin Darby Canine Kidney Cells
  • Mitochondria / physiology
  • Molecular Docking Simulation
  • Reactive Oxygen Species / metabolism
  • Uterine Cervical Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Reactive Oxygen Species
  • Carnosine
  • Caspase 3