title: Anticancer Activity of Cobra Venom Polypeptide, Cytotoxin-II, against Human Breast Adenocarcinoma Cell Line (MCF-7) via the Induction of Apoptosis.
abstract: OBJECTIVE
  Breast cancer is a significant health problem worldwide, accounting for a quarter of all cancer diagnoses in women. Current strategies for breast cancer treatment are not fully effective, and there is substantial interest in the identification of novel anticancer agents especially from natural products including toxins. Cytotoxins are polypeptides found in the venom of cobras and have various physiological effects. In the present study, the anticancer potential of cytotoxin-II against the human breast adenocarcinoma cell line (MCF-7) was investigated.
  
  
  METHODS
  The cytotoxic effects of cytotoxin-II were determined by morphological analysis and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The mode and mechanism of cell death were investigated via acridine orange/ethidium bromide (AO/EtBr) double staining, flow cytometric analysis of cell death, detection of mitochondrial membrane potential, measurement of intracellular reactive oxygen species (ROS), annexin V/propidium iodide staining, and caspase-9 activity assays.
  
  
  RESULTS
  The half maximal inhibitory concentration (IC50) of cytotoxin-II in MCF-7 cells was 4.18±1.23 µg/mL, while the value for cisplatin was approximately 28.02±1.87 µg/mL. Morphological analysis and AO/EtBr double staining showed typical manifestations of apoptotic cell death (in doses lower than 8 µg/mL). Dose- and time-dependent ROS generation, loss of mitochondrial membrane potential, caspase-9 activation, and cell cycle arrest were observed in their respective tests.
  
  
  CONCLUSIONS
  In conclusion, cytotoxin-II has potent anticancer effects in the MCF-7 cell line, which are induced via the intrinsic pathways of apoptosis. Based on these findings, cytotoxin-II is a suitable choice for breast cancer treatment.
authors.affiliation: Department of Toxicology, Shahid Beheshti University of Medical Sciences School of Pharmacy, Tehran, Iran.
authors.forename: Karim
authors.initials: K
authors.lastname: Ebrahim
authors.affiliation: Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Farshad H
authors.initials: FH
authors.lastname: Shirazi
authors.affiliation: Department of Toxicology, Shahid Beheshti University of Medical Sciences School of Pharmacy, Tehran, Iran.
authors.forename: Hosein
authors.initials: H
authors.lastname: Vatanpour
authors.affiliation: Razi Vaccine and Serum Research Institute, Karaj, Iran.
authors.forename: Abas
authors.initials: A
authors.lastname: Zare
authors.affiliation: Department of Pharmaceutical Chemistry, Shahid Beheshti University of Medical Sciences School of Pharmacy, Tehran, Iran.
authors.forename: Farzad
authors.initials: F
authors.lastname: Kobarfard
authors.affiliation: Razi Vaccine and Serum Research Institute, Karaj, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Rabiei
keywords: Apoptosis; Breast neoplasms; Cytotoxins; Snakes; Venoms