title: Apoptosis is the most efficient death-pathway in tumor cells after topoisomerase II inhibition.
abstract: OBJECTIVE
  To compare the efficiency of apoptosis and other modes of cell death in killing tumor cells after the induction of DNA damage by topoisomerase inhibitors like etoposide.
  
  
  METHODS
  This study was carried out in the Tumor Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt, from September 2005 to August 2007. The breast cancer MCF7, the cervix carcinoma, human cervical adenocarcinoma Hela, and the brain tumor U251 cell lines were exposed to etoposide. Apoptosis was detected using the flow cytometry and the DNA ladder formation methods. Cell viability was determined by a colorimetric assay, and the residual DNA double-strand breaks dsb were measured by gel electrophoresis.
  
  
  RESULTS
  The Hela cells were the most, the MCF7's were moderately, whereas the U251's were the least sensitive to etoposide. Apoptosis was detected only in Hela cells whereas the other 2 cell lines showed a very low level of apoptosis only 3% increase above the control cells. At equitoxic drug concentrations namely IC50, the Hela cells showed the lowest amount of non-repaired DNA dsb, and the MCF7's showed the highest amount, whereas the U251 cells showed a moderate amount.
  
  
  CONCLUSIONS
  These results indicate that although other modes of cell death exist, apoptosis is the most efficient and requires lower drug concentrations and fewer numbers of non-repaired dsb to give the same killing effect. Clinically, this means that tumors that can execute apoptosis may require lower doses of topoisomerase inhibitors than those that lost the ability to exercise apoptosis.
authors.affiliation: Department of Tumor Biology, National Cancer Institute, Cairo University, Cairo, Egypt. el_awady_raafat@hotmail.com
authors.forename: Raafat A
authors.initials: RA
authors.lastname: El-Awady
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Ali
authors.forename: Ekram M
authors.initials: EM
authors.lastname: Saleh
authors.forename: Fayek M
authors.initials: FM
authors.lastname: Ghaleb
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D016923:Cell Death; D045744:Cell Line, Tumor / Q000187:drug effects* / Q000473:pathology; D005047:Etoposide / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D059005:Topoisomerase II Inhibitors
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D059005:Topoisomerase II Inhibitors; D005047:Etoposide