title: Doxorubicin exerts cytotoxic effects through cell cycle arrest and Fas-mediated cell death.
abstract: Doxorubicin (DOX) is involved in the induction of DNA damage, inhibition of cell proliferation, impairment of mitochondria, and cell death. To determine the biological effects of DOX in murine lymphocytes, we analyzed cell proliferation, cell cycle status, and apoptosis in Ba/F3 and EL4 lymphoid cells. DOX treatment resulted in significant cellular morphological alteration with increased intracellular granularity and cell size. DOX inhibited cell proliferation through cell cycle arrest at the G(2)/M phase as well as by cell death. In addition, DOX treatment dramatically upregulated Fas expression and enhanced caspase activation to promote intracellular apoptotic signaling for cell death. Treatment with an agonistic antibody stimulated Fas and accelerated the cell death effects. In conclusion, we demonstrate that DOX induces cell cycle arrest and apoptosis by increased Fas expression and ultimately results in enhanced cell death.
authors.affiliation: Graduate School of Life Science and Biotechnology, Pochon CHA University, CHA Stem Cell Institute, Seoul, Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Dong-Ku
authors.initials: DK
authors.lastname: Kim
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D049108:Cell Enlargement / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D053222:Fas Ligand Protein / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D053222:Fas Ligand Protein; D019014:fas Receptor; D004317:Doxorubicin; D020169:Caspases