title: Genotoxic and cytotoxic effects of doxorubicin and silymarin on human hepatocellular carcinoma cells.
abstract: The aim of this study was to investigate genotoxic and cytotoxic effects of doxorubicin, silymarin, or in combination on HepG2 cells for 24 and 48 h. Both doxorubicin and silymarin caused dose-dependent inhibition of cell proliferation. After 48 h of treatment, doxorubicin application caused dramatically increased ratio of apoptotic cells. Both 24 and 48 h of silymarin and doxorubicin-silymarin combination caused significant increases in the rate of apoptotic cells. Applications of doxorubicin and silymarin separately for 24 h led to deoxyribonucleic acid (DNA) damages. After 48 h of incubation, doxorubicin-induced genotoxic damage was 2-fold higher than the silymarin-induced damage. After 24 and 48 h, DNA damage in response to combined applications of doxorubicin and silymarin was indifferent from silymarin- and doxorubicin-induced damage respectively. There was not any difference in genotoxicity levels between incubation periods in combined applications of doxorubicin and silymarin. Lipid peroxidation levels increased in all applications. Biopharmacotherapy with chemotherapeutic agents are of interest in the issue of adjuvant therapy. Here, we demonstrate in vitro potential genotoxic and cytotoxic antitumor effect of silymarin on HepG2 cells at achievable plasma level concentrations.
authors.affiliation: Department of Medical Biology, Faculty of Medicine, Baskent University, Ankara, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Yurtcu
authors.affiliation: Institute of Transplantation and Gene Sciences, Baskent University, Ankara, Turkey.
authors.forename: Öd
authors.initials: Ö
authors.lastname: İşeri
authors.affiliation: Institute of Transplantation and Gene Sciences, Baskent University, Ankara, Turkey Department of Medical Genetics, Faculty of Medicine, Baskent University, Ankara, Turkey feridesahin@hotmail.com.
authors.forename: Fi
authors.initials: F
authors.lastname: Sahin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009153:Mutagens / Q000494:pharmacology*; D012838:Silymarin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009153:Mutagens; D012838:Silymarin; D004317:Doxorubicin
keywords: Doxorubicin; comet assay; hepatocellular carcinoma; lipid peroxidation; silymarin