Yurtcu E, İşeri Öd, Sahin Fi
Department of Medical Biology, Faculty of Medicine, Baskent University, Ankara, Turkey.
Institute of Transplantation and Gene Sciences, Baskent University, Ankara, Turkey.
Hum Exp Toxicol. 2014 Dec;33(12):1269-76. doi: 10.1177/0960327114529453. Epub 2014 Mar 27.
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.
本研究的目的是调查阿霉素、水飞蓟素或二者联合应用对HepG2细胞24小时和48小时的遗传毒性和细胞毒性作用。阿霉素和水飞蓟素均引起细胞增殖的剂量依赖性抑制。处理48小时后，应用阿霉素导致凋亡细胞比例显著增加。水飞蓟素以及阿霉素 - 水飞蓟素联合应用24小时和48小时均导致凋亡细胞率显著增加。分别应用阿霉素和水飞蓟素24小时导致脱氧核糖核酸（DNA）损伤。孵育48小时后，阿霉素诱导的遗传毒性损伤比水飞蓟素诱导的损伤高2倍。24小时和48小时后，阿霉素和水飞蓟素联合应用引起的DNA损伤分别与水飞蓟素和阿霉素单独应用引起的损伤无差异。阿霉素和水飞蓟素联合应用时，不同孵育时间的遗传毒性水平无差异。所有应用均使脂质过氧化水平升高。化疗药物的生物药物治疗在辅助治疗问题上备受关注。在此，我们证明了在可达到的血浆浓度水平下，水飞蓟素对HepG2细胞具有体外潜在的遗传毒性和细胞毒性抗肿瘤作用。
