Reversion of P-glycoprotein-mediated multidrug resistance by diallyl trisulfide in a human osteosarcoma cell line.
Diallyl trisulfide (DATS), the main sulfuric compound in garlic, has been shown to have antitumor effects. The present study aimed to ascertain whether DATS reverses the drug resistance of human osteosarcoma cells in vitro and to investigate its potential mechanisms. Human osteosarcoma U2-OS cells were treated with different concentrations of DATS. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while P-glycoprotein (P-gp) expression and the proportion of apoptotic cells were measured by flow cytometry. Morphological changes were observed under an optical microscope. Νuclear factor-κB (NF-κB) and inhibitor of NF-κB (IκB) activities were measured by PCR and western blot analysis. Results showed that the proliferation of U2-OS cells treated with different concentrations of DATS was significantly decreased in a concentration- and time-dependent manner. DATS increased the toxic effect of adriamycin on U2-OS cells. Moreover, P-gp expression was decreased and the apoptosis rate was increased in a concentration-dependent manner following treatment of DATS. Additionally, NF-κB activity was inhibited by DATS while expression of IκB was increased. Our data clearly suggest that DATS has significant anticancer effects on human osteosarcoma cells. The potential mechanisms include reducing the multidrug resistance and inducing apoptosis. NF-κB suppression may be involved in DATS-induced inhibition of cell proliferation.
Department of Emergency Surgery, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Zhiyong
Z
Wang
Department of Urinary Medicine, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Qing
Q
Xia
Shouguang Centre for Disease Control and Prevention, Shouguang, Shandong 262700, P.R. China.
Jia
J
Cui
Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, P.R. China.
Yutao
Y
Diao
Department of Orthopedics, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.
Jianmin
J
Li
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000498:Allyl Compounds / Q000008:administration & dosage; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D013440:Sulfides / Q000008:administration & dosage
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000498:Allyl Compounds; D016328:NF-kappa B; D013440:Sulfides; C042577:diallyl trisulfide