Plumbagin enhances TRAIL-mediated apoptosis through up-regulation of death receptor in human melanoma A375 cells.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-cancer agent. However, emergence of drug resistance limits its potential use. Plumbagin is a natural quinonoid compound isolated from plant. In this study, induced apoptosis effect of the combined treatment with plumbagin and TRAIL on human melanoma A375 cell line was examined and possible mechanism was investigated. The cells were divided into four groups: control group, plumbagin group (plumbagin, 5 or 10 mumol/L), TRAIL group (TRAIL, 30 ng/mL) and plumbagin+TRAIL group (combined treatment group). The apoptosis, and the expression of DR4 and DR5 were detected by flow cytometry. The activities of caspase-8 and caspase-3 were determined by colorimetric assay. The results showed that the apoptosis rate was 8.3% in TRAIL group, 10.35%-16.94% in plumbagin group and 52.39%-65.39% in combined treatment group, respectively, with the difference being significant between combined treatment group and plumbagin or TRAIL group (P<0.05 for each). Moreover, plumbagin alone could markedly up-regulate DR5 mRNA and protein expression, and slightly increase DR4 mRNA and protein expression. Treatment of human melanoma A375 cells with plumbagin resulted in the activation of Caspase-3, but not Caspase-8. These results suggest that plumbagin might be useful for TRAIL-based treatment for melanoma.
Li
Jiawen
J
Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. shenqin1220@tom.com
Shen
Qin
Q
Peng
Rui
R
Chen
Rongyi
R
Jiang
Ping
P
Li
Yanqiu
Y
Zhang
Li
L
Lu
Jingjing
J
D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D006801:Humans; D008545:Melanoma / Q000473:pathology*; D009285:Naphthoquinones / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D012878:Skin Neoplasms / Q000473:pathology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D009285:Naphthoquinones; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8; C014758:plumbagin