Triptolide inhibits cyclooxygenase-2 and inducible nitric oxide synthase expression in human colon cancer and leukemia cells.
Triptolide (TP), a traditional Chinese medicine, has been reported to be effective in the treatment of autoimmune diseases and exerting antineoplastic activity in several human tumor cell lines. This study investigates the antitumor effect of TP in human colon cancer cells (SW114) and myelocytic leukemia (K562), and elucidates the possible molecular mechanism involved. SW114 and K562 cells were treated with different doses of TP (0, 5, 10, 20, or 50 ng/ml). The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Results demonstrated that TP inhibited the proliferation of both tumor cell lines in a dose-dependent manner. To further investigate its mechanisms, the products prostaglandin E(2) (PGE(2)) and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay (ELISA). Our data showed that TP strongly inhibited the production of NO and PGE(2). Consistent with these results, the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was up-regulated both at the mRNA level and the protein expression level, as shown by real-time RT-PCR and Western blotting. These results indicated that the inhibition of the inflammatory factor COX-2 and iNOS activity could be involved in the antitumor mechanisms of TP.
Tong
Xiangmin
X
Institute of Hematologic Disease, Department of Hematology, First Affiliated Hospital, Medical School, Zhejiang University, Hangzhou 310003, China. yaohp2001@yahoo.com.cn.
Zheng
Shui'er
S
Jin
Jie
J
Zhu
Lifen
L
Lou
Yinjun
Y
Yao
Hangping
H
D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002681:China; D003110:Colonic Neoplasms / Q000201:enzymology*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D017931:DNA Primers; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000201:enzymology*; D008516:Medicine, Chinese Traditional; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D010616:Phenanthrenes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects
D052246:Cyclooxygenase 2 Inhibitors; D017931:DNA Primers; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; D012333:RNA, Messenger; C001899:triptolide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2