title: Smac is another pathway in the anti-tumour activity of Trichosanthin and reverses Trichosanthin resistance in CaSki cervical cancer cells.
abstract: Trichosanthin (TCS), or Tin Hua Fen, is a renowned traditional Chinese medicine and is still used in Chinese clinics for midterm abortion and the treatment of choriocarcinoma. Many studies have demonstrated that TCS has anti-tumour action as a type I ribosome-inactivating protein. We hypothesized that there is another pathway of the anti-tumour activity of TCS. cDNA array analysis was applied to profile changes in gene expression of human CaSki in response to TCS stimulation. Smac, a mitochondrial protein, was identified as the highly upregulated protein in response to TCS treatment. The mRNA and protein levels of Smac were determined by real-time RT-PCR and Western blotting respectively. We analysed the methylation status of Smac using methylation-specific PCR (MSP) and indicates that TCS promotes Smac demethylation and increases its expression in cervical CaSki cells. Tumour cells develop resistance to TCS during prolonged treatment, as with other classic chemotherapeutic agents. Smac expression was downregulated and Twist was upregulated in TCS-resistant cells. These results indicate that TCS has demethylating activity and that Smac is involved in both TCS response and TCS resistance.
authors: Department of General Surgery, Yichang Central People's Hospital and The First Affiliated Hospital of China Three Gorges University, 443002 Yichang, People's Republic of China. Electronic address: leileicui@126.com.
authors: Lei
authors: L
authors: Cui
authors: Department of Biochemistry and Molecular biology, College of Basic Medicine, Wuhan University, Wuhan 430071, People's Republic of China.
authors: Jian
authors: J
authors: Song
authors: Institute of Molecular Biology of Three Gorges University, Yichang, People's Republic of China.
authors: Liting
authors: L
authors: Wu
authors: Institute of Molecular Biology of Three Gorges University, Yichang, People's Republic of China.
authors: Liming
authors: L
authors: Huang
authors: Institute of Molecular Biology of Three Gorges University, Yichang, People's Republic of China.
authors: Yanlin
authors: Y
authors: Wang
authors: Institute of Molecular Biology of Three Gorges University, Yichang, People's Republic of China.
authors: Yingdi
authors: Y
authors: Huang
authors: Institute of Molecular Biology of Three Gorges University, Yichang, People's Republic of China.
authors: Han
authors: H
authors: Yu
authors: Institute of Molecular Biology of Three Gorges University, Yichang, People's Republic of China.
authors: Yiling
authors: Y
authors: Huang
authors: Institute of Molecular Biology of Three Gorges University, Yichang, People's Republic of China.
authors: C C
authors: CC
authors: You
authors: Institute of Molecular Biology of Three Gorges University, Yichang, People's Republic of China.
authors: Jiayou
authors: J
authors: Ye
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000187:drug effects*; D015978:Trichosanthin / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C412403:DIABLO protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D015978:Trichosanthin
keywords: Anti-tumour activity; Smac; Trichosanthin