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: Lei Cui, Jian Song, Liting Wu, Liming Huang, Yanlin Wang, Yingdi Huang, Han Yu, Yiling Huang, C C You, Jiayou Ye
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 69 Pg. 119-24 (Feb 2015) ISSN: 1950-6007 [Electronic] France
• PMID: 25661347 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Apoptosis Regulatory Proteins
• DIABLO protein, human
• Intracellular Signaling Peptides and Proteins
• Mitochondrial Proteins
• Trichosanthin

Topics

• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis Regulatory Proteins
• Base Sequence
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• CpG Islands (genetics)
• DNA Methylation (drug effects, genetics)
• Down-Regulation (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Humans
• Intracellular Signaling Peptides and Proteins (metabolism)
• Mitochondrial Proteins (metabolism)
• Molecular Sequence Data
• Signal Transduction (drug effects)
• Trichosanthin (pharmacology)
• Up-Regulation (drug effects)
• Uterine Cervical Neoplasms (genetics, metabolism, pathology)