Proteomic analysis and the antimetastatic effect of N-(4-methyl)phenyl-O-(4-methoxy) phenyl-thionocarbamate-induced apoptosis in human melanoma SK-MEL-28 cells.

Abstract

We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompany N-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-kappaB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.

• Authors: Su-La Choi, Yun-Sil Choi, Young-Kwan Kim, Nack-Do Sung, Chang-Won Kho, Byong-Chul Park, Eun-Mi Kim, Jung-Hyung Lee, Kyung-Mee Kim, Min-Yung Kim, Pyung-Keun Myung
• Journal: Archives of pharmacal research (Arch Pharm Res) Vol. 29 Issue 3 Pg. 224-34 (Mar 2006) ISSN: 0253-6269 [Print] Korea (South)
• PMID: 16596996 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cell Cycle Proteins
• FOXN3 protein, human
• Forkhead Transcription Factors
• N-(4-methyl)phenyl-O-(4-methoxy)phenylthionocarbamate
• Repressor Proteins
• Thiocarbamates
• Protein Tyrosine Phosphatases
• CASP4 protein, human
• Caspases
• Caspases, Initiator

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Apoptosis
• Caspases (metabolism)
• Caspases, Initiator
• Cell Cycle Proteins (metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Forkhead Transcription Factors
• Humans
• Melanoma
• Protein Tyrosine Phosphatases (metabolism)
• Proteomics
• Repressor Proteins (metabolism)
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• Thiocarbamates (chemical synthesis, pharmacology)