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.
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.
Choi
Su-La
SL
Clinical Biochemistry Lab, Department of Pharmacy, College of Pharmacy, Chungnam National University, Daejon, Korea.
Choi
Yun-Sil
YS
Kim
Young-Kwan
YK
Sung
Nack-Do
ND
Kho
Chang-Won
CW
Park
Byong-Chul
BC
Kim
Eun-Mi
EM
Lee
Jung-Hyung
JH
Kim
Kyung-Mee
KM
Kim
Min-Yung
MY
Myung
Pyung-Keun
PK
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D053471:Caspases, Initiator; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D051858:Forkhead Transcription Factors; D006801:Humans; D008545:Melanoma; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D040901:Proteomics; D012097:Repressor Proteins / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000494:pharmacology*
D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C106158:FOXN3 protein, human; D051858:Forkhead Transcription Factors; C511721:N-(4-methyl)phenyl-O-(4-methoxy)phenylthionocarbamate; D012097:Repressor Proteins; D013859:Thiocarbamates; D017027:Protein Tyrosine Phosphatases; C093516:CASP4 protein, human; D020169:Caspases; D053471:Caspases, Initiator