A small compound that inhibits tumor necrosis factor-alpha-induced matrix metalloproteinase-9 upregulation.
Matrix metalloproteinase-9 (MMP-9) is critically involved in the tumor invasion and metastasis processes. Since TNF-alpha plays a crucial role in the regulation of MMP-9 expression, the development of molecules capable of modulating TNF-alpha-induced signaling is an issue of concern. We identified a novel synthetic compound that inhibits TNF-alpha-induced MMP-9 upregulation in the HT1080 human fibrosarcoma cell line. The active compound SM-7368 inhibited TNF-alpha-induced MMP-9 upregulation in a concentration-dependent manner and showed maximal activity at 10 microM. SM-7368 inhibited TNF-alpha-induced MMP-9 mRNA transcript accumulation and protein expression. We also found that SM-7368 strongly inhibits TNF-alpha-induced NF-kappaB activity but not AP-1 activity. Moreover, we found that SM-7368 strongly inhibits the TNF-alpha-induced invasion of HT1080 human fibrosarcoma cell line. Taken together, our results demonstrate that SM-7368 is a synthetic compound that inhibits TNF-alpha-induced MMP-9 expression, and thus SM-7368 should be useful for the development of chemotherapies targeting TNF-alpha-mediated tumor invasion and metastasis.
Lee
Ha Young
HY
Medical Research Center for Cancer Molecular Therapy and Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Park
Kyoung Sun
KS
Kim
Mi-Kyoung
MK
Lee
Taehoon
T
Ryu
Sung Ho
SH
Woo
Kyung Jin
KJ
Kwon
Taeg Kyu
TK
Bae
Yoe-Sik
YS
D001549:Benzamides / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005354:Fibrosarcoma / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism*; D013844:Thiazoles / Q000008:administration & dosage* / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*; D015854:Up-Regulation / Q000187:drug effects
D001549:Benzamides; D016328:NF-kappa B; C505226:SM 7368; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9