Vesnarinone inhibits angiogenesis and tumorigenicity of human oral squamous cell carcinoma cells by suppressing the expression of vascular endothelial growth factor and interleukin-8.
Vesnarinone is a synthesized positive oral inotropic agent that has multiple biological activities on mammalian cells both in vitro and in vivo. This agent has been reported in relation to its antitumor effect with apoptosis-inducing activity. In the present study, we determined whether vesnarinone could suppress angiogenesis and growth of human oral squamous cell carcinoma cells in vitro and in vivo. Vesnarinone significantly inhibited the in vitro and in vivo expression of two major proangiogenic molecules, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in cultured cells and in cells implanted into the subcutaneous tissue of nude mice. Also, vesnarinone inhibited the nuclear factor-kappa B (NF-kappaB) activity in human oral squamous cell carcinoma cells in vitro. The decreased expression of VEGF and IL-8 correlated with decreased tumorigenicity and decreased vascularization of lesions in vivo. These findings suggest that vesnarinone can suppress the angiogenesis and growth of oral squamous cell carcinoma cells by inhibiting the expression of VEGF and IL-8 involved in blockade of NF-kappaB activity.
Harada
Koji
K
Second Department of Oral and Maxillofacial Surgery, University of Tokushima, School of Dentistry, Tokushima 770-8504, Japan. harako@dent.tokushima-u.ac.jp
Supriatno
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000098:blood supply / Q000473:pathology / Q000517:prevention & control*; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D011485:Protein Binding / Q000187:drug effects; D011719:Pyrazines; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000970:Antineoplastic Agents; D016209:Interleukin-8; D016328:NF-kappa B; D011719:Pyrazines; D011804:Quinolines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C041667:vesnarinone