Title:S-Phase Kinase-Associated Protein-2 and Nuclear Factor-kappa Beta as Molecular Targets of Oral Burkitt’s Lymphoma Cell Induced by Quinolinone Derivate-Vesnarinone
VOLUME: 15 ISSUE: 2
Author(s): Supriatno*
Affiliation:Department of Oral Medicine, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, 55281, DIY
Keywords:Vesnarinone, chemotactic migration, apoptosis, Burkitt's lymphoma cell, Skp-2, NF-kB.
Abstract:
Background: 3,4-Dihydro-6-[4-{3,4-dimethoxybenzoyl}-1-piperazinyl]-2(1H)-quinolinone
(vesnarinone), a novel inotropic drug with unique and complex mechanisms of action, is
known to show antitumor activity against several human malignancies. In the present study,
vesnarinone-induced signal transduction of S-phase kinase-associated protein 2 (Skp2) and
Nuclear Factor-kappa Beta (NF-κB) as molecular targets of oral malignant Burkitt’s lymphoma
(Raji cells) was evaluated.
Materials and Methods: Raji cells were incubated with vesnarinone at concentrations of 0,
1.25x10-2, 2.50x10-2, or 5.0x10-2 Molar. After 24 h, chemotactic cell migration was examined by
a Boyden chamber kit. Apoptosis induction was observed by caspase-9 colorimetric assay. To
evaluate levels of Skp2, NF-kB, and α-tubulin, Western blot analysis was performed.
Results: Vesnarinone markedly suppressed chemotactic cell migration and significantly induced
apoptosis by increasing the caspase-9 activity of Raji cells through down regulation of Skp2
and NF-κB.
Conclusion: Vesnarinone decreased the expression of Skp2 and NF-κB indicating these molecules
may be targeted for the treatment of oral malignant Burkitt’s lymphoma (BL). The results
of this work offer a promising therapeutic approach for BL tumors.
