Evaluation of the antitumoral effect of dihydrocucurbitacin-B in both in vitro and in vivo models |
| |
Authors: | Jarbas Mota Siqueira Andressa Córneo Gazola Mareni Rocha Farias Lëonid Volkov Nathalie Rivard Artur José de Brum-Fernandes Rosa Maria Ribeiro-do-Valle |
| |
Institution: | 1. Department of Pharmacology, CCB, Bloco “D”, Federal University of Santa Catarina, Campus Universitário Trindade, Florianópolis, SC, CEP 88.049-900, Brazil 2. Department of Pharmaceutical Sciences, Federal University of Santa Catarina, Florianópolis, SC, Brazil 3. Department of Immunology, Faculté de Medecine, Université Sherbrooke, Sherbrooke, QC, Canada 4. Department of Anatomy and Cell Biology, Faculté de Medecine, Université Sherbrooke, Sherbrooke, QC, Canada 5. Division of Rheumatology, Faculté de Medecine, Université de Sherbrooke, Sherbrooke, QC, Canada
|
| |
Abstract: | Aims We evaluated both in vitro and in vivo antitumoral properties of an isolated compound from Wilbrandia ebracteata, dihydrocucurbitacin-B (DHCB), using B16F10 cells (murine melanoma).
Materials and methods We made use of MTT and 3H-Thymidine assays to investigate the cell viability and cell proliferation, flow cytometry analysis to monitor cell cycle
and apoptosis, western blot analysis to evaluate the expression of cell cycle proteins, imunofluorescence analysis and in
vivo tumor growth and metastasis.
Results Dihydrocucurbitacin-B significantly reduced cell proliferation without important effects on cells viability. DHCB lead cells
to accumulate in G2/M phases accompanied by the appearance of polyploid cells, confirmed by fluorescence assays that demonstrated
a remarkable alteration in the cell cytoskeleton and formation of binuclear cells. Annexin-V-FITC incorporation demonstrated
that DHCB did not induce apoptosis. About 10 μg/mL DHCB was found to decrease cyclin-A, and especially in cyclin-B1. The in
vivo experiments showed that DHCB treatment (once a day up to 12 days; p.o.) was able to reduce the tumor growth and lung
metastasis up to 83.5 and 50.3%, respectively.
Conclusions Dihydrocucurbitacin-B reduces cell proliferation due to a decrease in the expression of cyclins, mainly cyclin-B1 and disruption
of the actin cytoskeleton, arresting B16F10 cells in G2/M phase. Taken together, the in vitro and in vivo experiments suggest
that DHCB was effective against cancer, however, it remains to be proved if DHCB will be a good candidate for drug development. |
| |
Keywords: | Dihydrocucurbitacin-B Cytoskeleton Cyclins Wilbrandia ebracteata |
本文献已被 SpringerLink 等数据库收录! |
|