XLIII Annual Meeting of SBBq
th
th
Foz do Iguaçu, PR, Brazil, May 17 to 20 , 2014
Evaluation of a pyranonaphthoquinone against six cancer cell lines and Ehrlich
tumor carcinoma
Oliveira, M.E. 1; Bücker, N.C.F. 2; Rodrigues, P.C. 1; Will, L.S.E.P. 2; Ferreira, S.B 3.;
Pedrosa, C.R. 2; Silva-Jr, F.P. 1
1
Laboratório de Bioquímica de Proteínas e Peptídeos, IOC, FIOCRUZ, Rio de
Janeiro, Brazil; 2 Laboratório de Bioquímica Experimental, UFSC, Florianópolis,
Brazil; 3 Instituto de Química, UFRJ, Rio de Janeiro, Brazil.
INTRODUCTION. Cancer is the second cause of death in the world and the
development of new chemotherapeutics is urgently required. Natural and synthetic
derivatives of quinone have been widely investigated for cancer therapy, especially
naphthoquinones. In this view, SQ17, was identified as a cytotoxic compound among
a series of pyranonaphthoquinones derived from β-lapachone obtained in our group
by chemical synthesis. SQ17 was highly active (IC50 2-5 µM) against four cancer cell
lines (HL-60, SF-295, MDA-MB-435 and HCT-8) and also showed moderate human
DNA topoisomerase I inhibition. In this study, we further investigated the cytotoxic
effects of SQ17 in additional six cancer cell lines (MOLT4, CEM, K562, KG1, HT29
and MCF-7) and evaluated whether it has antitumor effects against the Ehrlich
ascites carcinoma in a mouse model. MATERIALS AND METHODS. For the in vitro
assay, SQ17 was added in varying concentrations to the cell culture disposed in 96well plates and cell death was evaluated after 48h incubation by the Alamar Blue
protocol. For the in vivo assay, mice were inoculated with Ehrlich carcinoma cells; i.p.
treatments (saline; 1 mg/Kg; 2 mg/Kg; 5 mg/Kg) were done every 24h for 9 days.
Tumor growth inhibition was investigated macroscopically from the change in the
abdominal circumference measured on days 0 and 10. Half of all mice were
euthanized and angiogenesis inhibition was evaluated. The remaining animals were
kept alive to evaluate survival parameters. RESULTS AND DISCUSSION. SQ17 was
toxic (IC50 < 20 µM) for all cell lines. In vivo, we found a slight reduction of tumor
growth and angiogenesis in groups treated with SQ17 and mice treated with 5 mg/Kg
had a 39% increase in survival. CONCLUSION. Regardless of the cell line used,
SQ17 showed cytotoxic potential. Besides, the in vivo results indicated this
compound has a promising pharmacological profile thus motivating further studies.
Key-words: cancer; beta-lapachone, pyranonaphtoquinone
Acknowledgments: CNPq; FIOCRUZ; FAPERJ.