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Open Access Research

Cytotoxicity, anti-angiogenic, apoptotic effects and transcript profiling of a naturally occurring naphthyl butenone, guieranone A

Victor Kuete12*, Tolga Eichhorn2, Benjamin Wiench2, Benjamin Krusche2 and Thomas Efferth2*

Author Affiliations

1 Department of Biochemistry, Faculty of science, University of Dschang, Dschang, Cameroon

2 Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany

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Cell Division 2012, 7:16  doi:10.1186/1747-1028-7-16

Published: 20 June 2012

Abstract

Background

Malignant diseases are responsible of approximately 13% of all deaths each year in the world. Natural products represent a valuable source for the development of novel anticancer drugs. The present study was aimed at evaluating the cytotoxicity of a naphtyl butanone isolated from the leaves of Guiera senegalensis, guieranone A (GA).

Results

The results indicated that GA was active on 91.67% of the 12 tested cancer cell lines, the IC50 values below 4 μg/ml being recorded on 83.33% of them. In addition, the IC50 values obtained on human lymphoblastic leukemia CCRF-CEM (0.73 μg/ml) and its resistant subline CEM/ADR5000 (1.01 μg/ml) and on lung adenocarcinoma A549 (0.72 μg/ml) cell lines were closer or lower than that of doxorubicin. Interestingly, low cytotoxicity to normal hepatocyte, AML12 cell line was observed. GA showed anti-angiogenic activity with up to 51.9% inhibition of the growth of blood capillaries on the chorioallantoic membrane of quail embryo. Its also induced apotosis and cell cycle arrest. Ingenuity Pathway Analysis identified several pathways in CCRF-CEM cells and functional group of genes regulated upon GA treatment (P < 0.05), the Cell Cycle: G2/M DNA Damage Checkpoint Regulation and ATM Signaling pathways being amongst the four most involved functional groups.

Conclusion

The overall results of this work provide evidence of the cytotoxic potential of GA and supportive data for its possible use in cancer chemotherapy.

Keywords:
Angiogensis; Apoptosis; Cytotoxicity; Guieranone A; Microarray; Pharmacogenomics