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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.

The frequent failure of standard cancer chemotherapy requires the development of novel drugs capable of killing otherwise drug-resistant tumors. Here, we have investigated a chloroform extract ofLaurus nobilisseeds. Fatty acids and 23 constituents of the volatile fraction were identified by gas chromotography/flame ionization detection (GC/FID) and gas chromatography/mass spectrometry (GC/MS), in good agreement with1H NMR (nuclear magnetic resonance) spectrum. Multidrug-resistant P-glycoprotein-expressing CEM/ADR5000 leukemia cells were hypersensitive (collaterally sensitive) toward this extract compared to drug-sensitive CCRF-CEM cells, whereas CEM/ADR5000 cells were 2586-fold resistant to doxorubicin as control drug. Collateral sensitivity was verified by measurement of apoptotic cells by flow cytometry. The log10IC50values of 3 compounds in the extract (limonene, eucalyptol, oleic acid) did not correlate with mRNA expression of the P-glycoprotein-codingABCB1/MDR1gene and accumulation of the P-glycoprotein substrate rhodamine in the NCI panel of tumor cell lines. A microarray-based profile of 20 genes predicted resistance to doxorubicin and 7 other anticancer drugs involved in the multidrug resistance phenotype but not to limonene, eucalyptol and oleic acid. In conclusion, our results show thatLaurus nobilisseed extract is suitable to kill multidrug-resistant P-glycoprotein expressing tumor cells. [ABSTRACT FROM AUTHOR]

Background: Multidrug resistance (MDR) is a major hurdle for cancer treatment worldwide and accounts for chemotherapy failure in over 90% of patients with metastatic cancer. Evidence of the cytotoxicity of Cameroonian plants against cancer cell lines including MDR phenotypes is been intensively and progressively provided. The present work was therefore designed to evaluate the cytotoxicity of the methanol extracts of twenty-two Cameroonian medicinal plants against sensitive and MDR cancer cell lines. Methods: The methanol maceration was used to obtain the crude plant extracts whilst the cytotoxicity of the studied extracts was determined using a resazurin reduction assay. Results: A preliminary assay on leukemia CCRF-CEM cells at 40 µg/mL shows that six of the twenty plant extract were able to enhance less than 50% of the growth proliferation of CCRF-CEM cells. These include Crinum zeylanicum (32.22%), Entada abyssinica (34.67%), Elaoephorbia drupifera (35.05%), Dioscorea bulbifera (45.88%), Eremomastax speciosa (46.07%) and Polistigma thonningii (45.11%). Among these six plants, E. drupifera showed the best activity with IC50 values below or around 30 µg/mL against the nine tested cancer cell lines. The lowest IC50 value of 8.40 µg/mL was recorded with the extract of E. drupifera against MDA-MB231 breast cancer cell line. The IC50 values below 10 µg/mL were recorded with the extracts of E. drupifera against MDA-MB231 breast cancer cells, C. zeylanicum against HCT116 p53+/+ and HCT116p53-/- colon cancer cells and E. abyssinica against HCT116 p53+/+ cells. Conclusion: The results of the present study provide evidence of the cytotoxic potential of some Cameroonian medicinal plants and a baseline information for the potential use of Elaoephorbia drupifera in the treatment of sensitive and drug-resistant cancer cell lines. [ABSTRACT FROM AUTHOR]

Several flavonoid-like compounds were found to possess good antiproliferative properties. Herein, we examined the ability of four naturally occuring and biologically active flavonoids from the genus Dorstenia, gancaonin Q (1), 6-prenylapigenin (2), 6,8-diprenyleriodictyol (3), and 4-hydroxylonchocarpin ( 4), to inhibit the proliferation of a panel of fourteen cancer cell lines including leukemia and solid cancer cells, as well as AML12 normal hepatocytes. The study was extended to the analysis of cell cycle distribution, apoptosis induction, and caspase 3/7 activity and the antiangiogenic properties of the four compounds. The results of the cytotoxicity assays showed that more than 50 % inhibition of proliferation was obtained with compound 1 on all the fourteen studied cancer cell lines, with IC (50) values below 20 µg/mL. Compounds 2, 4, and 3 showed selective activity, with IC (50) values below 20 µg/mL being noted on 57.15 %, 71.42 %, and 85.71 % of the fourteen cancer cell lines, respectively. None of the compounds exhibited more than 50 % inhibition against AML12 normal hepatocytes cells at 20 µg/mL. IC (50) values below or around 4 µg/mL were recorded on 28.57 % of the tested cell lines for both compound 1 and 4 and 21.43 % for compound 3, which appeared to be the best cytotoxic compounds. This study indicates that caspase 3/7 activation is one of the modes of induction of apoptosis for compounds 1, 3, and 4 in CCRF-CEM cells. The results of the antiangiogenic assay indicated that compounds 1, 3, and 4 were also able to inhibit the growth of blood capillaries on the chorioallantoic membrane of quail eggs, the best effect being noted for compound 4 (54.1 % inhibition). The results of the present work provide evidence of the cytotoxic potential of the four studied flavonoids and supportive data for further investigations., (© Georg Thieme Verlag KG Stuttgart · New York.)