RSS-Feed abonnieren
DOI: 10.1055/s-0031-1280023
© Georg Thieme Verlag KG Stuttgart · New York
Cytotoxicity and Mode of Action of Four Naturally Occuring Flavonoids from the Genus Dorstenia: Gancaonin Q, 4-Hydroxylonchocarpin, 6-Prenylapigenin, and 6,8-Diprenyleriodictyol
Publikationsverlauf
received March 22, 2011
revised May 26, 2011
accepted June 1, 2011
Publikationsdatum:
28. Juli 2011 (online)
![](https://www.thieme-connect.de/media/plantamedica/201118/lookinside/thumbnails/10.1055-s-0031-1280023-1.jpg)
Abstract
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 IC50 values below 20 µg/mL. Compounds 2, 4, and 3 showed selective activity, with IC50 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. IC50 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.
Key words
flavonoids - cytotoxicity - apoptosis - caspase - angiogenesis - Dorstenia - Moraceae
References
- 1 Noonan D M, Benelli R, Albini A. Angiogenesis and cancer prevention: a vision. Rec Res Cancer Res. 2007; 174 219-224
- 2 Freitas S, Costa S, Azevedo C, Carvalho G, Freire S, Barbosa P, Velozo E, Schaer R, Tardy M, Meyer R, Nascimento I. Flavonoids inhibit angiogenic cytokine production by human glioma cells. Phytother Res. 2011; 25 916-921
- 3 Deeb D, Gao X, Jiang H, Arbab A S, Dulchavsky S A, Gautam S C. Growth inhibitory and apoptosis-inducing effects of xanthohumol, a prenylated chalone present in hops, in human prostate cancer cells. Anticancer Res. 2010; 30 3333-3339
- 4 Jaramillo S, Lopez S, Varela L M, Rodriguez-Arcos R, Jimenez A, Abia R, Guillen R, Muriana F J. The flavonol isorhamnetin exhibits cytotoxic effects on human colon cancer cells. J Agric Food Chem. 2010; 58 10869-10875
- 5 Fang N, Casida J E. New bioactive flavonoids and stilbenes in cubé resin insecticide. J Nat Prod. 1999; 62 205-210
- 6 Seo E K, Silva G L, Chai H B, Chagwedera T E, Farnsworth N R, Cordell G A, Pezzuto J M, Kinghorn A D. Cytotoxic prenylated flavanones from Monotes engleri. Phytochemistry. 1997; 45 509-515
- 7 Kuete V, Simo I K, Ngameni B, Bigoga J D, Watchueng J, Kapguep R N, Etoa F X, Tchaleu B N, Beng V P. Antimicrobial activity of the methanolic extract, fractions and four flavonoids from the twigs of Dorstenia angusticornis Engl. (Moraceae). J Ethnopharmacol. 2007; 112 271-277
- 8 Arung E T, Shimizu K, Kondo R. Inhibitory effect of isoprenoid-substituted flavonoids isolated from Artocarpus heterophyllus on melanin biosynthesis. Planta Med. 2006; 72 847-850
- 9 Omisore N O A, Adewunmi C A, Iwalewa E O, Ngadjui B T, Adenowo T K, Abegaz B M, Ojewole J A, Watchueng J. Antitrichomonal and antioxidant activities of Dorstenia barteri and Dorstenia convexa. Braz J Med Biol Res. 2005; 38 1087-1094
- 10 Mbaveng A T, Ngameni B, Kuete V, Konga S I, Ambassa T, Roy R, Abegaz B M, Etoa F X, Ngadjui B T, Beng V P. Antimicrobial activity of the crude extracts and five flavonoids from the twigs of Dorstenia barteri (Moraceae). J Ethnopharmacol. 2008; 116 483-489
- 11 Kuete V, Ngameni B, Mbaveng A T, Ngadjui B, Marion Meyer J J, Lall N. Evaluation of flavonoids from Dorstenia barteri for their antimycobacterial, antigonorrheal and anti-reverse transcriptase activities. Acta Trop. 2010; 116 100-104
- 12 Ngadjui B T, Dongo E, Abegaz B M, Fotso S, Tamboue H. Dinklagins A, B and C: three prenylated flavonoids and other constituents from the twigs of Dorstenia dinklagei. Phytochemistry. 2002; 61 99-104
- 13 Ngadjui B T, Kouam S F, Dongo E, Kapche G W, Abegaz B M. Prenylated flavonoids from the aerial parts of Dorstenia mannii. Phytochemistry. 2000; 55 915-919
- 14 O'Brien J, Wilson I, Orton T, Pognan F. Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem. 2000; 267 5421-5426
- 15 Joshi S C, Verma A R, Mathela C S. Antioxidant and antibacterial activities of the leaf essential oils of Himalayan Lauraceae species. Food Chem Toxicol. 2010; 48 37-40
- 16 Wittmann J, Kugler W, Kaltner H. Cultivation of the early quail embryo: induction of embryogenesis under in vitro conditions. J Exp Zool Suppl. 1987; 1 325-328
- 17 D'Arcy P F, Howard E M. A new anti-inflammatory test, utilizing the chorioallantoic membrane of the chick embryo. Br J Pharmacol Chemother. 1967; 29 378-387
- 18 Marchesan M, Paper D H, Hose S, Franz G. Investigations of the anti-inflammatory activity of liquid extracts of Plantago lanceolata L. Phytother Res. 1998; 12 S33-S34
- 19 Kuete V, Youns M, Krusche B, Voukeng I, Fankam A G, Tankeo S, Lacmata S, Efferth T. Cytotoxicity of some Cameroonian spices and selected medicinal plant extracts. J Ethnopharmacol. 2011; 134 803
- 20 Boik J. Natural compounds in cancer therapy. Princeton, MN, USA: Oregon Medical Press; 2001
- 21 Brahemi G, Kona F R, Fiasella A, Buac D, Soukupov J, Brancale A, Burger A M, Westwell A D. Exploring the structural requirements for inhibition of the ubiquitin E3 ligase breast cancer associated protein 2 (BCA2) as a treatment for breast cancer. J Med Chem. 2010; 53 2757-2765
Prof. Dr. Thomas Efferth
Department of Pharmaceutical Biology
Institute of Pharmacy and Biochemistry
University of Mainz
Staudinger Weg 5
55128 Mainz
Germany
Telefon: +49 6 13 13 92 57 51
Fax: +49 6 13 13 92 37 52
eMail: efferth@uni-mainz.de