Abstract
Malignancies constitute a global health concern and chemotherapy remains the main mode of treatment. The present study was designed to evaluate the cytotoxicity of 8 compounds from Desbordesia glaucescens namely lanosta-7,24-dien-3-one (1), friedelanone (2), friedelanol (3), 3,3′-di-O-methylellagic acid (4), 3,3′,4′-tri-O-methylellagic acid (5), ellagic acid (6), 3′,4′-di-O-methylellagic acid 4-O-β-d-glucopyranoside (7) and 3,3′-di-O-methylellagic acid 4′-O-β-d-xylopyranoside (8) against 4 human carcinoma cell lines and normal CRL2120 fibroblasts. The neutral red uptake (NRU) assay was used for cytotoxicity testing. Caspase-Glo assay, cell cycle analysis, measurements of mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were used to evaluate apoptosis induction. Compounds 4 and 6 as well as doxorubicin had IC50 values below 45μM in the four tested cancer cell lines meanwhile other compounds displayed selective activity. The IC50 values ranged from 11.23μM (towards breast adenocarcinoma MCF-7 cells) to 44.65μM (colon carcinoma Caco-2 cells) for 4, from 14.07μM (towards MCF-7 cells) to 77.73μM (Caco-2 cells) for 6 and from 0.07μM (towards SPC212 cells) to 1.01μM (A549 cells) for doxorubicin. Compound 4 induced apoptosis in MCF-7 cells mediated by MMP loss. The constituents of Desbordesia glaucescens and especially ellagic acid (6) and its derivative 4 are potential cytotoxic compounds that deserve more investigations towards developing novel antiproliferative drugs against human carcinoma.
Highlights
Cancer is one of the five leading causes of death globally and according to the International Agency for Research on Cancer (IARC) for 2012, 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide (Bray et al, 2013; Ferlay et al, 2013)
Compounds isolated from the stem of Desbordesia glaucescens were elucidated using physical and NMR data and comparison with literature (Data available in supporting information)
The cytotoxicity of the 8 isolated compounds and doxorubicin was determined by the neutral red uptake (NRU) uptake assay and the recorded IC50 values are Growth Growth Growth
Summary
Cancer is one of the five leading causes of death globally and according to the International Agency for Research on Cancer (IARC) for 2012, 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide (Bray et al, 2013; Ferlay et al, 2013). Drug discovery from African plants is of relevant interest because Africa hosts 57,704 species of the world's flora (Fadeyi et al, 2013). Evidence of the anticancer activity of several plants and compounds from African flora was documented (Kuete and Efferth, 2015). In our continuous search of cytotoxic molecules to combat malignant diseases, the present study was designed to investigate the antiproliferative potential of compounds isolated from Desbordesiaglaucescens (Engl.) Tiegh. Desbordesiaglaucescens is found around forest zones in South Nigeria, West Cameroon, Gabon, Congo, and Angola (Letouzey, 1982). In Congo, the seeds are used as a food additive while bark-decoctions are taken to attenuate stomach-ache, and as an aphrodisiac. Previous phytochemical studies on D. glaucescens reported the isolation of ellagic acid derivatives and triterpenes (DongmoMafodong et al, 2015)
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