Acridone alkaloids from the stem bark of Citrus aurantium display selective cytotoxicity against breast, liver, lung and prostate human carcinoma cells. (5th December 2018)

• Record Type: Journal Article
• Authors: Segun, Peter A.; Ismail, Fyaz M.D.; Ogbole, Omonike O.; Nahar, Lutfun; Evans, Andrew R.; Ajaiyeoba, Edith O.; Sarker, Satyajit D.
• Is Part Of: Journal of ethnopharmacology. Volume 227(2018)
• Page Start: 131
• Page End: 138
• Publication Date: 2018-12-05
• Subjects: A549 human lung adenocarcinoma -- ANOVA one-way analysis of variance -- ATCC American type culture collection -- CDCl3 chloroform -- DMSO dimethyl sulfoxide -- ECACC European collection of authenticated cell cultures -- HepG2 human liver adenocarcinoma -- HPLC high performance liquid chromatography -- HR-EI-MS high resolution electrospray ionization mass spectrometry -- IC50 50% inhibitory concentration -- MCF7 human breast adenocarcinoma -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium -- NCI national cancer institute -- NMR nuclear magnetic resonance -- OD optical density -- PBS phosphate buffered-saline -- PC3 human prostate adenocarcinoma -- PNT2 normal human immortalised prostate cell line -- SI selectivity index -- SS stock solution -- VLC vacuum liquid chromatography -- MeOH methanol -- DCM dichloromethane -- n-hex n-hexane -- SEM standard error of mean -- COSY correlated spectroscopy -- HMBC heteronuclear multiple bond correlation -- NOESY nuclear Overhauser effect spectroscopy -- DEPTQ distortionless enhancement by polarisation transfer -- FBS foetal bovine serum -- FHI forest herbarium Ibadan -- IR infra-red spectroscopy -- m/z mass to charge ratio -- WHO world health organisation -- Hz hertz -- CC column chromatography -- HSQC homonuclear single quantum correlation -- UV ultraviolet spectroscopy; Citrus aurantium -- Rutaceae -- Acridone alkaloids -- Cytotoxicity, MTT assay; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2018.08.039
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Citrus aurantium L. (Rutaceae) is used, either singly or as a part of a polyherbal preparation, in Nigerian traditional medicine for the management of cancer and inflammatory diseases. Currently, there is a dearth of knowledge demonstrating its anticancer potential. Aim of the study: This study was carried out to determine the in vitro cytotoxicity of the crude extract of the stem bark of C. aurantium, identify and isolate the bioactive constituents and to establish the cytotoxicity of such constituents. Materials and methods: The powdered bark of C. aurantium was extracted by MeOH at room temperature (25–34 °C) and the crude extract was partitioned successively, with n -hexane, dichloromethane and methanol. Amongst the fractions, the DCM fraction was the most active and compounds were isolated from this fraction using a combination of chromatographic techniques. The structures of the isolated compounds were elucidated by spectroscopic means (MS, 1D and 2D NMR). The cytotoxicity of the extract, and the isolated compounds were evaluated by the MTT assay against four human cancer cell lines: A549 (lung), HepG2 (liver), MCF7 (breast) and PC3 (prostate). The selectivity of the isolated compounds was assessed using the normal human prostate epithelium cells (PNT2). Results and discussion: Of the three plant fractions, the DCM fraction showed significant cytotoxicity, with its highest activity against A549 cells (IC50 = 3.88 µg/mL) and the least activity on HepG2 cells (IC50 = 5.73 µg/mL). Six acridone alkaloids, citrusinine-I (1 ), citracridone-I (2 ), 5-hydroxynoracronycine (3 ), natsucitrine-I (4 ), glycofolinine (5 ) and citracridone-III (6 ), were isolated from the DCM fraction of C. aurantium. The isolated compounds demonstrated potent to moderate cytotoxicity (IC50 = 12.65–50.74 µM) against the cancer cells under investigation. It is noteworthy that the compounds exerted cytotoxicity at least four times more selective towards the carcinoma cells than the PNT2 cells. Conclusion: The results obtained from this study have provided some evidence for the ethnomedicinal use of C. aurantium against cancer and the acridone alkaloids present in its stem bark, have appeared to be responsible for the anticancer effects. Graphical abstract: