Cytotoxicity of botanicals and isolated phytochemicals from Araliopsis soyauxii Engl. (Rutaceae) towards a panel of human cancer cells

• Published in: Journal of ethnopharmacology 2021-03, Vol.267, p.113535, Article 113535
• Main Authors: Mbaveng, Armelle T., Noulala, Cédric G.T., Samba, Anne R.M., Tankeo, Simplice B., Fotso, Ghislain W., Happi, Emmanuel N., Ngadjui, Bonaventure T., Beng, Veronique P., Kuete, Victor, Efferth, Thomas
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - metabolism; Araliopsis soyauxii; Benzoxepins - pharmacology; Cell Cycle Checkpoints - drug effects; Cytotoxicity; Dose-Response Relationship, Drug; HCT116 Cells; Hep G2 Cells; Humans; Inhibitory Concentration 50; Kihadanin B; Limonins - pharmacology; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Multidrug resistance; Neoplasms - drug therapy; Neoplasms - pathology; Oxidative Stress - drug effects; Phytochemicals - isolation & purification; Phytochemicals - pharmacology; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Reactive Oxygen Species - metabolism; Rutaceae; Rutaceae - chemistry; Signal Transduction
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2020.113535

Araliopsis soyauxii Engl. (Rutaceae) is a Cameroonian medicinal plant traditionally used to treat lung diseases, malaria, and gonorrhea. It has been demonstrated that infectious disease contribute to about 20% of all human tumours. (1) To perform a phytochemical investigation of the dichloromethane-methanol 1:1 extracts of the bark (ASB), roots (ASR), and leaves (ASL) from Araliopsis soyauxii; (2) to evaluate the cytotoxicity of extracts and isolated compounds; (3) to determine the mode of induction of apoptosis of ASB and kihadanin B (12). Fourteen constituents of the crude extracts were isolated by column chromatography, while spectroscopic techniques were used for structural elucidation. The resazurin reduction assay (RRA) was applied to determine the cytotoxicity of samples towards a panel of 9 cancer cell lines. For caspases activity, the Caspase-Glo assay was used; flow cytometry was applied to investigate the cell cycle distribution (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP; JC-1 staining), and the reactive oxygen species (ROS; H2DCFH-DA staining). Phytochemical investigations of botanicals (ASB, ASR, and ASL) led to the isolation of 14 compounds. Extract ASB, obacunone (11), kihadanin B (12) as well as doxorubicin (control drug) revealed cytotoxicity towards the 9 cancer cell lines tested. The IC50 values ranged from 11.11 μg/mL (against CCRF-CEM leukemia cells) to 28.18 μg/mL (against HCT116 p53+/+ colon adenocarcinoma cells) for ASB; from 28.25 μM (against MDA-MB-231-pcDNA breast adenocarcinoma cells) to 65.13 μM (against HepG2 hepatocarcinoma cells) for compound 11, and from 5.77 μM (against CCRF-CEM cells) to 43.56 μM (against U87.MGΔEGFR glioblastoma cells) for compound 12. ASB and compound 12 induced apoptosis in CCRF-CEM cells. ASB induced the apoptotic process mediated by MMP alteration and enhanced ROS production, while compound 12 induced apoptosis by caspases activation, MMP alteration, and enhanced ROS production. This study demonstrated that Araliopsis soyauxii is a potential source of cytotoxic phytochemicals such as kihadanin B and that ASB and compound 12. Extract and compounds will be explored further to develop anticancer drugs. [Display omitted] •The cytotoxicity of Araliopsis soyauxii Engl. (Rutaceae) extracts, and compounds was evaluated.•Extract ASB, obacunone and kihadanin B revealed cytotoxicity towards the 9 cancer cell lines tested.•ASB and kihadanin B induced apoptosis in CCRF