In continuation of our interest towards the elucidation of apoptotic pathways of cytotoxic phytocompounds, we have embarked upon a study on the anticancer effects of 7α-hydroxy-β-sitosterol (CT1), a rare natural phytosterol oxide isolated from Chisocheton tomentosus. CT1 was found to be cytotoxic on three different human tumor cell lines with minimal effects on normal cell controls, where cell viability levels were maintained ≥80% upon treatment. Our results showed that cell death in MCF-7 breast tumor cells was achieved through the induction of apoptosis via downregulation of the ERK1/2 signaling pathway. CT1 was also found to increase proapoptotic Bax protein levels, while decreasing anti-apoptotic Bcl-2 protein levels, suggesting the involvement of the intrinsic pathway. Reduced levels of initiator procaspase-9 and executioner procaspase-3 were also observed following CT1 exposure, confirming the involvement of cytochrome c-mediated apoptosis via the mitochondrial pathway. These results demonstrated the cytotoxic and apoptotic ability of 7α-hydroxy-β-sitosterol and suggest its potential anti-cancer use particularly on breast adenocarcinoma cells.
Three new limonoids, chisomicines A-C (1-3), have been isolated from the bark of Chisocheton ceramicus. Their structures were determined by 2D NMR, CD spectroscopic methods, and X-ray analysis. Chisomicine A (1) exhibited NO production inhibitory activity in J774.1 cells stimulated by LPS dose-dependently at high cell viability.
Pseuduvarines A (1) and B (2), two new dioxoaporphine alkaloids with an amino moiety, were isolated from the stem bark of Pseuduvaria rugosa and their structures were elucidated by combination of 2D-NMR spectroscopic analysis. Pseuduvarines A (1) and B (2) showed cytotoxicity against MCF7, HepG2, and HL-60 (1: IC 50 , 0.9, 21.7, and Ͼ50.0 m mM, respectively, 2: IC 50 Ͼ50.0, 15.7, and 12.4 m mM, respectively).
Four steroids have been isolated from dichloromethane extract of Chisocheton tomentosus (Meliaceace), they were; 7α-hydroxy-β-sitosterol 1, stigmasta-4,6-diene-3-one 2, stigmasterol 3 and sitosterol 4. 7α-Hydroxy-β-sitosterol 1 was isolated as a colourless crystal and this compound was a new compound in crystal structure. The isolation and purification of the compounds were achieved by using column and PTL chromatographic techniques. The compounds were identified by spectroscopic techniques such as UV, IR, MS, 1D, and 2D NMR. In addition; 7 α-hydroxy-β-sitosterol was also identified by X-Ray diffraction technique.
The title limonoid 14-deoxyxyloccensin K, C27H34O7, isolated from Chisocheton ceramicus (Meliaceae), features an oxygen linkage between carbon-3 and carbon-8 along with a tetrahydrofuryl sub-unit. The six-membered rings adopt chair configurations and the tetrahydrofuryl sub-unit has an envelope shape.
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