ABSTRACT
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-ß-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-ß-sitosterol and suggest its potential anti-cancer use particularly on breast adenocarcinoma cells.
ABSTRACT
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: IC50, 0.9, 21.7, and >50.0 µM, respectively, 2: IC50 >50.0, 15.7, and 12.4 µM, respectively).
Subject(s)
Alkaloids/chemistry , Annonaceae/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Aporphines/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Aporphines/isolation & purification , Aporphines/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Magnetic Resonance Spectroscopy , Molecular Conformation , Plant Bark/chemistry , Plant Stems/chemistryABSTRACT
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.
Subject(s)
Limonins/isolation & purification , Meliaceae/chemistry , Animals , Crystallography, X-Ray , Dose-Response Relationship, Drug , Limonins/chemistry , Limonins/pharmacology , Lipopolysaccharides/pharmacology , Malaysia , Mice , Models, Molecular , Molecular Structure , Nitric Oxide/antagonists & inhibitors , Nuclear Magnetic Resonance, Biomolecular , Plant Bark/chemistry , omega-N-Methylarginine/pharmacologyABSTRACT
Both independent mol-ecules in the asymmetric unit of the title compound, C(11)H(10)O(4), are almost planar (r.m.s. deviations = 0.011 and 0.033â Å). In both mol-ecules, the hy-droxy group is intra-molecularly hydrogen bonded to the ketonic O atom. The independent mol-ecules are stacked alternately along the a axis, with the centroids of their chromene ring separated by distances of 4.490â (1) and 3.621â (1)â Å.
ABSTRACT
The title limonoid 14-de-oxyxyloccensin K, C(27)H(34)O(7), isolated from Chisocheton ceramicus (Meliaceae), features an oxygen linkage between carbon-3 and carbon-8 along with a tetra-hydro-furyl sub-unit. The six-membered rings adopt chair configurations and the tetra-hydro-furyl sub-unit has an envelope shape.
ABSTRACT
The asymmetric unit of the title compound, C(29)H(50)O(2), contains two mol-ecules; one mol-ecule is linked to the other by two O-Hâ¯O hydrogen bonds, whereas only one of the hydr-oxy groups of the second mol-ecule is involved in hydrogen bonding. This gives rise to a chain that runs along the a axis of the monoclinic unit cell.