ABSTRACT
New clerodane diterpenes, 12-epi-megalocarpodolide D (2) and an epimeric mixture of crotonolins A (3) and B (4), were isolated from the bark of Croton oligandrus following a bioassay-guided isolation protocol. Known compounds, megalocarpodolide D (1), 12-epi-crotocorylifuran (5), cluytyl-ferulate (6), hexacosanoyl- ferulate (7), vanillin (8), acetyl-aleuritolic acid (9) and lupeol (10), were also isolated. The structures of the isolated compounds (1-10) were elucidated by spectroscopic means. The cytotoxicity of compounds 1-10 was assessed against A549, MCF7, PC3 and PNT2 cell lines using the MTT assay. Compounds 1 and 2 showed moderate levels of activity against both A549 and MCF7 cells with 1 being the most active with IC50 values of 63.8 ± 13.8 and 136.2 ± 22.7 µM against A549 and MCF7 cells, respectively. The epimeric mixture of 3 and 4 was moderately active against A549 and PC3 cells (IC50 = 128.6 ± 31.0 and 111.2 ± 2.9 µM, respectively).
Subject(s)
Antineoplastic Agents, Phytogenic/chemistry , Croton/chemistry , Cytotoxins/chemistry , Diterpenes, Clerodane/chemistry , Furans/chemistry , Pentacyclic Triterpenes/chemistry , Plant Bark/chemistry , A549 Cells , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cytotoxins/isolation & purification , Cytotoxins/pharmacology , Diterpenes, Clerodane/isolation & purification , Diterpenes, Clerodane/pharmacology , Furans/isolation & purification , Furans/pharmacology , Humans , Inhibitory Concentration 50 , MCF-7 Cells , Molecular Structure , Pentacyclic Triterpenes/isolation & purification , Pentacyclic Triterpenes/pharmacology , Plant Extracts/chemistryABSTRACT
BACKGROUND: Recent studies proposed GLUT12 to be a major glucose transporter involved in the glycolytic metabolism of cancer cells. METHODS: GLUT12 expression was determined by immunohistochemistry in a selection of cancer cell lines and a tumour spheroid model. RESULTS: GLUT12 expression was high in A549 and RH-36; low in HT29; and absent in NB-EB cancer cell lines. GLUT12 expression was located in the necrotic centre of HT29 spheroids, which is characterised by anaerobic metabolism. CONCLUSION: The data supports the involvement of GLUT12 in the glycolytic metabolism of cancer cells and therefore, its potential as a novel therapeutic target for cancer treatment.
