Search

Objectives To evaluate anti-proliferative as well as apoptotic activities of compounds identified in chloroform extract of Juglans regia leaves, on human breast and oral cancer cell lines ( MCF-7 and BHY). Materials and methods Column chromatography, MTT assay, flowcytometry and western blotting have all been used in the study. Results Bioassay-guided fractionation of chloroform extract of J. regia afforded isolation of 5-hydroxy-3,7,4′-trimethoxyflavone [ 1], lupeol [ 2], daucosterol [ 3], 4-hydroxy-α -tetralone [ 4], β-sitosterol [ 5], 5,7- dihydroxy-3,4′-dimethoxyflavone [ 6] and regiolone [ 7]. Structures of the compounds were established on the basis of spectroscopic analyses [Nuclear magnetic resonance (NMR) and mass]. All compounds inhibited proliferation of MCF-7 (human breast adenocarcinoma) and BHY (human oral squamous carcinoma) cells in a concentration-dependent manner. Compounds 6 and 7 had potent cytotoxic effects on both MCF-7 and BHY cells ( IC50 21-51 μ m), yet were not toxic to normal cells. MCF-7 growth inhibition was attributed to apoptosis; population of apoptotic cells increased from 1.12% in controls to 5.64 and 8.1% after 48-h treatment with compounds 6 and 7, indicating their potential at inducing early and late apoptosis. The caspase cascade was not activated, as indicated by only insignificant cleavage of caspase-3. Conclusions Our results suggest that compounds 6 and 7 can induce apoptosis in MCF-7 cells through the caspase-3 independent pathway. [ABSTRACT FROM AUTHOR]