原创力文档regulation of apoptotic effects by erythrocarpine e, a cytotoxic limonoid from chisocheton erythrocarpus in hsc-4 human oral cancer cellserythrocarpine e调节凋亡影响的细胞毒性limonoid从chisocheton erythrocarpus hsc-4人类口腔癌细胞.pdfVIP
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regulation of apoptotic effects by erythrocarpine e, a cytotoxic limonoid from chisocheton erythrocarpus in hsc-4 human oral cancer cellserythrocarpine e调节凋亡影响的细胞毒性limonoid从chisocheton erythrocarpus hsc-4人类口腔癌细胞
Regulation of Apoptotic Effects by Erythrocarpine E, a
Cytotoxic Limonoid from Chisocheton erythrocarpus in
HSC-4 Human Oral Cancer Cells
1 1 2 1
Noor Hasima Nagoor *, Norliza Shah Jehan Muttiah , Chong Soon Lim , Lionel L. A. In *, Khalit
Mohammad3, Khalijah Awang2
1 Faculty of Science, Institute of Biological Science (Genetics and Molecular Biology), University Malaya, Kuala Lumpur, Malaysia, 2 Department of Chemistry, Faculty of
Science, Centre for Natural Product Research and Drug Discovery (CENAR), University Malaya, Kuala Lumpur, Malaysia, 3 Department of Pharmacy, Faculty of Medicine,
University Malaya, Kuala Lumpur, Malaysia
Abstract
The aim of this study was to determine the cytotoxic and apoptotic effects of erythrocarpine E (CEB4), a limonoid extracted
from Chisocheton erythrocarpus on human oral squamous cell carcinoma. Based on preliminary dimethyl-2-thiazolyl-2,5-
diphenyl-2H-tetrazolium bromide (MTT) assays, CEB4 treated HSC-4 cells demonstrated a cytotoxic effect and inhibited cell
proliferation in a time and dose dependent manner with an IC50 value of 4.0 61.9 mM within 24 h of treatment. CEB4 was
also found to have minimal cytotoxic effects on the normal cell line, NHBE with cell viability levels maintained above 80%
upon treatment. Annexin V-fluorescein isothiocyanate (FITC), poly-ADP ribose polymerase (PARP) cleavage and DNA
fragmentation assay results showed that CEB4 induces apoptosis mediated cell death. Western blotting results
demonstrated that the induction of apoptosis by CEB4 appeared to be mediated through regulation of the p53 signalling
pathway as there was an increase in p53 phosphorylation levels. CEB4 was also found to up-regulate the pro-apop
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