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PASS-predicted Vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells-an in vitro study

BACKGROUND: Hepatocellular carcinoma is a common type of tumour worldwide with a high mortality rate and with low response to current cytotoxic and chemotherapeutic drugs. The prediction of activity spectra for the substances (PASS) software, which predicted that more than 300 pharmacological effect...

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Autores principales: Kadir, Farkaad A, Kassim, Normadiah M, Abdulla, Mahmood A, Yehye, Wageeh A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235047/
https://www.ncbi.nlm.nih.gov/pubmed/24305067
http://dx.doi.org/10.1186/1472-6882-13-343
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author Kadir, Farkaad A
Kassim, Normadiah M
Abdulla, Mahmood A
Yehye, Wageeh A
author_facet Kadir, Farkaad A
Kassim, Normadiah M
Abdulla, Mahmood A
Yehye, Wageeh A
author_sort Kadir, Farkaad A
collection PubMed
description BACKGROUND: Hepatocellular carcinoma is a common type of tumour worldwide with a high mortality rate and with low response to current cytotoxic and chemotherapeutic drugs. The prediction of activity spectra for the substances (PASS) software, which predicted that more than 300 pharmacological effects, biological and biochemical mechanisms based on the structural formula of the substance was efficiently used in this study to reveal new multitalented actions for Vitex negundo (VN) constituents. METHODS: Experimental studies based on antioxidant and antiproliferative assays verified the predictions obtained by the PASS-predicted design strategy. Antioxidant activity of VN extract was studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and Ferric reducing or antioxidant power (FRAP) assays. The antiproliferative activity of VN extract against WRL68 and HepG2 was investigated based on methylthiazol tetrazolium (MTT) spectrophotometric assay. RESULTS: VN extract showed 79.43% inhibition of DPPH stable radical with IC(50) 13.31 ± 0.18 μg/ml. This inhibition was too closed to butylated hydroxyl toluene (BHT) 82.53% (IC(50)13.8 ± 0.14) and gallic acid 89.51% (IC(50) 3.1 ± 0.08). VN extract exhibited the strongest free radical scavenging power compared with two commercial antioxidants, BHT and ascorbic acid. VN increased the activities of antioxidant enzymes in normal embryonic liver cells (WRL68) including, superoxide dismutase (SOD) and glutathione peroxidase (GPX) compared with to H(2)O(2) group. The ethanolic extract of VN showed cytotoxicity to HepG2 cells in a dose and time-dependent manner with IC(50) 66.46 μg/ml, 57.36 μg/ml and 65.12 μg/ml at 24, 48, and 72-hours incubation respectively, with no sensitivity in WRL68 cells. This was associated with significant elevation in lactate dehydrogenase (LDH) release in HepG2 cells. In addition, the activation of caspase-3 enzyme suggesting that the observed cytotoxicity was mediated via an intrinsic apoptosis pathway. CONCLUSIONS: PASS-predicted plant activity could efficiently help in selecting a promising pharmaceutical leads with high accuracy and required antioxidant and antiproliferative properties. This is the first report on PASS-predicted VN activity.
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spelling pubmed-42350472014-11-19 PASS-predicted Vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells-an in vitro study Kadir, Farkaad A Kassim, Normadiah M Abdulla, Mahmood A Yehye, Wageeh A BMC Complement Altern Med Research Article BACKGROUND: Hepatocellular carcinoma is a common type of tumour worldwide with a high mortality rate and with low response to current cytotoxic and chemotherapeutic drugs. The prediction of activity spectra for the substances (PASS) software, which predicted that more than 300 pharmacological effects, biological and biochemical mechanisms based on the structural formula of the substance was efficiently used in this study to reveal new multitalented actions for Vitex negundo (VN) constituents. METHODS: Experimental studies based on antioxidant and antiproliferative assays verified the predictions obtained by the PASS-predicted design strategy. Antioxidant activity of VN extract was studied using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and Ferric reducing or antioxidant power (FRAP) assays. The antiproliferative activity of VN extract against WRL68 and HepG2 was investigated based on methylthiazol tetrazolium (MTT) spectrophotometric assay. RESULTS: VN extract showed 79.43% inhibition of DPPH stable radical with IC(50) 13.31 ± 0.18 μg/ml. This inhibition was too closed to butylated hydroxyl toluene (BHT) 82.53% (IC(50)13.8 ± 0.14) and gallic acid 89.51% (IC(50) 3.1 ± 0.08). VN extract exhibited the strongest free radical scavenging power compared with two commercial antioxidants, BHT and ascorbic acid. VN increased the activities of antioxidant enzymes in normal embryonic liver cells (WRL68) including, superoxide dismutase (SOD) and glutathione peroxidase (GPX) compared with to H(2)O(2) group. The ethanolic extract of VN showed cytotoxicity to HepG2 cells in a dose and time-dependent manner with IC(50) 66.46 μg/ml, 57.36 μg/ml and 65.12 μg/ml at 24, 48, and 72-hours incubation respectively, with no sensitivity in WRL68 cells. This was associated with significant elevation in lactate dehydrogenase (LDH) release in HepG2 cells. In addition, the activation of caspase-3 enzyme suggesting that the observed cytotoxicity was mediated via an intrinsic apoptosis pathway. CONCLUSIONS: PASS-predicted plant activity could efficiently help in selecting a promising pharmaceutical leads with high accuracy and required antioxidant and antiproliferative properties. This is the first report on PASS-predicted VN activity. BioMed Central 2013-12-04 /pmc/articles/PMC4235047/ /pubmed/24305067 http://dx.doi.org/10.1186/1472-6882-13-343 Text en Copyright © 2013 Kadir et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kadir, Farkaad A
Kassim, Normadiah M
Abdulla, Mahmood A
Yehye, Wageeh A
PASS-predicted Vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells-an in vitro study
title PASS-predicted Vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells-an in vitro study
title_full PASS-predicted Vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells-an in vitro study
title_fullStr PASS-predicted Vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells-an in vitro study
title_full_unstemmed PASS-predicted Vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells-an in vitro study
title_short PASS-predicted Vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells-an in vitro study
title_sort pass-predicted vitex negundo activity: antioxidant and antiproliferative properties on human hepatoma cells-an in vitro study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235047/
https://www.ncbi.nlm.nih.gov/pubmed/24305067
http://dx.doi.org/10.1186/1472-6882-13-343
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