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Cytotoxic Profiling of Plant Secondary Metabolites on P53 Variant Human Colon Carcinoma Cell Lines

Chemoprevention strategies employ the use of compounds to inhibit the initiation, promotion, and progression phases of carcinogenesis. The successful chemopreventative candidate must therefore (1) selectively inhibit growth of transformed cells and (2) be administered on a frequent basis to confer m...

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Autores principales: Dusan, Vukmirovic, Dave, Rollo, Colin, Seymour, Carmel, Mothersill
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751922/
https://www.ncbi.nlm.nih.gov/pubmed/29308058
http://dx.doi.org/10.1177/1559325817748121
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author Dusan, Vukmirovic
Dave, Rollo
Colin, Seymour
Carmel, Mothersill
author_facet Dusan, Vukmirovic
Dave, Rollo
Colin, Seymour
Carmel, Mothersill
author_sort Dusan, Vukmirovic
collection PubMed
description Chemoprevention strategies employ the use of compounds to inhibit the initiation, promotion, and progression phases of carcinogenesis. The successful chemopreventative candidate must therefore (1) selectively inhibit growth of transformed cells and (2) be administered on a frequent basis to confer maximal protection. Phytochemicals are a subclass of bioactive plant secondary metabolites that exhibit antioxidative, anticarcinogenic, and anti-inflammatory properties contributing to proper cell function. To assess the effectiveness of these compounds warrants an understanding of their cytotoxic mode of action. In this study, p53 variant human colon carcinoma cell lines were chronically exposed to varying concentrations of the phytochemicals—curcumin, andrographolide, and d-limonene—to determine the role of p53-induced cytotoxicity, with p53-mutant and p53-deficient cell lines representing precancerous lesions. Cytotoxicity was assessed using clonogenic assays and macroscopic colony counts were used to quantify cell survival. The results demonstrate that each phytochemical exhibits selective cytotoxicity toward nonfunctional p53 cell lines, suggesting a p53-mediated role in inhibition of cell clonogenicity and potential chemopreventative properties. Although each compound displays this described effect, only the d-limonene demonstrates considerable chemoprotection, suggesting it might have practical implications in vivo.
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spelling pubmed-57519222018-01-05 Cytotoxic Profiling of Plant Secondary Metabolites on P53 Variant Human Colon Carcinoma Cell Lines Dusan, Vukmirovic Dave, Rollo Colin, Seymour Carmel, Mothersill Dose Response Original Article Chemoprevention strategies employ the use of compounds to inhibit the initiation, promotion, and progression phases of carcinogenesis. The successful chemopreventative candidate must therefore (1) selectively inhibit growth of transformed cells and (2) be administered on a frequent basis to confer maximal protection. Phytochemicals are a subclass of bioactive plant secondary metabolites that exhibit antioxidative, anticarcinogenic, and anti-inflammatory properties contributing to proper cell function. To assess the effectiveness of these compounds warrants an understanding of their cytotoxic mode of action. In this study, p53 variant human colon carcinoma cell lines were chronically exposed to varying concentrations of the phytochemicals—curcumin, andrographolide, and d-limonene—to determine the role of p53-induced cytotoxicity, with p53-mutant and p53-deficient cell lines representing precancerous lesions. Cytotoxicity was assessed using clonogenic assays and macroscopic colony counts were used to quantify cell survival. The results demonstrate that each phytochemical exhibits selective cytotoxicity toward nonfunctional p53 cell lines, suggesting a p53-mediated role in inhibition of cell clonogenicity and potential chemopreventative properties. Although each compound displays this described effect, only the d-limonene demonstrates considerable chemoprotection, suggesting it might have practical implications in vivo. SAGE Publications 2017-12-21 /pmc/articles/PMC5751922/ /pubmed/29308058 http://dx.doi.org/10.1177/1559325817748121 Text en © The Author(s) 2017 http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Dusan, Vukmirovic
Dave, Rollo
Colin, Seymour
Carmel, Mothersill
Cytotoxic Profiling of Plant Secondary Metabolites on P53 Variant Human Colon Carcinoma Cell Lines
title Cytotoxic Profiling of Plant Secondary Metabolites on P53 Variant Human Colon Carcinoma Cell Lines
title_full Cytotoxic Profiling of Plant Secondary Metabolites on P53 Variant Human Colon Carcinoma Cell Lines
title_fullStr Cytotoxic Profiling of Plant Secondary Metabolites on P53 Variant Human Colon Carcinoma Cell Lines
title_full_unstemmed Cytotoxic Profiling of Plant Secondary Metabolites on P53 Variant Human Colon Carcinoma Cell Lines
title_short Cytotoxic Profiling of Plant Secondary Metabolites on P53 Variant Human Colon Carcinoma Cell Lines
title_sort cytotoxic profiling of plant secondary metabolites on p53 variant human colon carcinoma cell lines
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751922/
https://www.ncbi.nlm.nih.gov/pubmed/29308058
http://dx.doi.org/10.1177/1559325817748121
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