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Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions
Turmeric spice contains curcuminoids, which are polyphenolic compounds found in the Curcuma longa plant’s rhizome. This class of molecules includes curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Using prostate cancer cell lines PC3, LNCaP, DU145, and C42B, we show that curcuminoids inhibit c...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659251/ https://www.ncbi.nlm.nih.gov/pubmed/36364236 http://dx.doi.org/10.3390/molecules27217410 |
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author | Alhasawi, Mohammed Ahmed Ismail Aatif, Mohammad Muteeb, Ghazala Alam, Mir Waqas Oirdi, Mohamed El Farhan, Mohd |
author_facet | Alhasawi, Mohammed Ahmed Ismail Aatif, Mohammad Muteeb, Ghazala Alam, Mir Waqas Oirdi, Mohamed El Farhan, Mohd |
author_sort | Alhasawi, Mohammed Ahmed Ismail |
collection | PubMed |
description | Turmeric spice contains curcuminoids, which are polyphenolic compounds found in the Curcuma longa plant’s rhizome. This class of molecules includes curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Using prostate cancer cell lines PC3, LNCaP, DU145, and C42B, we show that curcuminoids inhibit cell proliferation (measured by MTT assay) and induce apoptosis-like cell death (measured by DNA/histone ELISA). A copper chelator (neocuproine) and reactive oxygen species scavengers (thiourea for hydroxyl radical, superoxide dismutase for superoxide anion, and catalase for hydrogen peroxide) significantly inhibit this reaction, thus demonstrating that intracellular copper reacts with curcuminoids in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitize normal breast epithelial cells (MCF-10A) to curcumin-mediated growth inhibition, as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters CTR1 and ATP7A in MCF-10A cells, which is attenuated by the addition of curcumin in the medium. We propose that the copper-mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of curcuminoids. |
format | Online Article Text |
id | pubmed-9659251 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96592512022-11-15 Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions Alhasawi, Mohammed Ahmed Ismail Aatif, Mohammad Muteeb, Ghazala Alam, Mir Waqas Oirdi, Mohamed El Farhan, Mohd Molecules Article Turmeric spice contains curcuminoids, which are polyphenolic compounds found in the Curcuma longa plant’s rhizome. This class of molecules includes curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Using prostate cancer cell lines PC3, LNCaP, DU145, and C42B, we show that curcuminoids inhibit cell proliferation (measured by MTT assay) and induce apoptosis-like cell death (measured by DNA/histone ELISA). A copper chelator (neocuproine) and reactive oxygen species scavengers (thiourea for hydroxyl radical, superoxide dismutase for superoxide anion, and catalase for hydrogen peroxide) significantly inhibit this reaction, thus demonstrating that intracellular copper reacts with curcuminoids in cancer cells to cause DNA damage via ROS generation. We further show that copper-supplemented media sensitize normal breast epithelial cells (MCF-10A) to curcumin-mediated growth inhibition, as determined by decreased cell proliferation. Copper supplementation results in increased expression of copper transporters CTR1 and ATP7A in MCF-10A cells, which is attenuated by the addition of curcumin in the medium. We propose that the copper-mediated, ROS-induced mechanism of selective cell death of cancer cells may in part explain the anticancer effects of curcuminoids. MDPI 2022-11-01 /pmc/articles/PMC9659251/ /pubmed/36364236 http://dx.doi.org/10.3390/molecules27217410 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Alhasawi, Mohammed Ahmed Ismail Aatif, Mohammad Muteeb, Ghazala Alam, Mir Waqas Oirdi, Mohamed El Farhan, Mohd Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions |
title | Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions |
title_full | Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions |
title_fullStr | Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions |
title_full_unstemmed | Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions |
title_short | Curcumin and Its Derivatives Induce Apoptosis in Human Cancer Cells by Mobilizing and Redox Cycling Genomic Copper Ions |
title_sort | curcumin and its derivatives induce apoptosis in human cancer cells by mobilizing and redox cycling genomic copper ions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659251/ https://www.ncbi.nlm.nih.gov/pubmed/36364236 http://dx.doi.org/10.3390/molecules27217410 |
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