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Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells

Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitum...

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Autores principales: Bhardwaj, Monika, Cho, Hee Jun, Paul, Souren, Jakhar, Rekha, Khan, Imran, Lee, Seon-Jin, Kim, Bo-Yeon, Krishnan, Manigandan, Khaket, Tejinder Pal, Lee, Hee Gu, Kang, Sun Chul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790463/
https://www.ncbi.nlm.nih.gov/pubmed/29423046
http://dx.doi.org/10.18632/oncotarget.22890
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author Bhardwaj, Monika
Cho, Hee Jun
Paul, Souren
Jakhar, Rekha
Khan, Imran
Lee, Seon-Jin
Kim, Bo-Yeon
Krishnan, Manigandan
Khaket, Tejinder Pal
Lee, Hee Gu
Kang, Sun Chul
author_facet Bhardwaj, Monika
Cho, Hee Jun
Paul, Souren
Jakhar, Rekha
Khan, Imran
Lee, Seon-Jin
Kim, Bo-Yeon
Krishnan, Manigandan
Khaket, Tejinder Pal
Lee, Hee Gu
Kang, Sun Chul
author_sort Bhardwaj, Monika
collection PubMed
description Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitumor effects of vitexin and its underlying mechanisms in a multi-drug resistant human colon cancer cell line (HCT-116(DR)), which exhibits higher levels of multidrug-resistant protein 1 (MDR1) expression as compared with its parental cell line (HCT-116). Here, we observed that vitexin suppressed MDR-1 expression and activity in HCT-116(DR) cells and showed cytotoxic effect in HCT-116(DR) cells by inhibiting autophagy and inducing apoptosis in a concentration-dependent manner. Additionally, vitexin treatment caused cleavage of caspase-9 and caspase-3, and upregulated the expression of the pro-apoptotic proteins, BID and Bax. Moreover, the expression of autophagy-related proteins, such as ATG5, Beclin-1 and LC3-II, was markedly reduced by vitexin treatment. Furthermore, in vivo experiments showed that vitexin induced apoptosis and suppressed tumor growth in HCT-116(DR) xenograft model. These results revealed that vitexin induced apoptosis through suppression of autophagy in vitro and in vivo and provide insight into the therapeutic potential of vitexin for the treatment of chemo-resistant colorectal cancer.
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spelling pubmed-57904632018-02-08 Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells Bhardwaj, Monika Cho, Hee Jun Paul, Souren Jakhar, Rekha Khan, Imran Lee, Seon-Jin Kim, Bo-Yeon Krishnan, Manigandan Khaket, Tejinder Pal Lee, Hee Gu Kang, Sun Chul Oncotarget Research Paper Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitumor effects of vitexin and its underlying mechanisms in a multi-drug resistant human colon cancer cell line (HCT-116(DR)), which exhibits higher levels of multidrug-resistant protein 1 (MDR1) expression as compared with its parental cell line (HCT-116). Here, we observed that vitexin suppressed MDR-1 expression and activity in HCT-116(DR) cells and showed cytotoxic effect in HCT-116(DR) cells by inhibiting autophagy and inducing apoptosis in a concentration-dependent manner. Additionally, vitexin treatment caused cleavage of caspase-9 and caspase-3, and upregulated the expression of the pro-apoptotic proteins, BID and Bax. Moreover, the expression of autophagy-related proteins, such as ATG5, Beclin-1 and LC3-II, was markedly reduced by vitexin treatment. Furthermore, in vivo experiments showed that vitexin induced apoptosis and suppressed tumor growth in HCT-116(DR) xenograft model. These results revealed that vitexin induced apoptosis through suppression of autophagy in vitro and in vivo and provide insight into the therapeutic potential of vitexin for the treatment of chemo-resistant colorectal cancer. Impact Journals LLC 2017-12-04 /pmc/articles/PMC5790463/ /pubmed/29423046 http://dx.doi.org/10.18632/oncotarget.22890 Text en Copyright: © 2018 Bhardwaj et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Bhardwaj, Monika
Cho, Hee Jun
Paul, Souren
Jakhar, Rekha
Khan, Imran
Lee, Seon-Jin
Kim, Bo-Yeon
Krishnan, Manigandan
Khaket, Tejinder Pal
Lee, Hee Gu
Kang, Sun Chul
Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells
title Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells
title_full Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells
title_fullStr Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells
title_full_unstemmed Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells
title_short Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells
title_sort vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790463/
https://www.ncbi.nlm.nih.gov/pubmed/29423046
http://dx.doi.org/10.18632/oncotarget.22890
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