Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783296448349077504 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5790463 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT bhardwajmonika vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT choheejun vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT paulsouren vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT jakharrekha vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT khanimran vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT leeseonjin vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT kimboyeon vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT krishnanmanigandan vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT khakettejinderpal vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT leeheegu vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells AT kangsunchul vitexininducesapoptosisbysuppressingautophagyinmultidrugresistantcolorectalcancercells |