Cargando…
Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo
Arsenic trioxide (ATO) is clinically used to treat acute promyelocytic leukemia (APL); however, the therapeutic dose of ATO may prompt critical cardiac side effects. Combination therapy may be used to improve the therapeutic efficiency. To evaluate this possibility, the present study determined the...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450767/ https://www.ncbi.nlm.nih.gov/pubmed/28587418 http://dx.doi.org/10.3892/etm.2017.4392 |
_version_ | 1783240053856665600 |
---|---|
author | Kuo, Yu-Jui Liu, Yan-Jin Way, Tzong-Der Chiang, Su-Yin Lin, Jaung-Geng Chung, Jing-Gung |
author_facet | Kuo, Yu-Jui Liu, Yan-Jin Way, Tzong-Der Chiang, Su-Yin Lin, Jaung-Geng Chung, Jing-Gung |
author_sort | Kuo, Yu-Jui |
collection | PubMed |
description | Arsenic trioxide (ATO) is clinically used to treat acute promyelocytic leukemia (APL); however, the therapeutic dose of ATO may prompt critical cardiac side effects. Combination therapy may be used to improve the therapeutic efficiency. To evaluate this possibility, the present study determined the combined effects of Hedyotis diffusa Willd (HDW) extract and ATO in leukemic WEHI-3 cells. The results demonstrated that co-treatment of HDW with ATO resulted in a synergistic augmentation of cytotoxicity in cells at the concentration tested. In order to investigate the potential therapeutic application for leukemia, the combined effects of HDW and ATO were analyzed on the WEHI-3 cell-induced orthotopic leukemia animal model in vivo. The WEHI-3 cells in mice with leukemia were established by injecting murine WEHI-3 cells into BALB/c mice, and treating them with HDW and/or combined with ATO. The results indicated that HDW alone or HDW combined with ATO promoted the total survival rate of mice with leukemia, and these effects are dose-dependent. HDW alone or HDW combined with ATO did not affect the body weight, decreased the spleen weight and did not affect the liver weight. Furthermore, the results demonstrated that HDW alone or HDW combined with ATO resulted in a synergistic augmentation of apoptosis in WEHI-3 cells at the concentration tested. In order to further reveal the detailed mechanism of this synergistic effect on apoptosis, apoptosis-related proteins were also evaluated. The data revealed that HDW alone or HDW combined with ATO induced the expression of death receptor 4 (DR4) and DR5 and the activation of poly adenosine diphosphate ribose polymerase, caspase-3, −8 and −9. Furthermore, HDW alone or HDW combined with ATO decreased the expression levels of B-cell lymphoma 2, B-cell lymphoma-extra large and survivin, and increased the expression levels of Bak and t-Bid. Altogether, the results indicate that the combination of HDW with ATO may be a promising strategy used to increase the clinical efficacy of ATO in the treatment of APL. |
format | Online Article Text |
id | pubmed-5450767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-54507672017-06-05 Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo Kuo, Yu-Jui Liu, Yan-Jin Way, Tzong-Der Chiang, Su-Yin Lin, Jaung-Geng Chung, Jing-Gung Exp Ther Med Articles Arsenic trioxide (ATO) is clinically used to treat acute promyelocytic leukemia (APL); however, the therapeutic dose of ATO may prompt critical cardiac side effects. Combination therapy may be used to improve the therapeutic efficiency. To evaluate this possibility, the present study determined the combined effects of Hedyotis diffusa Willd (HDW) extract and ATO in leukemic WEHI-3 cells. The results demonstrated that co-treatment of HDW with ATO resulted in a synergistic augmentation of cytotoxicity in cells at the concentration tested. In order to investigate the potential therapeutic application for leukemia, the combined effects of HDW and ATO were analyzed on the WEHI-3 cell-induced orthotopic leukemia animal model in vivo. The WEHI-3 cells in mice with leukemia were established by injecting murine WEHI-3 cells into BALB/c mice, and treating them with HDW and/or combined with ATO. The results indicated that HDW alone or HDW combined with ATO promoted the total survival rate of mice with leukemia, and these effects are dose-dependent. HDW alone or HDW combined with ATO did not affect the body weight, decreased the spleen weight and did not affect the liver weight. Furthermore, the results demonstrated that HDW alone or HDW combined with ATO resulted in a synergistic augmentation of apoptosis in WEHI-3 cells at the concentration tested. In order to further reveal the detailed mechanism of this synergistic effect on apoptosis, apoptosis-related proteins were also evaluated. The data revealed that HDW alone or HDW combined with ATO induced the expression of death receptor 4 (DR4) and DR5 and the activation of poly adenosine diphosphate ribose polymerase, caspase-3, −8 and −9. Furthermore, HDW alone or HDW combined with ATO decreased the expression levels of B-cell lymphoma 2, B-cell lymphoma-extra large and survivin, and increased the expression levels of Bak and t-Bid. Altogether, the results indicate that the combination of HDW with ATO may be a promising strategy used to increase the clinical efficacy of ATO in the treatment of APL. D.A. Spandidos 2017-06 2017-04-27 /pmc/articles/PMC5450767/ /pubmed/28587418 http://dx.doi.org/10.3892/etm.2017.4392 Text en Copyright: © Kuo et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Kuo, Yu-Jui Liu, Yan-Jin Way, Tzong-Der Chiang, Su-Yin Lin, Jaung-Geng Chung, Jing-Gung Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo |
title | Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo |
title_full | Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo |
title_fullStr | Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo |
title_full_unstemmed | Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo |
title_short | Synergistic inhibition of leukemia WEHI-3 cell growth by arsenic trioxide and Hedyotis diffusa Willd extract in vitro and in vivo |
title_sort | synergistic inhibition of leukemia wehi-3 cell growth by arsenic trioxide and hedyotis diffusa willd extract in vitro and in vivo |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450767/ https://www.ncbi.nlm.nih.gov/pubmed/28587418 http://dx.doi.org/10.3892/etm.2017.4392 |
work_keys_str_mv | AT kuoyujui synergisticinhibitionofleukemiawehi3cellgrowthbyarsenictrioxideandhedyotisdiffusawilldextractinvitroandinvivo AT liuyanjin synergisticinhibitionofleukemiawehi3cellgrowthbyarsenictrioxideandhedyotisdiffusawilldextractinvitroandinvivo AT waytzongder synergisticinhibitionofleukemiawehi3cellgrowthbyarsenictrioxideandhedyotisdiffusawilldextractinvitroandinvivo AT chiangsuyin synergisticinhibitionofleukemiawehi3cellgrowthbyarsenictrioxideandhedyotisdiffusawilldextractinvitroandinvivo AT linjaunggeng synergisticinhibitionofleukemiawehi3cellgrowthbyarsenictrioxideandhedyotisdiffusawilldextractinvitroandinvivo AT chungjinggung synergisticinhibitionofleukemiawehi3cellgrowthbyarsenictrioxideandhedyotisdiffusawilldextractinvitroandinvivo |