Honokiol Enhances Paclitaxel Efficacy in Multi-Drug Resistant Human Cancer Model through the Induction of Apoptosis

Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human M...

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Autores principales: Wang, Xu, Beitler, Jonathan J., Wang, Hong, Lee, Michael J., Huang, Wen, Koenig, Lydia, Nannapaneni, Sreenivas, Amin, A. R. M. Ruhul, Bonner, Michael, Shin, Hyung Ju C., Chen, Zhuo Georgia, Arbiser, Jack L., Shin, Dong M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934844/
https://www.ncbi.nlm.nih.gov/pubmed/24586249
http://dx.doi.org/10.1371/journal.pone.0086369
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author Wang, Xu
Beitler, Jonathan J.
Wang, Hong
Lee, Michael J.
Huang, Wen
Koenig, Lydia
Nannapaneni, Sreenivas
Amin, A. R. M. Ruhul
Bonner, Michael
Shin, Hyung Ju C.
Chen, Zhuo Georgia
Arbiser, Jack L.
Shin, Dong M.
author_facet Wang, Xu
Beitler, Jonathan J.
Wang, Hong
Lee, Michael J.
Huang, Wen
Koenig, Lydia
Nannapaneni, Sreenivas
Amin, A. R. M. Ruhul
Bonner, Michael
Shin, Hyung Ju C.
Chen, Zhuo Georgia
Arbiser, Jack L.
Shin, Dong M.
author_sort Wang, Xu
collection PubMed
description Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC(50) ranging 3.35±0.13 µg/ml to 2.77±0.22 µg/ml), despite their significant differences in response to paclitaxel (IC(50) ranging 1.66±0.09 ng/ml to 6560.9±439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in MDR KB cells, which was associated with inhibition of EGFR-STAT3 signaling and downregulation of STAT3 target genes. Combined treatment with honokiol and paclitaxel synergistically augmented cytotoxicity in MDR KB cells, compared with treatment with either agent alone in vitro. Importantly, the combined treatment significantly inhibited in vivo growth of KB-8-5 tumors in a subcutaneous model. Tumor tissues from the combination group displayed a significant inhibition of Ki-67 expression and an increase in TUNEL-positive cells compared with the control group. These results suggest that targeting multidrug resistance using honokiol in combination with chemotherapy drugs may provide novel therapeutic opportunities.
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spelling pubmed-39348442014-03-04 Honokiol Enhances Paclitaxel Efficacy in Multi-Drug Resistant Human Cancer Model through the Induction of Apoptosis Wang, Xu Beitler, Jonathan J. Wang, Hong Lee, Michael J. Huang, Wen Koenig, Lydia Nannapaneni, Sreenivas Amin, A. R. M. Ruhul Bonner, Michael Shin, Hyung Ju C. Chen, Zhuo Georgia Arbiser, Jack L. Shin, Dong M. PLoS One Research Article Resistance to chemotherapy remains a major obstacle in cancer therapy. This study aimed to evaluate the molecular mechanism and efficacy of honokiol in inducing apoptosis and enhancing paclitaxel chemotherapy in pre-clinical multi-drug resistant (MDR) cancer models, including lineage-derived human MDR (KB-8-5, KB-C1, KB-V1) and their parental drug sensitive KB-3-1 cancer cell lines. In vitro analyses demonstrated that honokiol effectively inhibited proliferation in KB-3-1 cells and the MDR derivatives (IC(50) ranging 3.35±0.13 µg/ml to 2.77±0.22 µg/ml), despite their significant differences in response to paclitaxel (IC(50) ranging 1.66±0.09 ng/ml to 6560.9±439.52 ng/ml). Honokiol induced mitochondria-dependent and death receptor-mediated apoptosis in MDR KB cells, which was associated with inhibition of EGFR-STAT3 signaling and downregulation of STAT3 target genes. Combined treatment with honokiol and paclitaxel synergistically augmented cytotoxicity in MDR KB cells, compared with treatment with either agent alone in vitro. Importantly, the combined treatment significantly inhibited in vivo growth of KB-8-5 tumors in a subcutaneous model. Tumor tissues from the combination group displayed a significant inhibition of Ki-67 expression and an increase in TUNEL-positive cells compared with the control group. These results suggest that targeting multidrug resistance using honokiol in combination with chemotherapy drugs may provide novel therapeutic opportunities. Public Library of Science 2014-02-25 /pmc/articles/PMC3934844/ /pubmed/24586249 http://dx.doi.org/10.1371/journal.pone.0086369 Text en © 2014 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wang, Xu
Beitler, Jonathan J.
Wang, Hong
Lee, Michael J.
Huang, Wen
Koenig, Lydia
Nannapaneni, Sreenivas
Amin, A. R. M. Ruhul
Bonner, Michael
Shin, Hyung Ju C.
Chen, Zhuo Georgia
Arbiser, Jack L.
Shin, Dong M.
Honokiol Enhances Paclitaxel Efficacy in Multi-Drug Resistant Human Cancer Model through the Induction of Apoptosis
title Honokiol Enhances Paclitaxel Efficacy in Multi-Drug Resistant Human Cancer Model through the Induction of Apoptosis
title_full Honokiol Enhances Paclitaxel Efficacy in Multi-Drug Resistant Human Cancer Model through the Induction of Apoptosis
title_fullStr Honokiol Enhances Paclitaxel Efficacy in Multi-Drug Resistant Human Cancer Model through the Induction of Apoptosis
title_full_unstemmed Honokiol Enhances Paclitaxel Efficacy in Multi-Drug Resistant Human Cancer Model through the Induction of Apoptosis
title_short Honokiol Enhances Paclitaxel Efficacy in Multi-Drug Resistant Human Cancer Model through the Induction of Apoptosis
title_sort honokiol enhances paclitaxel efficacy in multi-drug resistant human cancer model through the induction of apoptosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934844/
https://www.ncbi.nlm.nih.gov/pubmed/24586249
http://dx.doi.org/10.1371/journal.pone.0086369
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