Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas

Glioblastoma (GBM) is a malignant brain tumor associated with a high mortality rate. The aim of this study is to investigate the synergistic effects of honokiol (Hono) and magnolol (Mag), extracted from Magnolia officinalis, on cytotoxicity and inhibition of human GBM tumor progression in cellular a...

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Main Authors:	Cheng, Yu-Chen, Hueng, Dueng-Yuan, Huang, Hua-Yin, Chen, Jang-Yi, Chen, Ying
Format:	Online
Language:	English
Published:	Impact Journals LLC 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045382/

id	pubmed-5045382
recordtype	oai_dc
spelling	pubmed-50453822016-10-13 Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas Cheng, Yu-Chen Hueng, Dueng-Yuan Huang, Hua-Yin Chen, Jang-Yi Chen, Ying Research Paper Glioblastoma (GBM) is a malignant brain tumor associated with a high mortality rate. The aim of this study is to investigate the synergistic effects of honokiol (Hono) and magnolol (Mag), extracted from Magnolia officinalis, on cytotoxicity and inhibition of human GBM tumor progression in cellular and animal models. In comparison with Hono or Mag alone, co-treatment with Hono and Mag (Hono-Mag) decreased cyclin A, D1 and cyclin-dependent kinase 2, 4, 6 significantly, leading to cell cycle arrest in U87MG and LN229 human glioma cells. In addition, phosphorylated phosphoinositide 3-kinase (p-PI3K), p-Akt, and Ki67 were decreased after Hono-Mag treatment, showing proliferation inhibition. Hono-Mag treatment also reduced p-p38 and p-JNK but elevated p-ERK expression. Besides, Hono-Mag treatment induced autophagy and intrinsic and extrinsic apoptosis. Both ERK and autophagy inhibitors enhanced Hono-Mag-induced apoptosis in LN229 cells, indicating a rescuer role of ERK. In human GBM orthotopic xenograft model, the Hono-Mag treatment inhibited the tumor progression and induced apoptosis more efficiently than Temozolomide, Hono, or Mag group. In conclusion, the Hono-Mag exerts a synergistic anti-tumor effect by inhibiting cell proliferation and inducing autophagy and apoptosis in human GBM cells. The Hono-Mag may be applied as an adjuvant therapy to improve the therapeutic efficacy of GBM treatment. Impact Journals LLC 2016-04-11 /pmc/articles/PMC5045382/ /pubmed/27074557 http://dx.doi.org/10.18632/oncotarget.8674 Text en Copyright: © 2016 Cheng et al. http://creativecommons.org/licenses/by/2.5/ 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 credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Cheng, Yu-Chen Hueng, Dueng-Yuan Huang, Hua-Yin Chen, Jang-Yi Chen, Ying
spellingShingle	Cheng, Yu-Chen Hueng, Dueng-Yuan Huang, Hua-Yin Chen, Jang-Yi Chen, Ying Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas
author_facet	Cheng, Yu-Chen Hueng, Dueng-Yuan Huang, Hua-Yin Chen, Jang-Yi Chen, Ying
author_sort	Cheng, Yu-Chen
title	Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas
title_short	Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas
title_full	Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas
title_fullStr	Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas
title_full_unstemmed	Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas
title_sort	magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas
description	Glioblastoma (GBM) is a malignant brain tumor associated with a high mortality rate. The aim of this study is to investigate the synergistic effects of honokiol (Hono) and magnolol (Mag), extracted from Magnolia officinalis, on cytotoxicity and inhibition of human GBM tumor progression in cellular and animal models. In comparison with Hono or Mag alone, co-treatment with Hono and Mag (Hono-Mag) decreased cyclin A, D1 and cyclin-dependent kinase 2, 4, 6 significantly, leading to cell cycle arrest in U87MG and LN229 human glioma cells. In addition, phosphorylated phosphoinositide 3-kinase (p-PI3K), p-Akt, and Ki67 were decreased after Hono-Mag treatment, showing proliferation inhibition. Hono-Mag treatment also reduced p-p38 and p-JNK but elevated p-ERK expression. Besides, Hono-Mag treatment induced autophagy and intrinsic and extrinsic apoptosis. Both ERK and autophagy inhibitors enhanced Hono-Mag-induced apoptosis in LN229 cells, indicating a rescuer role of ERK. In human GBM orthotopic xenograft model, the Hono-Mag treatment inhibited the tumor progression and induced apoptosis more efficiently than Temozolomide, Hono, or Mag group. In conclusion, the Hono-Mag exerts a synergistic anti-tumor effect by inhibiting cell proliferation and inducing autophagy and apoptosis in human GBM cells. The Hono-Mag may be applied as an adjuvant therapy to improve the therapeutic efficacy of GBM treatment.
publisher	Impact Journals LLC
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045382/
_version_	1613668665213845504

Magnolol and honokiol exert a synergistic anti-tumor effect through autophagy and apoptosis in human glioblastomas

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