國家衛生研究院 NHRI:Item 3990099045/9905

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Title:	Induction of autophagy and elimination of cancer stem-like cell in glioblastoma multiforme cells by a Magnolia officinalis active component honokiol
Authors:	Yao, CJ;Hong, CY;Shih, PH;Yeh, CT;Chen, RM;Chuang, SE;Lin, PC;Yi, TY;Lai, GM
Contributors:	National Institute of Cancer Research
Abstract:	The anticancer effects of honokiol, an active component isolated from Chinese traditional herb Magnolia officinalis, had been noticed in recent decade. It had been reported to induce apoptosis, anti-agiogenesis and chemo/radio-sensitization on cancer cells. However, its effects on autophagy induction and cancer stem cell elimination have not yet been investigated. To more evaluate the potential of honokiol in cancer therapy, we explored its effects on these two critical events in glioblastoma multiforme (GBM) DBTRG-05MG cells. The honokiol-induced autophagy was evidenced by the time and dose-dependent increase of LC3-II in treated cells. During this autophagy induction, the phosphorylated AMP-dependent kinase alpha was dose-dependently increased in accompany with the decrease of phosphorylated mTOR protein level. In addition, the phosphorylated p38 was also markedly increased parallel with the elevation of LC3-II. Further investigation on the role of this MAPK p38 pathway in honokiol-induced autophagy is ongoing. In accordance with the growth inhibition and massive cell death induced by high dose of honokiol (50 μM), the phsphorylated Akt and Rb were dramatically suppressed in treated cells. As it is suggested that autophagy is a protective response of cancer cell to environmental stress, an autophagy inhibitor hydroxychloroquine was therefore co-administrated to enhance the effects of honokiol against GBM cells. Significantly, hydroxychloroquine augmented the honokiol-induced cell death, indicating the crucial role of autophagy in honokiol-induced anticancer effects. Moreover, honokiol appeared to have effects on the elimination of cancer stem-like cells. By UV laser-equipped flow cytometer, a small percentage of cancer stem-like side population (SP) cells was detected and sorted from another GBM cell line (GBM 8401). The expressions of stemness genes such as CD133, nestin, Oct4, NOTCH3, IHH and SMO in SP cells were much higher than those in non-SP cells. Treatment with honokiol (5 μM) for 48h decreased the percentage of GBM 8401 SP cells from 1.5% down to 0.2%. These results suggested the potential role of honokiol in GBM treatment.
Date:	2011-04
Relation:	Cancer Research. 2011 Apr;71(Suppl. 8):Meeting Abstract 3778.
Link to:	http://dx.doi.org/10.1158/1538-7445.AM2011-3778
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000209701400104
Appears in Collections:	[Shuang-En Chuang] Conference Papers/Meeting Abstract

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