Elimination of cancer stem-like cells and potentiation of temozolomide sensitivity by Honokiol in glioblastoma multiforme cells

PloS One
I-Chun LaiGi-Ming Lai

Abstract

Glioblastoma multiforme (GBM) is the most common adult malignant glioma with poor prognosis due to the resistance to radiotherapy and chemotherapy, which might be critically involved in the repopulation of cancer stem cells (CSCs) after treatment. We had investigated the characteristics of cancer stem-like side population (SP) cells sorted from GBM cells, and studied the effect of Honokiol targeting on CSCs. GBM8401 SP cells possessed the stem cell markers, such as nestin, CD133 and Oct4, and the expressions of self-renewal related stemness genes, such as SMO, Notch3 and IHH (Indian Hedgehog). Honokiol inhibited the proliferation of both GBM8401 parental cells and SP cells in a dose-dependent manner, the IC50 were 5.3±0.72 and 11±1.1 μM, respectively. The proportions of SP in GBM8401 cells were diminished by Honokiol from 1.5±0.22% down to 0.3±0.02% and 0.2±0.01% at doses of 2.5 μM and 5 μM, respectively. The SP cells appeared to have higher expression of O6-methylguanine-DNA methyltransferase (MGMT) and be more resistant to Temozolomide (TMZ). The resistance to TMZ could be only slightly reversed by MGMT inhibitor O6-benzylguanine (O6-BG), but markedly further enhanced by Honokiol addition. Such significant enhancement was acc...Continue Reading

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Citations

Apr 20, 2016·Experimental Cell Research·Jun-Hai TangSheng-Qing Lv
Dec 28, 2019·Cancers·Chon Phin OngWei Hsum Yap
Apr 17, 2019·Experimental and Therapeutic Medicine·Chi-Hao HsiaoPing-Hsiao Shih
Jun 9, 2016·Molecular Nutrition & Food Research·Jing PanMing You
Mar 6, 2019·Cancers·Riccardo Bazzoni, Angela Bentivegna
Apr 16, 2020·Frontiers in Pharmacology·Andrea J Yool, Sunita Ramesh

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Methods Mentioned

BETA
flow cytometry
PCR

Software Mentioned

DIVA
CXP

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