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

I. Chun Lai, Ping Hsiao Shih, Chih-Jung Yao, Chi-Tai Yeh, Jacqueline Wang-Peng, Tai-Ngar Lui, Suang En Chuang, Tsai Shu Hu, Tung-Yuan Lai, Gi-Ming Lai

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)


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 accompanied with the higher induction of apoptosis, greater down-regulation of Notch3 as well as its downstream Hes1 expressions in SP cells. Our data indicate that Honokiol might have clinical benefits for the GBM patients who are refractory to TMZ treatment.

Original languageEnglish
Article numbere0114830
JournalPLoS ONE
Issue number3
Publication statusPublished - Mar 12 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Elimination of cancer stem-like cells and potentiation of temozolomide sensitivity by honokiol in glioblastoma multiforme cells'. Together they form a unique fingerprint.

Cite this