title: Demethoxycurcumin was superior to temozolomide in the inhibition of the growth of glioblastoma stem cells in vivo.
abstract: Temozolomide (TMZ) is widely used in the treatment of glioblastoma multiforme (GBM) as it can effectively inhibit the growth of GBM for some months; however, this cancer type is still incurable. The existence of glioma stem cells (GSCs) is thought to be responsible for the invariable recurrence of GBM after treatment, but GSCs are insensitive to TMZ. Our recent research showed that demethoxycurcumin (DMC), a component of curcumin, was superior to TMZ in its ability to inhibit proliferation and induce apoptosis of GSCs in vitro. In addition, the combined treatment of TMZ + DMC induced more obvious anti-GSC effects. However, in this study, no obvious synergistic anti-GSC effects of TMZ + DMC were found in vivo, while DMC was still superior to TMZ with respect to growth inhibition of GSCs in vivo. Furthermore, immunohistochemistry for proliferating cell nuclear antigen (PCNA) showed that such inhibitory effects were mainly related to the inhibition of cell proliferation rather than to apoptosis. However, a high concentration of DMC (50 mg/kg) alone or combined with TMZ could also induce approximately 10 % of the cells to undergo apoptosis according to a terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Finally, an investigation of the underlying mechanism revealed that the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) 3 signaling pathway played an important role in the anti-GSC effects. When the JAK inhibitor AG490 was applied, the anti-GSC effects of DMC were enhanced. Taken together, the present work reveals that DMC is superior to TMZ with respect to its anti-GSC effects in vivo, which are mediated through the inhibition of the activation of the JAK/STAT3 pathway; however, DMC demonstrated no synergistic effects with TMZ.
authors.affiliation: Department of Neurosurgery, Liyang People's Hospital Affiliated to Nantong University, Liyang, 213300, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Leng
authors.affiliation: Department of Neurosurgery, Liyang People's Hospital Affiliated to Nantong University, Liyang, 213300, People's Republic of China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Neurosurgery, Fourth Affiliated Yancheng Hospital of Nantong University, Yancheng, 224000, People's Republic of China.
authors.forename: Guan
authors.initials: G
authors.lastname: Sun
authors.affiliation: Department of Immunology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, People's Republic of China. qiuwen@njmu.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Neurosurgery, The First People's Hospital of Kunshan Affiliated with Jiangsu University, Suzhou, 215300, People's Republic of China. sl1012002322@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
keywords: Apoptosis; Demethoxycurcumin; Glioblastoma stem cell; Proliferation; Temozolomide