title: β-Elemene Selectively Inhibits the Proliferation of Glioma Stem-Like Cells Through the Downregulation of Notch1.
abstract: Glioma is the most frequent primary central nervous system tumor. Although the current first-line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β-Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem-like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects. The molecular mechanisms were also investigated. We also optimized the delivery methods of bELE. We found that bELE selectively inhibits the proliferation and sphere formation of GSLCs, other than parental glioma cells, and TMZ exerts its effects on parental cells instead of GSLCs. The in vivo data confirmed that the combination of bELE and TMZ worked better in the xenografts of GSLCs, mimicking the situation of tumorigenesis of human cancer. Notch1 was downregulated with bELE treatment. Our data also demonstrated that the continuous administration of bELE produces an ideal effect to control tumor progression. Our findings have demonstrated, for the first time, that bELE could compensate for TMZ to kill both GSLCs and nonstem-like cancer cells, probably improving the prognosis of glioma patients tremendously. Notch1 might be a downstream target of bELE. Therefore, our data shed light on improving the outcomes of glioma patients by combining bELE and TMZ. Stem Cells Translational Medicine 2017;6:830-839.
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Department of Neurosurgery, Nongken Central Hospital of Guangdong, Zhanjiang, Guangdong, People's Republic of China.
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Feng
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Department of Neurosurgery, Huizhou First People's Hospital, Huizhou, Guangdong, People's Republic of China.
authors.forename: Hao-Ran
authors.initials: HR
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Mei
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yi-Ying
authors.initials: YY
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Fu-Rong
authors.initials: FR
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.|Department of Pharmacology, School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Sai
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Nongken Central Hospital of Guangdong, Zhanjiang, Guangdong, People's Republic of China.
authors.forename: Zong-Ping
authors.initials: ZP
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery/Neuro-Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, People's Republic of China.
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Chen
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D004357:Drug Synergism; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008297:Male; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051881:Receptor, Notch1 / Q000378:metabolism*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000077204:Temozolomide / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D051881:Receptor, Notch1; D012717:Sesquiterpenes; C445979:beta-elemene; D000077204:Temozolomide
keywords: Glioma stem-like cell; Proliferation; Temozolomide; β-Elemene