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Combined treatment with 2′-hydroxycinnamaldehyde and temozolomide suppresses glioblastoma tumorspheres by decreasing stemness and invasiveness

Authors
 Hyewon Jeong  ;  Junseong Park  ;  Jin-Kyoung Shim  ;  Jae Eun Lee  ;  Nam Hee Kim  ;  Hyun Sil Kim  ;  Jong Hee Chang  ;  Jong In Yook  ;  Seok-Gu Kang 
Citation
 JOURNAL OF NEURO-ONCOLOGY, Vol.143(1) : 69-77, 2019 
Journal Title
 JOURNAL OF NEURO-ONCOLOGY 
ISSN
 0167-594X 
Issue Date
2019
Keywords
2′-Benzoyloxycinnamaldehyde ; 2′-Hydroxycinnamaldehyde ; Glioblastoma tumorsphere ; Invasiveness ; Mesenchymal transition ; Temozolomide
Abstract
INTRODUCTION: Glioblastoma (GBM) is the most common and aggressive human primary brain malignancy. The key properties of GBM, stemness and invasiveness, are known to be associated with a highly unfavorable prognosis. Notably, the process of epithelial-mesenchymal transition (EMT) is closely related to the progression of GBM. On the basis of reports that 2'-hydroxycinnamaldehyde (HCA) and its derivative, 2'-benzoyloxycinnamaldehyde (BCA), suppresses EMT in several human cancer cells, we sought to evaluate the therapeutic efficacy of HCA and BCA, alone and in combination with temozolomide (TMZ), on GBM tumorspheres (TSs). METHODS: Two human GBM TSs were treated with HCA, BCA, or TMZ. Therapeutic effects were evaluated by measuring ATP levels, neurosphere formation, 3D-invasion in collagen matrix, and viability. Protein expression profiles after drug treatment were evaluated by western blotting. In vivo anticancer efficacy of drugs was examined in a mouse orthotopic xenograft model. RESULTS: Combined treatment of GBM TSs with HCA or BCA and TMZ significantly reduced cell viability, stemness, and invasiveness. Expression levels of stemness-, invasiveness-, and mesenchymal transition-associated markers, Zeb1, N-cadherin, and β-catenin, were also substantially decreased by the combined treatment. The combined treatment also reduced tumor growth in a mouse orthotopic xenograft model. CONCLUSION: Our findings suggest that HCA and BCA, combined with TMZ, are potential therapeutic agents in the treatment of GBM.
Full Text
https://link.springer.com/article/10.1007%2Fs11060-019-03151-w
DOI
10.1007/s11060-019-03151-w
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Chang, Jong Hee(장종희)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/170310
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