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Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres

Authors
 Hee Yeon Kim  ;  Byung Il Lee  ;  Ji Hoon Jeon  ;  Dong Keon Kim  ;  Seok-Gu Kang  ;  Jin-Kyoung Shim  ;  Soo Youl Kim  ;  Sang Won Kang  ;  Hyonchol Jang 
Citation
 Biomolecules, Vol.9(10) : 595, 2019 
Journal Title
 Biomolecules 
Issue Date
2019
Keywords
Bcl2 ; dehydrogenase ; glioblastoma ; gossypol ; temozolomide resistance
Abstract
Temozolomide is the current first-line treatment for glioblastoma patients but, because many patients are resistant to it, there is an urgent need to develop antitumor agents to treat temozolomide-resistant glioblastoma. Gossypol, a natural polyphenolic compound, has been studied as a monotherapy or combination therapy for the treatment of glioblastoma. The combination of gossypol and temozolomide has been shown to inhibit glioblastoma, but it is not clear yet whether gossypol alone can suppress temozolomide-resistant glioblastoma. We find that gossypol suppresses the growth of temozolomide-resistant glioblastoma cells in both tumor sphere and adherent culture conditions, with tumor spheres showing the greatest sensitivity. Molecular docking and binding energy calculations show that gossypol has a similar affinity to the Bcl2 (B-cell lymphoma 2) family of proteins and several dehydrogenases. Gossypol reduces mitochondrial membrane potential and cellular ATP levels before cell death, which suggests that gossypol inhibits several dehydrogenases in the cell's metabolic pathway. Treatment with a Bcl2 inhibitor does not fully explain the effect of gossypol on glioblastoma. Overall, this study demonstrates that gossypol can suppress temozolomide-resistant glioblastoma and will be helpful for the refinement of gossypol treatments by elucidating some of the molecular mechanisms of gossypol in glioblastoma.
Files in This Item:
T201904487.pdf Download
DOI
10.3390/biom9100595
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173318
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