Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres
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...
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doaj-4225a5f49be94ba184aca17df20379582020-11-25T02:13:00ZengMDPI AGBiomolecules2218-273X2019-10-0191059510.3390/biom9100595biom9100595Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor SpheresHee Yeon Kim0Byung Il Lee1Ji Hoon Jeon2Dong Keon Kim3Seok-Gu Kang4Jin-Kyoung Shim5Soo Youl Kim6Sang Won Kang7Hyonchol Jang8Division of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, KoreaDivision of Precision Medicine, Research Institute, National Cancer Center, Goyang 10408, KoreaDivision of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, KoreaDivision of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, KoreaDepartment of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDivision of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, KoreaDepartment of Life Science, Ewha Womans University, Seoul 03760, KoreaDivision of Cancer Biology, Research Institute, National Cancer Center, Goyang 10408, KoreaTemozolomide 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.https://www.mdpi.com/2218-273X/9/10/595bcl2dehydrogenaseglioblastomagossypoltemozolomide resistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres Biomolecules bcl2 dehydrogenase glioblastoma gossypol temozolomide resistance |
author_facet |
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 |
author_sort |
Hee Yeon Kim |
title |
Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres |
title_short |
Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres |
title_full |
Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres |
title_fullStr |
Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres |
title_full_unstemmed |
Gossypol Suppresses Growth of Temozolomide-Resistant Glioblastoma Tumor Spheres |
title_sort |
gossypol suppresses growth of temozolomide-resistant glioblastoma tumor spheres |
publisher |
MDPI AG |
series |
Biomolecules |
issn |
2218-273X |
publishDate |
2019-10-01 |
description |
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. |
topic |
bcl2 dehydrogenase glioblastoma gossypol temozolomide resistance |
url |
https://www.mdpi.com/2218-273X/9/10/595 |
work_keys_str_mv |
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