Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells
Glioblastoma multiforme (GBM) is a malignant primary brain tumor. The 5-year relative survival rate of patients with GBM remains <30% on average despite aggressive treatments, and secondary therapy fails in 90% of patients. In chemotherapeutic failure, detoxification proteins are crucial to the a...
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doaj-6317b84dd5a64b249f01d228ff75b4cb2021-07-15T15:38:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-01227080708010.3390/ijms22137080Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme CellsShu-Yu Cheng0Nan-Fu Chen1Zhi-Hong Wen2Zhi-Kang Yao3Kuan-Hao Tsui4Hsiao-Mei Kuo5Wu-Fu Chen6Department of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung City 804, TaiwanDepartment of Surgery, Division of Neurosurgery, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Road, Lingya District, Kaohsiung City 802, TaiwanDepartment of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung City 804, TaiwanDepartment of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung City 804, TaiwanDepartment of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd., Zuoying Dist., Kaohsiung City 813, TaiwanDepartment of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung City 804, TaiwanDepartment of Marine Biotechnology and Resources, National Sun Yat-sen University, No. 70, Lianhai Road, Gushan District, Kaohsiung City 804, TaiwanGlioblastoma multiforme (GBM) is a malignant primary brain tumor. The 5-year relative survival rate of patients with GBM remains <30% on average despite aggressive treatments, and secondary therapy fails in 90% of patients. In chemotherapeutic failure, detoxification proteins are crucial to the activity of chemotherapy drugs. Usually, glutathione S-transferase (GST) superfamily members act as detoxification enzymes by activating xenobiotic metabolites through conjugation with glutathione in healthy cells. However, some overexpressed GSTs not only increase GST activity but also trigger chemotherapy resistance and tumorigenesis-related signaling transductions. Whether GSTM3 is involved in GBM chemoresistance remains unclear. In the current study, we found that T98G, a GBM cell line with pre-existing temozolomide (TMZ) resistance, has high glycolysis and GSTM3 expression. GSTM3 knockdown in T98G decreased glycolysis ability through lactate dehydrogenase A activity reduction. Moreover, it increased TMZ toxicity and decreased invasion ability. Furthermore, we provide next-generation sequencing–based identification of significantly changed messenger RNAs of T98G cells with GSTM3 knockdown for further research. GSTM3 was downregulated in intrinsic TMZ-resistant T98G with a change in the expression levels of some essential glycolysis-related genes. Thus, GSTM3 was associated with glycolysis in chemotherapeutic resistance in T98G cells. Our findings provide new insight into the GSTM3 mechanism in recurring GBM.https://www.mdpi.com/1422-0067/22/13/7080glutathione S-transferase M3glycolysischemotherapeutic resistanceTMZ |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shu-Yu Cheng Nan-Fu Chen Zhi-Hong Wen Zhi-Kang Yao Kuan-Hao Tsui Hsiao-Mei Kuo Wu-Fu Chen |
spellingShingle |
Shu-Yu Cheng Nan-Fu Chen Zhi-Hong Wen Zhi-Kang Yao Kuan-Hao Tsui Hsiao-Mei Kuo Wu-Fu Chen Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells International Journal of Molecular Sciences glutathione S-transferase M3 glycolysis chemotherapeutic resistance TMZ |
author_facet |
Shu-Yu Cheng Nan-Fu Chen Zhi-Hong Wen Zhi-Kang Yao Kuan-Hao Tsui Hsiao-Mei Kuo Wu-Fu Chen |
author_sort |
Shu-Yu Cheng |
title |
Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells |
title_short |
Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells |
title_full |
Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells |
title_fullStr |
Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells |
title_full_unstemmed |
Glutathione S-Transferase M3 Is Associated with Glycolysis in Intrinsic Temozolomide-Resistant Glioblastoma Multiforme Cells |
title_sort |
glutathione s-transferase m3 is associated with glycolysis in intrinsic temozolomide-resistant glioblastoma multiforme cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-06-01 |
description |
Glioblastoma multiforme (GBM) is a malignant primary brain tumor. The 5-year relative survival rate of patients with GBM remains <30% on average despite aggressive treatments, and secondary therapy fails in 90% of patients. In chemotherapeutic failure, detoxification proteins are crucial to the activity of chemotherapy drugs. Usually, glutathione S-transferase (GST) superfamily members act as detoxification enzymes by activating xenobiotic metabolites through conjugation with glutathione in healthy cells. However, some overexpressed GSTs not only increase GST activity but also trigger chemotherapy resistance and tumorigenesis-related signaling transductions. Whether GSTM3 is involved in GBM chemoresistance remains unclear. In the current study, we found that T98G, a GBM cell line with pre-existing temozolomide (TMZ) resistance, has high glycolysis and GSTM3 expression. GSTM3 knockdown in T98G decreased glycolysis ability through lactate dehydrogenase A activity reduction. Moreover, it increased TMZ toxicity and decreased invasion ability. Furthermore, we provide next-generation sequencing–based identification of significantly changed messenger RNAs of T98G cells with GSTM3 knockdown for further research. GSTM3 was downregulated in intrinsic TMZ-resistant T98G with a change in the expression levels of some essential glycolysis-related genes. Thus, GSTM3 was associated with glycolysis in chemotherapeutic resistance in T98G cells. Our findings provide new insight into the GSTM3 mechanism in recurring GBM. |
topic |
glutathione S-transferase M3 glycolysis chemotherapeutic resistance TMZ |
url |
https://www.mdpi.com/1422-0067/22/13/7080 |
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