Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells
The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in a significant proportion of tumours. We have...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
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Wiley
2018
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| Online Access: | https://eprints.nottingham.ac.uk/49220/ |
| _version_ | 1848797948479012864 |
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| author | Yang, Zhikuan Wei, Danping Liu, Feifei Liu, Jing Wu, Xiaoming Stevens, Malcolm F. G. Bradshaw, Tracey D. Luo, Ying Zhang, Jihong |
| author_facet | Yang, Zhikuan Wei, Danping Liu, Feifei Liu, Jing Wu, Xiaoming Stevens, Malcolm F. G. Bradshaw, Tracey D. Luo, Ying Zhang, Jihong |
| author_sort | Yang, Zhikuan |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in a significant proportion of tumours. We have found that TMZ analogue C8-methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against the colorectal carcinoma HCT116 cells which are MGMT-overexpressing and mismatch repair (MMR)-deficient. In this study, we found that PMX 465 could downregulate the expression of MGMT in HCT116 cells at the protein and mRNA levels. We found that PMX 465 could reduce MGMT expression by increasing the binding of wild-type p53 to the MGMT promoter and reducing the binding of Sp1 to the MGMT promoter. |
| first_indexed | 2025-11-14T20:11:59Z |
| format | Article |
| id | nottingham-49220 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:11:59Z |
| publishDate | 2018 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-492202020-05-04T19:26:35Z https://eprints.nottingham.ac.uk/49220/ Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells Yang, Zhikuan Wei, Danping Liu, Feifei Liu, Jing Wu, Xiaoming Stevens, Malcolm F. G. Bradshaw, Tracey D. Luo, Ying Zhang, Jihong The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in a significant proportion of tumours. We have found that TMZ analogue C8-methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against the colorectal carcinoma HCT116 cells which are MGMT-overexpressing and mismatch repair (MMR)-deficient. In this study, we found that PMX 465 could downregulate the expression of MGMT in HCT116 cells at the protein and mRNA levels. We found that PMX 465 could reduce MGMT expression by increasing the binding of wild-type p53 to the MGMT promoter and reducing the binding of Sp1 to the MGMT promoter. Wiley 2018-01-13 Article PeerReviewed Yang, Zhikuan, Wei, Danping, Liu, Feifei, Liu, Jing, Wu, Xiaoming, Stevens, Malcolm F. G., Bradshaw, Tracey D., Luo, Ying and Zhang, Jihong (2018) Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells. Journal of Cellular Biochemistry . ISSN 0730-2312 PMX 465 ; O6-methylguanine-DNA methyltransferase ; p53 ; Sp1 ; Colorectal carcinoma http://onlinelibrary.wiley.com/doi/10.1002/jcb.26674/pdf doi:10.1002/jcb.26674 doi:10.1002/jcb.26674 |
| spellingShingle | PMX 465 ; O6-methylguanine-DNA methyltransferase ; p53 ; Sp1 ; Colorectal carcinoma Yang, Zhikuan Wei, Danping Liu, Feifei Liu, Jing Wu, Xiaoming Stevens, Malcolm F. G. Bradshaw, Tracey D. Luo, Ying Zhang, Jihong Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells |
| title | Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells |
| title_full | Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells |
| title_fullStr | Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells |
| title_full_unstemmed | Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells |
| title_short | Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells |
| title_sort | temozolomide analog pmx 465 downregulates mgmt expression in hct116 colorectal carcinoma cells |
| topic | PMX 465 ; O6-methylguanine-DNA methyltransferase ; p53 ; Sp1 ; Colorectal carcinoma |
| url | https://eprints.nottingham.ac.uk/49220/ https://eprints.nottingham.ac.uk/49220/ https://eprints.nottingham.ac.uk/49220/ |