Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells

被引：2

作者：

Yang, Zhikuan ^{[1
]}

Wei, Danping ^{[1
]}

Liu, Feifei ^{[1
]}

Liu, Jing ^{[1
]}

Wu, Xiaoming ^{[1
]}

Stevens, Malcolm F. G. ^{[2
]}

Bradshaw, Tracey D. ^{[2
]}

Luo, Ying ^{[1
]}

Zhang, Jihong ^{[1
]}

机构：

[1] Kunming Univ Sci & Technol, Med Sch, Kunming, Yunnan, Peoples R China

[2] Univ Nottingham, Ctr Biomol Sci, Nottingham, England

来源：

JOURNAL OF CELLULAR BIOCHEMISTRY | 2018年 / 119卷 / 07期

基金：

中国国家自然科学基金;

关键词：

colorectal carcinoma; O6-methylguanine-DNA methyltransferase; PMX; 465; p53; Sp1; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE MGMT; SP1 TRANSCRIPTION FACTOR; GLIOBLASTOMA CELLS; GENE-EXPRESSION; GLIOMA-CELLS; REPAIR; TARGET; CANCER; RESISTANCE; PROTEINS;

D O I：

10.1002/jcb.26674

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 tumors. We have found that TMZ analog 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.

引用

页码：5350 / 5358

页数：9

共 22 条

[1] Adenovirus-based strategies overcome temozolomide resistance by silencing the O6-methylguanine-DNA methyltransferase promoter [J].

Alonso, Marta M. ;

Gomez-Manzano, Candelaria ;

Bekele, B. Nebiyou ;

Yung, W. K. Alfred ;

Fueyo, Juan .

CANCER RESEARCH, 2007, 67 (24) :11499-11504

[2]

Bobustuc GC, 2015, PANCREAS, V44, P626, DOI 10.1097/MPA.0000000000000299

[3]

Bocangel D, 2009, ANTICANCER RES, V29, P3741

[4] Regulation of expression of O6-methylguanine-DNA methyltransferase and the treatment of glioblastoma (Review) [J].

Cabrini, Giulio ;

Fabbri, Enrica ;

Lo Nigro, Cristiana ;

Dechecchi, Maria Cristina ;

Gambari, Roberto .

INTERNATIONAL JOURNAL OF ONCOLOGY, 2015, 47 (02) :417-428

[5]

Danam RP, 2005, MOL CANCER THER, V4, P61

[6] O6-methylguanine DNA methyltransferase as a promising target for the treatment of temozolomide-resistant gliomas [J].

Fan, C-H ;

Liu, W-L ;

Cao, H. ;

Wen, C. ;

Chen, L. ;

Jiang, G. .

CELL DEATH & DISEASE, 2013, 4 :e876-e876

[7] Retinoblastoma Binding Protein 4 Modulates Temozolomide Sensitivity in Glioblastoma by Regulating DNA Repair Proteins [J].

Kitange, Gaspar J. ;

Mladek, Ann C. ;

Schroeder, Mark A. ;

Pokorny, Jenny C. ;

Carlson, Brett L. ;

Zhang, Yuji ;

Nair, Asha A. ;

Lee, Jeong-Heon ;

Yan, Huihuang ;

Decker, Paul A. ;

Zhang, Zhiguo ;

Sarkaria, Jann N. .

CELL REPORTS, 2016, 14 (11) :2587-2598

[8] Novel mechanism whereby nuclear factor κB mediates DNA damage repair through regulation of O6-methylguanine-DNA-methyltransferase [J].

Lavon, Iris ;

Fuchs, Dana ;

Zrihan, Daniel ;

Efroni, Gilat ;

Zelikovitch, Bracha ;

Fellig, Yakov ;

Siegalt, Tali .

CANCER RESEARCH, 2007, 67 (18) :8952-8959

[9] Resveratrol enhances the therapeutic effect of temozolomide against malignant glioma in vitro and in vivo by inhibiting autophagy [J].

Lin, Chien-Ju ;

Lee, Chin-Cheng ;

Shih, Yung-Luen ;

Lin, Tsung-Yao ;

Wang, Sheng-Hao ;

Lin, Yuh-Feng ;

Shih, Chwen-Ming .

FREE RADICAL BIOLOGY AND MEDICINE, 2012, 52 (02) :377-391

[10] Significance of Wild-Type p53 Signaling in Suppressing Apoptosis in Response to Chemical Genotoxic Agents: Impact on Chemotherapy Outcome [J].

Mirzayans, Razmik ;

Andrais, Bonnie ;

Kumar, Piyush ;

Murray, David .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2017, 18 (05)

← 1 2 3 →