S-alkylthiolation of O6-methylguanine-DNA-methyltransferase (MGMT) to sensitize cancer cells to anticancer therapy.

Juillerat A; Juillerat-Jeanneret L

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S-alkylthiolation of O6-methylguanine-DNA-methyltransferase (MGMT) to sensitize cancer cells to anticancer therapy.

机译：O6-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）的S-烷硫基化使癌细胞对抗癌治疗敏感。

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O6-methylguanine DNA methyltransferase/O6-alkylguanine DNA alkyltransferase (MGMT/AGT) removes alkyl adducts from the O6-position of guanine in DNA. Expression of MGMT in human cancers has been associated with resistance to therapies using alkylating agents. MGMT promoter methylation regulates its expression and response to alkylating agents. A combination of O6-benzylguanine-based inhibitors of MGMT with alkylating agents improved the efficacy. However, this is associated with enhanced cytotoxicity and the induction of GC to AT transition mutations presumably also in progenitor/stem cells. A few recent studies have described analogs of O6-benzylguanine targeting defined pathways of cancer cells that can be used to improve the selectivity of O6-benzylguanine-based inhibitors for cancer cells. Therefore, MGMT inhibitor targeting represents a reliable strategy for improving cancer therapy with alkylating agents.

机译：O6-甲基鸟嘌呤DNA甲基转移酶/ O6-烷基鸟嘌呤DNA烷基转移酶（MGMT / AGT）从DNA中鸟嘌呤的O6-位置去除烷基加合物。 MGMT在人类癌症中的表达与使用烷基化剂的治疗耐药性有关。 MGMT启动子甲基化调节其表达和对烷基化剂的反应。基于O6-苄基鸟嘌呤的MGMT抑制剂与烷基化剂的组合可提高疗效。但是，这可能与增强的细胞毒性以及祖细胞/干细胞中GC向AT过渡突变的诱导有关。最近的一些研究描述了靶向癌细胞的确定途径的O6-苄基鸟嘌呤类似物，其可用于改善基于O6-苄基鸟嘌呤的抑制剂对癌细胞的选择性。因此，靶向MGMT抑制剂代表了一种使用烷基化剂改善癌症治疗的可靠策略。

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《Expert opinion on therapeutic targets》 |2007年第3期|共13页
作者
Juillerat A; Juillerat-Jeanneret L;
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正文语种 eng
中图分类药学;
关键词
O(6)-Methylguanine-DNA Methyltransferase; Tumor cells; malignant; Alkylating Agents; O(6)-甲基鸟嘌呤DNA甲基转移酶; 烷化剂;

机译：O(6)-Methylguanine-DNA Methyltransferase;Tumor cells;malignant;Alkylating Agents;O(6)-甲基鸟嘌呤DNA甲基转移酶;烷化剂;

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1. S-alkylthiolation of O6-methylguanine-DNA-methyltransferase (MGMT) to sensitize cancer cells to anticancer therapy. [J] . Juillerat A, Juillerat-Jeanneret L Expert opinion on therapeutic targets . 2007,第3期

机译：O6-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）的S-烷硫基化使癌细胞对抗癌治疗敏感。
2. Human adrenomedullin up-regulates interleukin-13 receptor alpha2 chain in prostate cancer in vitro and in vivo: a novel approach to sensitize prostate cancer to anticancer therapy. [J] . Joshi BH, Leland P, Calvo A, Cancer research: The official organ of the American Association for Cancer Research, Inc . 2008,第22期

机译：人肾上腺髓质素在体内和体外上调前列腺癌中的白介素13受体α2链：一种使前列腺癌对抗癌疗法敏感的新方法。
3. Human adrenomedullin up-regulates interleukin-13 receptor alpha2 chain in prostate cancer in vitro and in vivo: a novel approach to sensitize prostate cancer to anticancer therapy. [J] . Joshi BH, Leland P, Calvo A, Cancer research: The official organ of the American Association for Cancer Research, Inc . 2008,第22期

机译：人肾上腺髓质素在体内和体外上调前列腺癌中的白介素13受体α2链：一种使前列腺癌对抗癌疗法敏感的新方法。
4. Synthesis Of 7-Hydroxy-4'-Methoxyflavanone And 7-Hydroxy-4'-Methoxyflavone As A Candidate Anticancer Against Cervical (Hela) Cancer Cell And Colon (Widr) Cancer Cell By In Vitro [C] . Sabirin Matsjeh, Chairil Anwar, Eti Nurwening Solikhah, International Conference on Chemistry, Chemical Process and Engineering . 2017

机译：通过体外合成7-羟基-4'-甲氧化氟酮和7-羟基-4'-甲氧基氟酮和7-羟基-4'-甲氧基硫酮作为颈椎（HELA）癌细胞和结肠（WIDR）癌细胞的候选抗癌
5. The role of NF-kappaB activation in stress-induced resistance of EMT6 cells to anticancer therapy. [D] . Brandes, Lori May. 2002

机译：NF-κB活化在应激诱导的EMT6细胞对抗癌治疗的抗性中的作用。
6. BRD4 Inhibitor AZD5153 Suppresses the Proliferation of Colorectal Cancer Cells and Sensitizes the Anticancer Effect of PARP Inhibitor [O] . Peng Zhang, Ruidong Li, Hua Xiao, 2019

机译：BRD4抑制剂AZD5153抑制大肠癌细胞的增殖并增强PARP抑制剂的抗癌作用
7. Anticancer Activity of Apaziquone in Oral Cancer Cells and Xenograft Model: Implications for Oral Cancer Therapy. [O] . Gunjan Srivastava, Raj Thani Somasundaram, Paul G Walfish, 2015

机译：apaziquone在口腔癌细胞和异种移植模型中的抗癌活性：对口腔癌治疗的启示。
8. Thioredoxin Increases Redox-Cycling of Anticancer Agents Thereby Sensitizes Cancer Cells to Apoptosis. [R] . Dashnamoorthy, R., Das, K. C. 2004

机译：硫氧还蛋白增加抗癌剂的氧化还原循环，从而使癌细胞对细胞凋亡敏感。

S-alkylthiolation of O6-methylguanine-DNA-methyltransferase (MGMT) to sensitize cancer cells to anticancer therapy.

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