A Novel Small-Molecule Inhibitor of SREBP-1 Based on Natural Product Monomers Upregulates the Sensitivity of Lung Squamous Cell Carcinoma Cells to Antitumor Drugs

被引：20

作者：

Ma, De-Bin ^{[1
]}

Liu, Xing-Yu ^{[2
]}

Jia, Hui ^{[3
]}

Zhang, Yingshi ^{[4
]}

Jiang, Qiyu ^{[5
]}

Sun, Huiwei ^{[5
]}

Li, Xiaojuan ^{[5
]}

Sun, Fang ^{[5
]}

Chai, Yantao ^{[6
]}

Feng, Fan ^{[6
]}

Liu, Lei ^{[1
]}

机构：

[1] Gen Hosp Northern Theater Command, Dept Resp & Crit Care Med, Shenyang, Peoples R China

[2] Peoples Liberat Army Gen Hosp, Dept Gen Internal Med, Cent Med Branch, Beijing, Peoples R China

[3] Shenyang Med Coll, Sch Tradit Chinese Med, Shenyang, Peoples R China

[4] Shenyang Pharmaceut Univ, Dept Clin Pharm, Shenyang, Peoples R China

[5] Chinese Peoples Liberat Army Gen Hosp, Inst Infect Dis, Dept Infect Dis, Med Ctr 5, Beijing, Peoples R China

[6] Chinese Peoples Liberat Army Gen Hosp, Dept Clin Lab, Med Ctr 5, Beijing, Peoples R China

来源：

FRONTIERS IN PHARMACOLOGY | 2022年 / 13卷

关键词：

sterol regulatory element binding protein 1; Warburg effect; lung squamous cell carcinoma; antitumor agents; small molecular inhibitor; natural product monomers; TRANSCRIPTION FACTOR ACTIVITY; SORAFENIB-RESISTANCE; KINASE INHIBITOR; CANCER; PROLIFERATION; METABOLISM; ACTIVATION; THERAPIES; INVASION;

D O I：

10.3389/fphar.2022.895744

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The transcription factor, sterol regulatory element binding protein 1 (SREBP-1), plays important roles in modulating the proliferation, metastasis, or resistance to antitumor agents by promoting cellular lipid metabolism and related cellular glucose-uptake/Warburg Effect. However, the underlying mechanism of SREBP-1 regulating the proliferation or drug-resistance in lung squamous cell carcinoma (LUSC) and the therapeutic strategies targeted to SREBP-1 in LUSC remain unclear. In this study, SREBP-1 was highly expressed in LUSC tissues, compared with the paired non-tumor tissues (the para-tumor tissues). A novel small-molecule inhibitor of SREBP-1, MSI-1 (Ma's inhibitor of SREBP-1), based on natural product monomers, was identified by screening the database of natural products. Treatment with MSI-1 suppressed the activation of SREBP-1-related pathways and the Warburg effect of LUSC cells, as indicated by decreased glucose uptake or glycolysis. Moreover, treatment of MSI-1 enhanced the sensitivity of LUSC cells to antitumor agents. The specificity of MSI-1 on SREBP-1 was confirmed by molecular docking and point-mutation of SPEBP-1. Therefore, MSI-1 improved our understanding of SREBP-1 and provided additional options for the treatment of LUSC.

引用

页数：12

共 80 条

[1] KRAS Mutations in Squamous Cell Carcinomas of the Lung [J].

Acker, Fabian ;

Stratmann, Jan ;

Aspacher, Lukas ;

Nguyen, Ngoc Thien Thu ;

Wagner, Sebastian ;

Serve, Hubert ;

Wild, Peter J. ;

Sebastian, Martin .

FRONTIERS IN ONCOLOGY, 2021, 11

[2] Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2 [J].

Cao, Lili ;

Wang, Min ;

Dong, Yujin ;

Xu, Bo ;

Chen, Ju ;

Ding, Yu ;

Qiu, Shusheng ;

Li, Liang ;

Zaharieva, Elena Karamfilova ;

Zhou, Xinwen ;

Xu, Yanbin .

CELL DEATH & DISEASE, 2020, 11 (02)

[3] An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer [J].

Chen, Ming ;

Zhang, Jiangwen ;

Sampieri, Katia ;

Clohessy, John G. ;

Mendez, Lourdes ;

Gonzalez-Billalabeitia, Enrique ;

Liu, Xue-Song ;

Lee, Yu-Ru ;

Fung, Jacqueline ;

Katon, Jesse M. ;

Menon, Archita Venugopal ;

Webster, Kaitlyn A. ;

Ng, Christopher ;

Palumbieri, Maria Dilia ;

Diolombi, Moussa S. ;

Breitkopf, Susanne B. ;

Teruya-Feldstein, Julie ;

Signoretti, Sabina ;

Bronson, Roderick T. ;

Asara, John M. ;

Castillo-Martin, Mireia ;

Cordon-Cardo, Carlos ;

Pandolfi, Pier Paolo .

NATURE GENETICS, 2018, 50 (02) :206-+

[4] Induction of SREBP1 degradation coupled with suppression of SREBP1-mediated lipogenesis impacts the response of EGFR mutant NSCLC cells to osimertinib [J].

Chen, Zhen ;

Yu, Danlei ;

Owonikoko, Taofeek K. ;

Ramalingam, Suresh S. ;

Sun, Shi-Yong .

ONCOGENE, 2021, 40 (49) :6653-6665

[5] FOXO3A-induced LINC00926 suppresses breast tumor growth and metastasis through inhibition of PGK1-mediated Warburg effect [J].

Chu, Zhong ;

Huo, Nan ;

Zhu, Xiang ;

Liu, Hanxiao ;

Cong, Rui ;

Ma, Luyuan ;

Kang, Xiaofeng ;

Xue, Chunyuan ;

Li, Jingtong ;

Li, Qihong ;

You, Hua ;

Zhang, Qingyuan ;

Xu, Xiaojie .

MOLECULAR THERAPY, 2021, 29 (09) :2737-2753

[6] Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline [J].

Daly, Megan E. ;

Ismaila, Nofisat ;

Decker, Roy H. ;

Higgins, Kristin ;

Owen, Dawn ;

Saxena, Ashish ;

Franklin, Gregg E. ;

Donaldson, Dusty ;

Schneider, Bryan J. .

JOURNAL OF CLINICAL ONCOLOGY, 2021, 39 (08) :931-+

[7] The harsh microenvironment in early breast cancer selects for a Warburg phenotype [J].

Damaghi, Mehdi ;

West, Jeffrey ;

Robertson-Tessi, Mark ;

Xu, Liping ;

Ferrall-Fairbanks, Meghan C. ;

Stewart, Paul A. ;

Persi, Erez ;

Fridley, Brooke L. ;

Altrock, Philipp M. ;

Gatenby, Robert A. ;

Sims, Peter A. ;

Anderson, Alexander R. A. ;

Gillies, Robert J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 118 (03)

[8]

De la Cruz PM, 2021, AM J MED SCI, V362, P99, DOI 10.1016/j.amjms.2021.04.003

[9] Metabolic dysregulation and emerging therapeutical targets for hepatocellular carcinoma [J].

Du, Danyu ;

Liu, Chan ;

Qin, Mengyao ;

Zhang, Xiao ;

Xi, Tao ;

Yuan, Shengtao ;

Hao, Haiping ;

Xiong, Jing .

ACTA PHARMACEUTICA SINICA B, 2022, 12 (02) :558-580

[10] Phthalates promote the invasion of hepatocellular carcinoma cells by enhancing the interaction between Pregnane X receptor and E26 transformation specific sequence 1 [J].

Du, Yabing ;

Shi, Xiaoyi ;

Ma, Wang ;

Wen, Peihao ;

Yu, Pu ;

Wang, Xin ;

Fang, Pengli ;

Chen, Aixia ;

Gao, Zhiqiang ;

Cui, Kang .

PHARMACOLOGICAL RESEARCH, 2021, 169

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