Autophagy Modulators in Cancer Therapy

被引:52
作者
Buzun, Kamila [1 ]
Gornowicz, Agnieszka [1 ]
Lesyk, Roman [2 ]
Bielawski, Krzysztof [3 ]
Bielawska, Anna [1 ]
机构
[1] Med Univ Bialystok, Fac Pharm, Dept Biotechnol, PL-15089 Bialystok, Poland
[2] Univ Informat Technol & Management Rzeszow, Dept Publ Hlth Dietet & Lifestyle Disorders, Fac Med, PL-35225 Rzeszow, Poland
[3] Med Univ Bialystok, Fac Pharm, Dept Synth & Technol Drugs, PL-15089 Bialystok, Poland
关键词
autophagy; autophagy inhibitors; autophagy activators; cancer; cancer therapy; CHAPERONE-MEDIATED AUTOPHAGY; CELL-CYCLE ARREST; SELECTIVE AUTOPHAGY; ANTITUMOR-ACTIVITY; INDUCED APOPTOSIS; JNK1-MEDIATED PHOSPHORYLATION; MOLECULAR-MECHANISMS; REGULATES AUTOPHAGY; SIGNALING PATHWAYS; CYTOSOLIC PROTEINS;
D O I
10.3390/ijms22115804
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
Autophagy is a process of self-degradation that plays an important role in removing damaged proteins, organelles or cellular fragments from the cell. Under stressful conditions such as hypoxia, nutrient deficiency or chemotherapy, this process can also become the strategy for cell survival. Autophagy can be nonselective or selective in removing specific organelles, ribosomes, and protein aggregates, although the complete mechanisms that regulate aspects of selective autophagy are not fully understood. This review summarizes the most recent research into understanding the different types and mechanisms of autophagy. The relationship between apoptosis and autophagy on the level of molecular regulation of the expression of selected proteins such as p53, Bcl-2/Beclin 1, p62, Atg proteins, and caspases was discussed. Intensive studies have revealed a whole range of novel compounds with an anticancer activity that inhibit or activate regulatory pathways involved in autophagy. We focused on the presentation of compounds strongly affecting the autophagy process, with particular emphasis on those that are undergoing clinical and preclinical cancer research. Moreover, the target points, adverse effects and therapeutic schemes of autophagy inhibitors and activators are presented.
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页数:35
相关论文
共 226 条
[61]   Biological evaluation of octahydropyrazin[2,1-a:5,4-a]diisoquinoline derivatives as potent anticancer agents [J].
Gornowicz, Agnieszka ;
Pawlowska, Natalia ;
Czajkowska, Anna ;
Czarnomysy, Robert ;
Bielawska, Anna ;
Bielawski, Krzysztof ;
Michalak, Olga ;
Staszewska-Krajewska, Olga ;
Kaluza, Zbigniew .
TUMOR BIOLOGY, 2017, 39 (06)
[62]   The recognition of ubiquitinated proteins by the proteasome [J].
Grice, Guinevere L. ;
Nathan, James A. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2016, 73 (18) :3497-3506
[63]   Autophagy, Metabolism, and Cancer [J].
Guo, Jessie Yanxiang ;
White, Eileen .
TARGETING CANCER, VOL 81, 2016, 2016, 81 :73-78
[64]   Novel quinazolinone MJ-33 induces AKT/mTOR-mediated autophagy-associated apoptosis in 5FU-resistant colorectal cancer cells [J].
Ha, Hai-Anh ;
Chiang, Jo-Hua ;
Tsai, Fuu-Jen ;
Bau, Da-Tian ;
Juan, Yu-Ning ;
Lo, Yu-Hsiang ;
Hour, Mann-Jen ;
Yang, Jai-Sing .
ONCOLOGY REPORTS, 2021, 45 (02) :680-692
[65]   A Complex between Atg7 and Caspase-9 A NOVEL MECHANISM OF CROSS-REGULATION BETWEEN AUTOPHAGY AND APOPTOSIS [J].
Han, Jie ;
Hou, Wen ;
Goldstein, Leslie A. ;
Stolz, Donna B. ;
Watkins, Simon C. ;
Rabinowich, Hannah .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (10) :6485-6497
[66]   Rapamycin fed late in life extends lifespan in genetically heterogeneous mice [J].
Harrison, David E. ;
Strong, Randy ;
Sharp, Zelton Dave ;
Nelson, James F. ;
Astle, Clinton M. ;
Flurkey, Kevin ;
Nadon, Nancy L. ;
Wilkinson, J. Erby ;
Frenkel, Krystyna ;
Carter, Christy S. ;
Pahor, Marco ;
Javors, Martin A. ;
Fernandez, Elizabeth ;
Miller, Richard A. .
NATURE, 2009, 460 (7253) :392-U108
[67]   Miconazole induces protective autophagy in bladder cancer cells [J].
Ho, Chao-Yen ;
Chang, An-Chen ;
Hsu, Chung-Hua ;
Tsai, Te-Fu ;
Lin, Yi-Chia ;
Chou, Kuang-Yu ;
Chen, Hung-En ;
Lin, Ji-Fan ;
Chen, Po-Chun ;
Hwang, Thomas I-Sheng .
ENVIRONMENTAL TOXICOLOGY, 2021, 36 (02) :185-193
[68]   Effects of Metformin Versus Glipizide on Cardiovascular Outcomes in Patients With Type 2 Diabetes and Coronary Artery Disease [J].
Hong, Jie ;
Zhang, Yife ;
Lai, Shenghan ;
Lv, Ankang ;
Su, Qing ;
Dong, Yan ;
Zhou, Zhiguang ;
Tang, Weili ;
Zhao, Jajun ;
Cui, Lianqun ;
Zou, Dajin ;
Wang, Dawang ;
Li, Hong ;
Liu, Chao ;
Wu, Guoting ;
Shen, Jie ;
Zhu, Dalong ;
Wang, Weiqing ;
Shen, Weifeng ;
Ning, Guang .
DIABETES CARE, 2013, 36 (05) :1304-1311
[69]   Antitumor effects of the novel quinazolinone MJ-33: Inhibition of metastasis through the MAPK, AKT, NF-κB and AP-1 signaling pathways in DU145 human prostate cancer cells [J].
Hour, Mann-Jen ;
Tsai, Shih-Chang ;
Wu, Hsi-Chin ;
Lin, Meng-Wei ;
Chung, Jing-Gung ;
Wu, Jin-Bin ;
Chiang, Jo-Hua ;
Tsuzuki, Minoru ;
Yang, Jai-Sing .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2012, 41 (04) :1513-1519
[70]   A Novel Salicylanilide Derivative Induces Autophagy Cell Death in Castration-Resistant Prostate Cancer via ER Stress-Activated PERK Signaling Pathway [J].
Hsieh, Chia-Ling ;
Huang, Hsu-Shan ;
Chen, Kuan-Chou ;
Saka, Teigi ;
Chiang, Chih-Ying ;
Chung, Leland W. K. ;
Sung, Shian-Ying .
MOLECULAR CANCER THERAPEUTICS, 2020, 19 (01) :101-111