Autophagy as a molecular target for cancer treatment

被引:302
作者
Kocaturk, Nur Mehpare [1 ]
Akkoc, Yunus [2 ]
Kig, Cenk [3 ]
Bayraktar, Oznur [4 ]
Gozuacik, Devrim [1 ,2 ]
Kutlu, Ozlem [1 ]
机构
[1] Sabanci Univ, Nanotechnol Res & Applicat Ctr SUNUM, Orta Mah Univ Cad 27, TR-34956 Istanbul, Turkey
[2] Sabanci Univ, Mol Biol Genet & Bioengn Program, Fac Engn & Nat Sci, TR-34956 Istanbul, Turkey
[3] Istanbul Yeni Yuzyil Univ, Fac Med, TR-34010 Istanbul, Turkey
[4] Okan Univ, Dept Med Biol & Genet, Fac Med, Istanbul, Turkey
关键词
Autophagy; Cancer; Therapeutic agents; ENDOPLASMIC-RETICULUM STRESS; STARVATION-INDUCED AUTOPHAGY; TYROSINE KINASE INHIBITOR; HYPOXIA-INDUCIBLE FACTORS; CELL-DEATH; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; HISTONE DEACETYLASE; MAMMALIAN TARGET; COLON-CANCER;
D O I
10.1016/j.ejps.2019.04.011
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Autophagy is an evolutionarily conserved catabolic mechanism, by which eukaryotic cells recycle or degrades internal constituents through membrane-trafficking pathway. Thus, autophagy provides the cells with a sustainable source of biomolecules and energy for the maintenance of homeostasis under stressful conditions such as tumor microenvironment. Recent findings revealed a close relationship between autophagy and malignant transformation. However, due to the complex dual role of autophagy in tumor survival or cell death, efforts to develop efficient treatment strategies targeting the autophagy/cancer relation have largely been unsuccessful. Here we review the two-faced role of autophagy in cancer as a tumor suppressor or as a pro-oncogenic mechanism. In this sense, we also review the shared regulatory pathways that play a role in autophagy and malignant transformation. Finally, anti-cancer therapeutic agents used as either inhibitors or inducers of autophagy have been discussed.
引用
收藏
页码:116 / 137
页数:22
相关论文
共 395 条
[1]   Autophagy delays apoptotic death in breast cancer cells following DNA damage [J].
Abedin, M. J. ;
Wang, D. ;
McDonnell, M. A. ;
Lehmann, U. ;
Kelekar, A. .
CELL DEATH AND DIFFERENTIATION, 2007, 14 (03) :500-510
[2]   Doxorubicin Plus Sorafenib vs Doxorubicin Alone in Patients With Advanced Hepatocellular Carcinoma A Randomized Trial [J].
Abou-Alfa, Ghassan K. ;
Johnson, Philip ;
Knox, Jennifer J. ;
Capanu, Marinela ;
Davidenko, Irina ;
Lacava, Juan ;
Leung, Thomas ;
Gansukh, Bolorsukh ;
Saltz, Leonard B. .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2010, 304 (19) :2154-2160
[3]   Bcl-2 and the outer mitochondrial membrane in the inactivation of cytochrome c during fas-mediated apoptosis [J].
Adachi, S ;
Cross, AR ;
Babior, BM ;
Gottlieb, RA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (35) :21878-21882
[4]   Synergistic combination therapy with nanoliposomal C6-ceramide and vinblastine is associated with autophagy dysfunction in hepatocarcinoma and colorectal cancer models [J].
Adiseshaiah, Pavan P. ;
Clogston, Jeffrey D. ;
McLeland, Christopher B. ;
Rodriguez, Jamie ;
Potter, Timothy M. ;
Neun, Barry W. ;
Skoczen, Sarah L. ;
Shanmugavelandy, Sriram S. ;
Kester, Mark ;
Stern, Stephan T. ;
McNeil, Scott E. .
CANCER LETTERS, 2013, 337 (02) :254-265
[5]   Expression of beclin-1, an autophagy-related protein, in gastric and colorectal cancers [J].
Ahn, Chang Hyeok ;
Jeong, Eun Goo ;
Lee, Jong Woo ;
Kim, Min Sung ;
Kim, Sung Hee ;
Kim, Sung Soo ;
Yoo, Nam Jin ;
Lee, Sug Hyung .
APMIS, 2007, 115 (12) :1344-1349
[6]   Silencing of Bcl-2 expression by small interfering RNA induces autophagic cell death in MCF-7 breast cancer cells [J].
Akar, Ugur ;
Chaves-Reyez, Arturo ;
Barria, Magaly ;
Tari, Ana ;
Sanguino, Angela ;
Kondo, Yasuko ;
Kondo, Seiji ;
Arun, Banu ;
Lopez-Berestein, Gabriel ;
Ozpolat, Bulent .
AUTOPHAGY, 2008, 4 (05) :669-679
[7]   Inhibition of PI3K signaling triggered apoptotic potential of curcumin which is hindered by Bcl-2 through activation of autophagy in MCF-7 cells [J].
Akkoc, Yunus ;
Berrak, Ozge ;
Arisan, Elif Damla ;
Obakan, Pinar ;
Coker-Gurkan, Ajda ;
Palavan-Unsal, Narcin .
BIOMEDICINE & PHARMACOTHERAPY, 2015, 71 :161-171
[8]   ATM engages the TSC2/mTORC1 signaling node to regulate autophagy [J].
Alexander, Angela ;
Kim, Jinhee ;
Walker, Cheryl L. .
AUTOPHAGY, 2010, 6 (05) :672-673
[9]   Metabolic Stress in Autophagy and Cell Death Pathways [J].
Altman, Brian J. ;
Rathmell, Jeffrey C. .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2012, 4 (09)
[10]   Mutational and expressional analyses of ATG5, an autophagy-related gene, in gastrointestinal cancers [J].
An, Chang Hyeok ;
Kim, Min Sung ;
Yoo, Nam Jin ;
Park, Sang Wook ;
Lee, Sug Hyung .
PATHOLOGY RESEARCH AND PRACTICE, 2011, 207 (07) :433-437