Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4T5SMS)

• DOT Name: Autophagy protein 5 (ATG5)
• Synonyms: APG5-like; Apoptosis-specific protein
• Gene Name: ATG5
• Related Disease:
  Glioblastoma multiforme
  Metastatic malignant neoplasm
  Alzheimer disease
  Amyotrophic lateral sclerosis
  Anemia
  Bone osteosarcoma
  Breast carcinoma
  Colorectal carcinoma
  Crohn disease
  Gastric cancer
  Hepatitis B virus infection
  Hepatitis C virus infection
  Hepatocellular carcinoma
  Melanoma
  Myositis disease
  Narcolepsy
  Neoplasm
  Non-small-cell lung cancer
  Osteosarcoma
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Plasma cell myeloma
  Prostate carcinoma
  Stomach cancer
  Systemic sclerosis
  Asthma
  Immune system disorder
  Multiple sclerosis
  Rheumatoid arthritis
  Acute myelogenous leukaemia
  Adult glioblastoma
  Ankylosing spondylitis
  Autoimmune disease
  Breast cancer
  Ischemia
  leukaemia
  Leukemia
  Myocardial infarction
  Prostate cancer
  Psoriasis
  Sclerosing cholangitis
  Spinocerebellar ataxia, autosomal recessive 25
  Ulcerative colitis
• UniProt ID: ATG5_HUMAN
• PDB ID: 4GDK; 4GDL; 4NAW; 4TQ0; 4TQ1; 5D7G; 5NPV; 5NPW; 7W36
• Pfam ID: PF20637 ; PF20638 ; PF04106
• Sequence:
  MTDDKDVLRDVWFGRIPTCFTLYQDEITEREAEPYYLLLPRVSYLTLVTDKVKKHFQKVM
  RQEDISEIWFEYEGTPLKWHYPIGLLFDLLASSSALPWNITVHFKSFPEKDLLHCPSKDA
  IEAHFMSCMKEADALKHKSQVINEMQKKDHKQLWMGLQNDRFDQFWAINRKLMEYPAEEN
  GFRYIPFRIYQTTTERPFIQKLFRPVAADGQLHTLGDLLKEVCPSAIDPEDGEKKNQVMI
  HGIEPMLETPLQWLSEHLSYPDNFLHISIIPQPTD
• Function: Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway; May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD; (Microbial infection) May act as a proviral factor. In association with ATG12, negatively regulates the innate antiviral immune response by impairing the type I IFN production pathway upon vesicular stomatitis virus (VSV) infection. Required for the translation of incoming hepatitis C virus (HCV) RNA and, thereby, for initiation of HCV replication, but not required once infection is established.
• Tissue Specificity: Ubiquitous. The mRNA is present at similar levels in viable and apoptotic cells, whereas the protein is dramatically highly expressed in apoptotic cells.
• KEGG Pathway:
  Autophagy - other (hsa04136)
  Autophagy - animal (hsa04140)
  Longevity regulating pathway (hsa04211)
  Longevity regulating pathway - multiple species (hsa04213)
  Ferroptosis (hsa04216)
  NOD-like receptor sig.ling pathway (hsa04621)
  RIG-I-like receptor sig.ling pathway (hsa04622)
  Shigellosis (hsa05131)
• Reactome Pathway:
  PINK1-PRKN Mediated Mitophagy (R-HSA-5205685)
  Receptor Mediated Mitophagy (R-HSA-8934903)
  Negative regulators of DDX58/IFIH1 signaling (R-HSA-936440)
  Macroautophagy (R-HSA-1632852)

Molecular Interaction Atlas (MIA) of This DOT

44 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Glioblastoma multiforme	DISK8246	Definitive	Altered Expression	[1]
Metastatic malignant neoplasm	DIS86UK6	Definitive	Altered Expression	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[4]
Anemia	DISTVL0C	Strong	Biomarker	[5]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Crohn disease	DIS2C5Q8	Strong	Genetic Variation	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Hepatitis B virus infection	DISLQ2XY	Strong	Genetic Variation	[11]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[12]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[11]
Melanoma	DIS1RRCY	Strong	Biomarker	[13]
Myositis disease	DISCIXF0	Strong	Genetic Variation	[14]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[15]
Neoplasm	DISZKGEW	Strong	Altered Expression	[16]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[17]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[6]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[18]
Ovarian neoplasm	DISEAFTY	Strong	Altered Expression	[18]
Parkinson disease	DISQVHKL	Strong	Biomarker	[19]
Plasma cell myeloma	DIS0DFZ0	Strong	Genetic Variation	[20]
Prostate carcinoma	DISMJPLE	Strong	Biomarker	[21]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Systemic sclerosis	DISF44L6	Strong	Genetic Variation	[14]
Asthma	DISW9QNS	moderate	Altered Expression	[22]
Immune system disorder	DISAEGPH	moderate	Genetic Variation	[23]
Multiple sclerosis	DISB2WZI	moderate	Biomarker	[24]
Rheumatoid arthritis	DISTSB4J	moderate	Genetic Variation	[25]
Acute myelogenous leukaemia	DISCSPTN	Disputed	Biomarker	[26]
Adult glioblastoma	DISVP4LU	Limited	Biomarker	[27]
Ankylosing spondylitis	DISRC6IR	Limited	Genetic Variation	[28]
Autoimmune disease	DISORMTM	Limited	Altered Expression	[29]
Breast cancer	DIS7DPX1	Limited	Genetic Variation	[7]
Ischemia	DIS5XOOY	Limited	Biomarker	[30]
leukaemia	DISS7D1V	Limited	Biomarker	[31]
Leukemia	DISNAKFL	Limited	Biomarker	[31]
Myocardial infarction	DIS655KI	Limited	Biomarker	[32]
Prostate cancer	DISF190Y	Limited	Biomarker	[21]
Psoriasis	DIS59VMN	Limited	Genetic Variation	[9]
Sclerosing cholangitis	DIS7GZNB	Limited	Genetic Variation	[9]
Spinocerebellar ataxia, autosomal recessive 25	DISDMD53	Limited	Autosomal recessive	[33]
Ulcerative colitis	DIS8K27O	Limited	Genetic Variation	[9]

This DOT Affected the Drug Response of 3 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Autophagy protein 5 (ATG5) decreases the response to substance of Cisplatin.	[74]
Amiodarone	DMUTEX3	Phase 2/3 Trial	Autophagy protein 5 (ATG5) affects the response to substance of Amiodarone.	[75]
Thenoyltrifluoroacetone	DM54OKX	Investigative	Autophagy protein 5 (ATG5) affects the response to substance of Thenoyltrifluoroacetone.	[76]

41 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Autophagy protein 5 (ATG5).	[34]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Autophagy protein 5 (ATG5).	[35]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Autophagy protein 5 (ATG5).	[36]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Autophagy protein 5 (ATG5).	[37]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Autophagy protein 5 (ATG5).	[38]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Autophagy protein 5 (ATG5).	[39]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Autophagy protein 5 (ATG5).	[40]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Autophagy protein 5 (ATG5).	[41]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Autophagy protein 5 (ATG5).	[34]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Autophagy protein 5 (ATG5).	[42]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Autophagy protein 5 (ATG5).	[43]
Menthol	DMG2KW7	Approved	Menthol increases the expression of Autophagy protein 5 (ATG5).	[44]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone decreases the expression of Autophagy protein 5 (ATG5).	[45]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Autophagy protein 5 (ATG5).	[46]
Sorafenib	DMS8IFC	Approved	Sorafenib increases the expression of Autophagy protein 5 (ATG5).	[47]
Gefitinib	DM15F0X	Approved	Gefitinib increases the expression of Autophagy protein 5 (ATG5).	[48]
Artesunate	DMR27C8	Approved	Artesunate increases the expression of Autophagy protein 5 (ATG5).	[49]
Sevoflurane	DMC9O43	Approved	Sevoflurane increases the expression of Autophagy protein 5 (ATG5).	[50]
Trovafloxacin	DM6AN32	Approved	Trovafloxacin increases the expression of Autophagy protein 5 (ATG5).	[51]
Promethazine	DM6I5GR	Approved	Promethazine decreases the expression of Autophagy protein 5 (ATG5).	[52]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Autophagy protein 5 (ATG5).	[53]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of Autophagy protein 5 (ATG5).	[54]
Chloroquine	DMSI5CB	Phase 3 Trial	Chloroquine increases the expression of Autophagy protein 5 (ATG5).	[55]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Autophagy protein 5 (ATG5).	[56]
Thymoquinone	DMVDTR2	Phase 2/3	Thymoquinone decreases the expression of Autophagy protein 5 (ATG5).	[57]
Tetrandrine	DMAOJBX	Phase 1	Tetrandrine decreases the expression of Autophagy protein 5 (ATG5).	[59]
GSK618334	DMJPXZ4	Phase 1	GSK618334 increases the expression of Autophagy protein 5 (ATG5).	[60]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 increases the expression of Autophagy protein 5 (ATG5).	[61]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Autophagy protein 5 (ATG5).	[62]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Autophagy protein 5 (ATG5).	[63]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Autophagy protein 5 (ATG5).	[64]
Glyphosate	DM0AFY7	Investigative	Glyphosate increases the expression of Autophagy protein 5 (ATG5).	[65]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal increases the expression of Autophagy protein 5 (ATG5).	[66]
Butanoic acid	DMTAJP7	Investigative	Butanoic acid increases the expression of Autophagy protein 5 (ATG5).	[67]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Autophagy protein 5 (ATG5).	[68]
CH-223191	DMMJZYC	Investigative	CH-223191 decreases the expression of Autophagy protein 5 (ATG5).	[69]
acrolein	DMAMCSR	Investigative	acrolein increases the expression of Autophagy protein 5 (ATG5).	[70]
Cordycepin	DM72Y01	Investigative	Cordycepin increases the expression of Autophagy protein 5 (ATG5).	[71]
ELLAGIC ACID	DMX8BS5	Investigative	ELLAGIC ACID increases the expression of Autophagy protein 5 (ATG5).	[53]
OLEANOLIC_ACID	DMWDMJ3	Investigative	OLEANOLIC_ACID increases the expression of Autophagy protein 5 (ATG5).	[72]
3-acetyl-11-keto-beta-boswellic acid	DMGO2D7	Investigative	3-acetyl-11-keto-beta-boswellic acid decreases the expression of Autophagy protein 5 (ATG5).	[73]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Autophagy protein 5 (ATG5).	[58]

References

• [1] Regorafenib induces lethal autophagy arrest by stabilizing PSAT1 in glioblastoma.Autophagy. 2020 Jan;16(1):106-122. doi: 10.1080/15548627.2019.1598752. Epub 2019 Apr 9.
• [2] Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice.Gastroenterology. 2019 Jan;156(1):203-217.e20. doi: 10.1053/j.gastro.2018.09.053. Epub 2018 Oct 6.
• [3] Plasma ATG5 is increased in Alzheimer's disease.Sci Rep. 2019 Mar 18;9(1):4741. doi: 10.1038/s41598-019-41347-2.
• [4] VCP maintains lysosomal homeostasis and TFEB activity in differentiated skeletal muscle.Autophagy. 2019 Jun;15(6):1082-1099. doi: 10.1080/15548627.2019.1569933. Epub 2019 Jan 29.
• [5] Autophagy limits proliferation and glycolytic metabolism in acute myeloid leukemia.Cell Death Discov. 2015 Aug 17;1:15008-. doi: 10.1038/cddiscovery.2015.8.
• [6] PCAF regulates H3 phosphorylation and promotes autophagy in osteosarcoma cells.Biomed Pharmacother. 2019 Oct;118:109395. doi: 10.1016/j.biopha.2019.109395. Epub 2019 Aug 29.
• [7] ErbB4 receptor polymorphism 2368A>C and risk of breast cancer.Breast. 2018 Dec;42:157-163. doi: 10.1016/j.breast.2018.10.002. Epub 2018 Oct 9.
• [8] miR-20a inhibits hypoxia-induced autophagy by targeting ATG5/FIP200 in colorectal cancer.Mol Carcinog. 2019 Jul;58(7):1234-1247. doi: 10.1002/mc.23006. Epub 2019 Mar 18.
• [9] Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci.Nat Genet. 2016 May;48(5):510-8. doi: 10.1038/ng.3528. Epub 2016 Mar 14.
• [10] LncRNA MALAT1 potentiates autophagyassociated cisplatin resistance by regulating the microRNA?0b/autophagyrelated gene 5 axis in gastric cancer.Int J Oncol. 2019 Jan;54(1):239-248. doi: 10.3892/ijo.2018.4609. Epub 2018 Oct 26.
• [11] Autophagy-Related 5 Gene rs510432 Polymorphism Is Associated with Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Virus Infection.Immunol Invest. 2019 May;48(4):378-391. doi: 10.1080/08820139.2019.1567532. Epub 2019 Mar 25.
• [12] Induction of selective autophagy in cells replicating hepatitis C virus genome.J Gen Virol. 2018 Dec;99(12):1643-1657. doi: 10.1099/jgv.0.001161. Epub 2018 Oct 12.
• [13] miR-216b enhances the efficacy of vemurafenib by targeting Beclin-1, UVRAG and ATG5 in melanoma.Cell Signal. 2018 Jan;42:30-43. doi: 10.1016/j.cellsig.2017.09.024. Epub 2017 Oct 2.
• [14] Genome-wide meta-analysis reveals shared new loci in systemic seropositive rheumatic diseases.Ann Rheum Dis. 2019 Mar;78(3):311-319. doi: 10.1136/annrheumdis-2018-214127. Epub 2018 Dec 20.
• [15] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [16] Expression analysis of NF-B interacting long noncoding RNAs in breast cancer.Exp Mol Pathol. 2020 Feb;112:104359. doi: 10.1016/j.yexmp.2019.104359. Epub 2019 Dec 14.
• [17] MiRNA-153-3p promotes gefitinib-sensitivity in non-small cell lung cancer by inhibiting ATG5 expression and autophagy.Eur Rev Med Pharmacol Sci. 2019 Mar;23(6):2444-2452. doi: 10.26355/eurrev_201903_17391.
• [18] The levels of mutant K-RAS and mutant N-RAS are rapidly reduced in a Beclin1 / ATG5 -dependent fashion by the irreversible ERBB1/2/4 inhibitor neratinib.Cancer Biol Ther. 2018 Feb 1;19(2):132-137. doi: 10.1080/15384047.2017.1394556. Epub 2017 Dec 8.
• [19] The lysosomal membrane protein LAMP2A promotes autophagic flux and prevents SNCA-induced Parkinson disease-like symptoms in the Drosophila brain.Autophagy. 2018;14(11):1898-1910. doi: 10.1080/15548627.2018.1491489. Epub 2018 Aug 10.
• [20] Genome-wide association study identifies multiple susceptibility loci for multiple myeloma.Nat Commun. 2016 Jul 1;7:12050. doi: 10.1038/ncomms12050.
• [21] PAX5-induced upregulation of IDH1-AS1 promotes tumor growth in prostate cancer by regulating ATG5-mediated autophagy.Cell Death Dis. 2019 Sep 30;10(10):734. doi: 10.1038/s41419-019-1932-3.
• [22] MicroRNA-30a Targets ATG5 and Attenuates Airway Fibrosis in Asthma by Suppressing Autophagy.Inflammation. 2020 Feb;43(1):44-53. doi: 10.1007/s10753-019-01076-0.
• [23] Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.PLoS Genet. 2011 Feb;7(2):e1002004. doi: 10.1371/journal.pgen.1002004. Epub 2011 Feb 24.
• [24] Correlation between auto/mitophagic processes and magnetic resonance imaging activity in multiple sclerosis patients.J Neuroinflammation. 2019 Jun 27;16(1):131. doi: 10.1186/s12974-019-1526-0.
• [25] Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.Hum Mol Genet. 2019 Mar 1;28(5):858-874. doi: 10.1093/hmg/ddy395.
• [26] Inhibition of autophagy as a treatment strategy for p53 wild-type acute myeloid leukemia.Cell Death Dis. 2017 Jul 13;8(7):e2927. doi: 10.1038/cddis.2017.317.
• [27] The HIF?/miR?24?p/ATG5 axis affects cell mobility and chemosensitivity by regulating hypoxiainduced protective autophagy in glioblastoma and astrocytoma.Oncol Rep. 2019 Mar;41(3):1759-1768. doi: 10.3892/or.2018.6929. Epub 2018 Dec 13.
• [28] High rates of tuberculin skin test positivity due to methotrexate therapy: False positive results?.Semin Arthritis Rheum. 2018 Dec;48(3):538-546. doi: 10.1016/j.semarthrit.2018.03.018. Epub 2018 Mar 29.
• [29] Rare Variants of ATG5 Are Likely to Be Associated With Chinese Patients With Systemic Lupus Erythematosus.Medicine (Baltimore). 2015 Jun;94(22):e939. doi: 10.1097/MD.0000000000000939.
• [30] Cold ischemia-induced autophagy in rat lung tissue.Mol Med Rep. 2015 Apr;11(4):2513-9. doi: 10.3892/mmr.2014.2999. Epub 2014 Nov 26.
• [31] Growth inhibitory and proapoptotic effects of l-asparaginase from Fusarium culmorum ASP-87 on human leukemia cells (Jurkat).Fundam Clin Pharmacol. 2017 Jun;31(3):292-300. doi: 10.1111/fcp.12257. Epub 2016 Dec 30.
• [32] p27kip1 haploinsufficiency preserves myocardial function in the early stages of myocardial infarction via Atg5mediated autophagy flux restoration.Mol Med Rep. 2019 Oct;20(4):3840-3848. doi: 10.3892/mmr.2019.10632. Epub 2019 Sep 2.
• [33] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [34] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [35] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [36] Low Autophagy (ATG) Gene Expression Is Associated with an Immature AML Blast Cell Phenotype and Can Be Restored during AML Differentiation Therapy. Oxid Med Cell Longev. 2018 Mar 18;2018:1482795. doi: 10.1155/2018/1482795. eCollection 2018.
• [37] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [38] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [39] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [40] Arsenic trioxide induces autophagic cell death in osteosarcoma cells via the ROS-TFEB signaling pathway. Biochem Biophys Res Commun. 2018 Jan 29;496(1):167-175. doi: 10.1016/j.bbrc.2018.01.018. Epub 2018 Jan 4.
• [41] Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin. Cell Host Microbe. 2009 Sep 17;6(3):231-43. doi: 10.1016/j.chom.2009.08.004.
• [42] Inhibition of autophagy enhances Hydroquinone-induced TK6 cell death. Toxicol In Vitro. 2017 Jun;41:123-132. doi: 10.1016/j.tiv.2017.02.024. Epub 2017 Mar 2.
• [43] Modulation of Atg5 expression by globular adiponectin contributes to autophagy flux and suppression of ethanol-induced cell death in liver cells. Food Chem Toxicol. 2014 Jun;68:11-22. doi: 10.1016/j.fct.2014.02.027. Epub 2014 Feb 27.
• [44] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [45] Autophagy (but not metabolism) is a key event in mitoxantrone-induced cytotoxicity in differentiated AC16 cardiac cells. Arch Toxicol. 2023 Jan;97(1):201-216. doi: 10.1007/s00204-022-03363-6. Epub 2022 Oct 10.
• [46] Role of autophagy in chemoresistance: regulation of the ATM-mediated DNA-damage signaling pathway through activation of DNA-PKcs and PARP-1. Biochem Pharmacol. 2012 Mar 15;83(6):747-57. doi: 10.1016/j.bcp.2011.12.029. Epub 2011 Dec 29.
• [47] Vorinostat and sorafenib increase ER stress, autophagy and apoptosis via ceramide-dependent CD95 and PERK activation. Cancer Biol Ther. 2008 Oct;7(10):1648-62. doi: 10.4161/cbt.7.10.6623. Epub 2008 Oct 12.
• [48] EGFR tyrosine kinase inhibitors activate autophagy as a cytoprotective response in human lung cancer cells. PLoS One. 2011;6(6):e18691. doi: 10.1371/journal.pone.0018691. Epub 2011 Jun 2.
• [49] Artesunate alleviates liver fibrosis by regulating ferroptosis signaling pathway. Biomed Pharmacother. 2019 Jan;109:2043-2053. doi: 10.1016/j.biopha.2018.11.030. Epub 2018 Nov 26.
• [50] 4.8% sevoflurane induces activation of autophagy in human neuroblastoma SH-SY5Y cells by the AMPK/mTOR signaling pathway. Neurotoxicology. 2022 May;90:256-264. doi: 10.1016/j.neuro.2022.04.008. Epub 2022 Apr 23.
• [51] TNF enhances trovafloxacin-induced in vitro hepatotoxicity by inhibiting protective autophagy. Toxicol Lett. 2021 May 15;342:73-84. doi: 10.1016/j.toxlet.2021.02.009. Epub 2021 Feb 17.
• [52] AMPK activation induced by promethazine increases NOXA expression and Beclin-1 phosphorylation and drives autophagy-associated apoptosis in chronic myeloid leukemia. Chem Biol Interact. 2020 Jan 5;315:108888. doi: 10.1016/j.cbi.2019.108888. Epub 2019 Nov 2.
• [53] Interactive gene expression pattern in prostate cancer cells exposed to phenolic antioxidants. Life Sci. 2002 Mar 1;70(15):1821-39.
• [54] Inhibition of ATF4-mediated elevation of both autophagy and AKT/mTOR was involved in antitumorigenic activity of curcumin. Food Chem Toxicol. 2023 Mar;173:113609. doi: 10.1016/j.fct.2023.113609. Epub 2023 Jan 12.
• [55] Chloroquine aggravates the arsenic trioxide (As2O3)-induced apoptosis of acute promyelocytic leukemia NB4 cells via inhibiting lysosomal degradation in vitro. Eur Rev Med Pharmacol Sci. 2018 Oct;22(19):6412-6421. doi: 10.26355/eurrev_201810_16054.
• [56] Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. Neoplasia. 2004 Jul-Aug;6(4):354-63. doi: 10.1593/neo.03478.
• [57] Thymoquinone suppresses the proliferation of renal cell carcinoma cells via reactive oxygen species-induced apoptosis and reduces cell stemness. Environ Toxicol. 2019 Nov;34(11):1208-1220. doi: 10.1002/tox.22822. Epub 2019 Jul 12.
• [58] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [59] Tetrandrine induces apoptosis Via caspase-8, -9, and -3 and poly (ADP ribose) polymerase dependent pathways and autophagy through beclin-1/ LC3-I, II signaling pathways in human oral cancer HSC-3 cells. Environ Toxicol. 2016 Apr;31(4):395-406. doi: 10.1002/tox.22053. Epub 2014 Sep 30.
• [60] FTY720 induces autophagy-related apoptosis and necroptosis in human glioblastoma cells. Toxicol Lett. 2015 Jul 2;236(1):43-59. doi: 10.1016/j.toxlet.2015.04.015. Epub 2015 May 1.
• [61] Antitumor activity of luteolin in human colon cancer SW620 cells is mediated by the ERK/FOXO3a signaling pathway. Toxicol In Vitro. 2020 Aug;66:104852. doi: 10.1016/j.tiv.2020.104852. Epub 2020 Apr 5.
• [62] Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells. Toxicol Appl Pharmacol. 2010 Oct 15;248(2):111-21.
• [63] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [64] [The effect of paraquat on autophagy in human embryonic neural progenitor cells]. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi. 2016 Mar 20;34(3):178-83. doi: 10.3760/cma.j.issn.1001-9391.2016.03.005.
• [65] Use of human neuroblastoma SH-SY5Y cells to evaluate glyphosate-induced effects on oxidative stress, neuronal development and cell death signaling pathways. Environ Int. 2020 Feb;135:105414. doi: 10.1016/j.envint.2019.105414. Epub 2019 Dec 23.
• [66] Upregulation of the TFEB-mediated lysosome function relieves 4-Hydroxynonenal-Induced apoptosis. Chem Biol Interact. 2022 Aug 1;362:109963. doi: 10.1016/j.cbi.2022.109963. Epub 2022 May 9.
• [67] Oxidative stress plays a key role in butyrate-mediated autophagy via Akt/mTOR pathway in hepatoma cells. Chem Biol Interact. 2017 Aug 1;273:99-106. doi: 10.1016/j.cbi.2017.06.001. Epub 2017 Jun 12.
• [68] Resveratrol relieves particulate matter (mean diameter < 2.5 m)-induced oxidative injury of lung cells through attenuation of autophagy deregulation. J Appl Toxicol. 2018 Sep;38(9):1251-1261. doi: 10.1002/jat.3636. Epub 2018 May 20.
• [69] Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands. Toxicol Lett. 2018 Aug;292:162-174.
• [70] Acrolein induces NLRP3 inflammasome-mediated pyroptosis and suppresses migration via ROS-dependent autophagy in vascular endothelial cells. Toxicology. 2018 Dec 1;410:26-40. doi: 10.1016/j.tox.2018.09.002. Epub 2018 Sep 8.
• [71] Cordycepin Enhances SIRT1 Expression and Maintains Stemness of Human Mesenchymal Stem Cells. In Vivo. 2023 Mar-Apr;37(2):596-610. doi: 10.21873/invivo.13118.
• [72] SZC015, a synthetic oleanolic acid derivative, induces both apoptosis and autophagy in MCF-7 breast cancer cells. Chem Biol Interact. 2016 Jan 25;244:94-104. doi: 10.1016/j.cbi.2015.11.013. Epub 2015 Nov 21.
• [73] Acetyl-11-keto--boswellic acid enhances the cisplatin sensitivity of non-small cell lung cancer cells through cell cycle arrest, apoptosis induction, and autophagy suppression via p21-dependent signaling pathway. Cell Biol Toxicol. 2021 Apr;37(2):209-228. doi: 10.1007/s10565-020-09541-5. Epub 2020 Jun 20.
• [74] Concomitant inhibition of AKT and autophagy is required for efficient cisplatin-induced apoptosis of metastatic skin carcinoma. Int J Cancer. 2010 Dec 15;127(12):2790-803. doi: 10.1002/ijc.25300.
• [75] Autophagy alleviates amiodarone-induced hepatotoxicity. Arch Toxicol. 2020 Oct;94(10):3527-3539. doi: 10.1007/s00204-020-02837-9. Epub 2020 Jul 10.
• [76] Mitochondrial electron-transport-chain inhibitors of complexes I and II induce autophagic cell death mediated by reactive oxygen species. J Cell Sci. 2007 Dec 1;120(Pt 23):4155-66. doi: 10.1242/jcs.011163.