Details of Drug Off-Target (DOT)

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

• DOT Name: Cytochrome c oxidase subunit 2 (COX2)
• Synonyms: EC 7.1.1.9; Cytochrome c oxidase polypeptide II
• Gene Name: COX2
• Related Disease:
  Epithelial ovarian cancer
  Migraine disorder
  Ovarian cancer
  Ovarian neoplasm
  Anxiety
  Aortic aneurysm
  Arteriosclerosis
  Atherosclerosis
  Barrett esophagus
  Bladder cancer
  Colorectal adenoma
  Colorectal neoplasm
  Cytochrome-c oxidase deficiency disease
  Dystonia
  Familial adenomatous polyposis
  Gastric cancer
  Glioblastoma multiforme
  Glioma
  Head-neck squamous cell carcinoma
  Melanoma
  MELAS syndrome
  Mitochondrial myopathy
  Myopathy
  Nasopharyngeal carcinoma
  Non-insulin dependent diabetes
  Osteoarthritis
  Pancreatic cancer
  Polyp
  Rheumatoid arthritis
  Sensorineural hearing loss disorder
  Stomach cancer
  Type-1 diabetes
  Urinary bladder cancer
  Urinary bladder neoplasm
  Congestive heart failure
  Endometriosis
  Esophageal adenocarcinoma
  Type-1/2 diabetes
  Bone osteosarcoma
  Carcinoma
  Dementia
  Endometrial carcinoma
  Esophageal squamous cell carcinoma
  Hypothyroidism
  Mitochondrial disease
  Nephrotic syndrome
  Neuroblastoma
  Osteosarcoma
• UniProt ID: COX2_HUMAN
• PDB ID: 3VRJ; 5Z62
• EC Number: 7.1.1.9
• Pfam ID: PF00116 ; PF02790
• Sequence:
  MAHAAQVGLQDATSPIMEELITFHDHALMIIFLICFLVLYALFLTLTTKLTNTNISDAQE
  METVWTILPAIILVLIALPSLRILYMTDEVNDPSLTIKSIGHQWYWTYEYTDYGGLIFNS
  YMLPPLFLEPGDLRLLDVDNRVVLPIEAPIRMMITSQDVLHSWAVPTLGLKTDAIPGRLN
  QTTFTATRPGVYYGQCSEICGANHSFMPIVLELIPLKIFEMGPVFTL
• Function: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
• KEGG Pathway:
  Oxidative phosphorylation (hsa00190)
  Metabolic pathways (hsa01100)
  Cardiac muscle contraction (hsa04260)
  Thermogenesis (hsa04714)
  Non-alcoholic fatty liver disease (hsa04932)
  Alzheimer disease (hsa05010)
  Parkinson disease (hsa05012)
  Amyotrophic lateral sclerosis (hsa05014)
  Huntington disease (hsa05016)
  Prion disease (hsa05020)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Chemical carcinogenesis - reactive oxygen species (hsa05208)
  Diabetic cardiomyopathy (hsa05415)
• Reactome Pathway:
  Respiratory electron transport (R-HSA-611105)
  Cytoprotection by HMOX1 (R-HSA-9707564)
  TP53 Regulates Metabolic Genes (R-HSA-5628897)
• BioCyc Pathway: MetaCyc:HS00027-MONOMER

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epithelial ovarian cancer	DIS56MH2	Definitive	Biomarker	[1]
Migraine disorder	DISFCQTG	Definitive	Genetic Variation	[2]
Ovarian cancer	DISZJHAP	Definitive	Biomarker	[1]
Ovarian neoplasm	DISEAFTY	Definitive	Biomarker	[1]
Anxiety	DISIJDBA	Strong	Biomarker	[3]
Aortic aneurysm	DISQ5KRA	Strong	Altered Expression	[4]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[5]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[5]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[6]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[7]
Colorectal adenoma	DISTSVHM	Strong	Altered Expression	[8]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[9]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Strong	Biomarker	[10]
Dystonia	DISJLFGW	Strong	Biomarker	[11]
Familial adenomatous polyposis	DISW53RE	Strong	Altered Expression	[12]
Gastric cancer	DISXGOUK	Strong	Biomarker	[13]
Glioblastoma multiforme	DISK8246	Strong	Biomarker	[14]
Glioma	DIS5RPEH	Strong	Biomarker	[15]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Biomarker	[16]
Melanoma	DIS1RRCY	Strong	Biomarker	[17]
MELAS syndrome	DIS81Z3S	Strong	GermlineCausalMutation	[18]
Mitochondrial myopathy	DIS9SA7V	Strong	Genetic Variation	[19]
Myopathy	DISOWG27	Strong	Genetic Variation	[20]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Genetic Variation	[21]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[22]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[23]
Pancreatic cancer	DISJC981	Strong	Biomarker	[24]
Polyp	DISRSLYF	Strong	Biomarker	[25]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[26]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Biomarker	[27]
Stomach cancer	DISKIJSX	Strong	Biomarker	[13]
Type-1 diabetes	DIS7HLUB	Strong	Altered Expression	[28]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[7]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[7]
Congestive heart failure	DIS32MEA	moderate	Biomarker	[29]
Endometriosis	DISX1AG8	moderate	Altered Expression	[30]
Esophageal adenocarcinoma	DISODWFP	moderate	Altered Expression	[31]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[32]
Bone osteosarcoma	DIST1004	Limited	Altered Expression	[33]
Carcinoma	DISH9F1N	Limited	Altered Expression	[34]
Dementia	DISXL1WY	Limited	Genetic Variation	[35]
Endometrial carcinoma	DISXR5CY	Limited	Altered Expression	[36]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Biomarker	[37]
Hypothyroidism	DISR0H6D	Limited	Biomarker	[38]
Mitochondrial disease	DISKAHA3	Limited	Genetic Variation	[39]
Nephrotic syndrome	DISSPSC2	Limited	Genetic Variation	[40]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[41]
Osteosarcoma	DISLQ7E2	Limited	Altered Expression	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cytochrome c oxidase subunit 2 (COX2).	[42]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the activity of Cytochrome c oxidase subunit 2 (COX2).	[43]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[44]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[45]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Cytochrome c oxidase subunit 2 (COX2).	[46]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[47]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[48]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[49]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[50]
Zidovudine	DM4KI7O	Approved	Zidovudine increases the expression of Cytochrome c oxidase subunit 2 (COX2).	[51]
Bexarotene	DMOBIKY	Approved	Bexarotene decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[52]
Josamycin	DMKJ8LB	Approved	Josamycin decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[53]
Mitotane	DMU1GX0	Approved	Mitotane decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[54]
Chloramphenicol	DMFXEWT	Approved	Chloramphenicol decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[53]
Clarithromycin	DM4M1SG	Approved	Clarithromycin decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[53]
Didanosine	DMI2QPE	Approved	Didanosine decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[55]
Telbivudine	DMSWUGE	Approved	Telbivudine decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[56]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Cytochrome c oxidase subunit 2 (COX2).	[57]
Fialuridine	DMCIGRB	Phase 2	Fialuridine decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[58]
INX-189	DMSTJ6Q	Phase 2	INX-189 decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[59]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[60]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[61]
Paraquat	DMR8O3X	Investigative	Paraquat increases the expression of Cytochrome c oxidase subunit 2 (COX2).	[62]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of Cytochrome c oxidase subunit 2 (COX2).	[63]
Okadaic acid	DM47CO1	Investigative	Okadaic acid affects the expression of Cytochrome c oxidase subunit 2 (COX2).	[64]
Ethidium	DMMEQUR	Investigative	Ethidium decreases the expression of Cytochrome c oxidase subunit 2 (COX2).	[65]
Oxalacetic acid	DMPZSV1	Investigative	Oxalacetic acid increases the expression of Cytochrome c oxidase subunit 2 (COX2).	[63]

References

• [1] Suppression of chemotherapy-induced cytokine/lipid mediator surge and ovarian cancer by a dual COX-2/sEH inhibitor.Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1698-1703. doi: 10.1073/pnas.1803999116. Epub 2019 Jan 15.
• [2] Cox-2 gene variants in migraine.Gene. 2013 Apr 15;518(2):292-5. doi: 10.1016/j.gene.2012.12.110. Epub 2013 Jan 26.
• [3] Mitochondrial Gene Expression Profiles Are Associated with Maternal Psychosocial Stress in Pregnancy and Infant Temperament.PLoS One. 2015 Sep 29;10(9):e0138929. doi: 10.1371/journal.pone.0138929. eCollection 2015.
• [4] Hepatic injury induced by thioacetamide causes aortic endothelial dysfunction by a cyclooxygenase-dependent mechanism.Life Sci. 2018 Nov 1;212:168-175. doi: 10.1016/j.lfs.2018.09.051. Epub 2018 Oct 4.
• [5] Celecoxib aggravates atherogenesis and upregulates leukotrienes in ApoE(-/-) mice and lipopolysaccharide-stimulated RAW264.7 macrophages.Atherosclerosis. 2019 May;284:50-58. doi: 10.1016/j.atherosclerosis.2019.02.017. Epub 2019 Mar 1.
• [6] Toll-like receptor 4 activation in Barrett's esophagus results in a strong increase in COX-2 expression.J Gastroenterol. 2014 Jul;49(7):1121-34. doi: 10.1007/s00535-013-0862-6. Epub 2013 Aug 17.
• [7] Detection of tyrosine kinase inhibitors-induced COX-2 expression in bladder cancer by fluorocoxib A.Oncotarget. 2019 Aug 27;10(50):5168-5180. doi: 10.18632/oncotarget.27125. eCollection 2019 Aug 27.
• [8] The expression and significance of feces cyclooxygensae-2 mRNA in colorectal cancer and colorectal adenomas.Saudi J Gastroenterol. 2017 Jan-Feb;23(1):28-33. doi: 10.4103/1319-3767.199112.
• [9] Risks of colorectal neoplasms and cardiovascular thromboembolic events after the combined use of selective COX-2 inhibitors and aspirin with 5-year follow-up: a meta-analysis.Colorectal Dis. 2019 Apr;21(4):417-426. doi: 10.1111/codi.14556. Epub 2019 Feb 7.
• [10] Cooperation between COA6 and SCO2 in COX2 maturation during cytochrome c oxidase assembly links two mitochondrial cardiomyopathies.Cell Metab. 2015 Jun 2;21(6):823-33. doi: 10.1016/j.cmet.2015.04.012. Epub 2015 May 7.
• [11] Human mitochondrial cytochrome c oxidase assembly factor COX18 acts transiently as a membrane insertase within the subunit 2 maturation module.J Biol Chem. 2017 May 12;292(19):7774-7783. doi: 10.1074/jbc.M117.778514. Epub 2017 Mar 22.
• [12] Inactivation of Adenomatous Polyposis Coli Reduces Bile Acid/Farnesoid X Receptor Expression through Fxr gene CpG Methylation in Mouse Colon Tumors and Human Colon Cancer Cells.J Nutr. 2016 Feb;146(2):236-42. doi: 10.3945/jn.115.216580. Epub 2015 Nov 25.
• [13] Correlation of COX-2 and MMP-13 expressions with gastric cancer and their effects on prognosis.J BUON. 2019 Jan-Feb;24(1):187-193.
• [14] A drug combination targeting hypoxia induced chemoresistance and stemness in glioma cells.Oncotarget. 2018 Apr 6;9(26):18351-18366. doi: 10.18632/oncotarget.24839. eCollection 2018 Apr 6.
• [15] miR-26b Mimic Inhibits Glioma Proliferation In Vitro and In Vivo Suppressing COX-2 Expression. Oncol Res. 2019 Feb 5;27(2):147-155.
• [16] COX-2 Docking Structural Analysis with Phytochemical Extracts of Rosemary: A Possible Cytotoxicity on Head and Neck Squamous Cell Carcinoma Cell Line (HEp-2).Anticancer Agents Med Chem. 2019;19(12):1473-1480. doi: 10.2174/1871520619666190618121706.
• [17] Anti-metastatic Properties of Naproxen-HBTA in a Murine Model of Cutaneous Melanoma.Front Pharmacol. 2019 Feb 8;10:66. doi: 10.3389/fphar.2019.00066. eCollection 2019.
• [18] Isolated cytochrome c oxidase deficiency as a cause of MELAS.J Med Genet. 2008 Feb;45(2):117-21. doi: 10.1136/jmg.2007.052076.
• [19] A novel MT-CO2 m.8249G>A pathogenic variation and the MT-TW m.5521G>A mutation in patients with mitochondrial myopathy.Mitochondrial DNA. 2014 Oct;25(5):394-9. doi: 10.3109/19401736.2013.803086. Epub 2013 Jul 10.
• [20] Mitochondrial complex IV deficiency caused by a novel frameshift variant in MT-CO2 associated with myopathy and perturbed acylcarnitine profile.Eur J Hum Genet. 2019 Feb;27(2):331-335. doi: 10.1038/s41431-018-0286-0. Epub 2018 Oct 12.
• [21] Correlation between COX-2 gene polymorphism and susceptibility to nasopharyngeal carcinoma.Eur Rev Med Pharmacol Sci. 2019 Jul;23(13):5770-5778. doi: 10.26355/eurrev_201907_18315.
• [22] Inhibition of COX2/PGD2-Related Autophagy Is Involved in the Mechanism of Brain Injury in T2DM Rat.Front Cell Neurosci. 2019 Feb 27;13:68. doi: 10.3389/fncel.2019.00068. eCollection 2019.
• [23] Osthole ameliorates cartilage degradation by downregulation of NF-B and HIF-2 pathways in an osteoarthritis murine model.Eur J Pharmacol. 2020 Jan 15;867:172799. doi: 10.1016/j.ejphar.2019.172799. Epub 2019 Nov 22.
• [24] Breaking barriers for T cells by targeting the EPHA2/TGF-/COX-2 axis in pancreatic cancer.J Clin Invest. 2019 Jul 29;129(9):3521-3523. doi: 10.1172/JCI130316. eCollection 2019 Jul 29.
• [25] Stromal iodothyronine deiodinase 2 (DIO2) promotes the growth of intestinal tumors in Apc(716) mutant mice.Cancer Sci. 2019 Aug;110(8):2520-2528. doi: 10.1111/cas.14100. Epub 2019 Jul 7.
• [26] Selenium Nanoparticles Dispersed in Phytochemical Exert Anti-Inflammatory Activity by Modulating Catalase, GPx1, and COX-2 Gene Expression in a Rheumatoid Arthritis Rat Model.Med Sci Monit. 2019 Feb 5;25:991-1000. doi: 10.12659/MSM.912545.
• [27] Chemopreventative celecoxib fails to prevent schwannoma formation or sensorineural hearing loss in genetically engineered murine model of neurofibromatosis type 2.Oncotarget. 2017 Oct 24;9(1):718-725. doi: 10.18632/oncotarget.22002. eCollection 2018 Jan 2.
• [28] Deletion of Protein Tyrosine Phosphatase 1B (PTP1B) Enhances Endothelial Cyclooxygenase 2 Expression and Protects Mice from Type 1 Diabetes-Induced Endothelial Dysfunction.PLoS One. 2015 May 14;10(5):e0126866. doi: 10.1371/journal.pone.0126866. eCollection 2015.
• [29] The cyclooxygenase-1/mPGES-1/endothelial prostaglandin EP4 receptor pathway constrains myocardial ischemia-reperfusion injury.Nat Commun. 2019 Apr 23;10(1):1888. doi: 10.1038/s41467-019-09492-4.
• [30] Identification of differentially expressed proteins associated with recurrence in ovarian endometriotic cysts.Syst Biol Reprod Med. 2020 Feb;66(1):59-69. doi: 10.1080/19396368.2019.1688425. Epub 2019 Nov 12.
• [31] Cyclo-oxygenase-2 expression is associated with mean standardised uptake value on 18F-Fluorodeoxyglucose positron emission tomography in oesophageal adenocarcinoma.Br J Radiol. 2019 Jul;92(1099):20180668. doi: 10.1259/bjr.20180668. Epub 2019 May 8.
• [32] Combination of COX-2 inhibitor and metformin attenuates rate of admission in patients with rheumatoid arthritis and diabetes in Taiwan.Medicine (Baltimore). 2019 Oct;98(41):e17371. doi: 10.1097/MD.0000000000017371.
• [33] Cyclooxygenase-2 expression correlates with development, progression, metastasis, and prognosis of osteosarcoma: a meta-analysis and trial sequential analysis.FEBS Open Bio. 2019 Jan 7;9(2):226-240. doi: 10.1002/2211-5463.12560. eCollection 2019 Feb.
• [34] Expression of cyclooxygenase-2 has no impact on survival in adenocarcinoma of the esophagogastric junction but is associated with favourable clinicopathologic features.Histol Histopathol. 2017 Jul;32(7):735-741. doi: 10.14670/HH-11-843. Epub 2016 Nov 17.
• [35] Inhibition of cyclooxygenase as potential novel therapeutic strategy in N141I presenilin-2 familial Alzheimer's disease. Mol Psychiatry. 2006 Feb;11(2):172-81. doi: 10.1038/sj.mp.4001773.
• [36] Variances in the Level of COX-2 and iNOS in Different Grades of Endometrial Cancer.Curr Pharm Biotechnol. 2020;21(1):52-59. doi: 10.2174/1389201020666190918104105.
• [37] Role of ALDH1 in the prognosis of esophageal cancer and its relationship with tumor microenvironment.Mol Carcinog. 2018 Jan;57(1):78-88. doi: 10.1002/mc.22733. Epub 2017 Oct 9.
• [38] Hypothyroidism increases cyclooxygenase-2 levels and pro-inflammatory response and decreases cell proliferation and neuroblast differentiation in the hippocampus.Mol Med Rep. 2018 Apr;17(4):5782-5788. doi: 10.3892/mmr.2018.8605. Epub 2018 Feb 13.
• [39] Case report: a novel frameshift mutation in the mitochondrial cytochrome c oxidase II gene causing mitochondrial disorder.BMC Neurol. 2017 May 18;17(1):96. doi: 10.1186/s12883-017-0883-5.
• [40] Risk of Nephrotic Syndrome for Non-Steroidal Anti-Inflammatory Drug Users.Clin J Am Soc Nephrol. 2019 Sep 6;14(9):1355-1362. doi: 10.2215/CJN.14331218. Epub 2019 Aug 15.
• [41] Silencing the ACAT1 Gene in Human SH-SY5Y Neuroblastoma Cells Inhibits the Expression of Cyclo-Oxygenase 2 (COX2) and Reduces -Amyloid-Induced Toxicity Due to Activation of Protein Kinase C (PKC) and ERK.Med Sci Monit. 2018 Dec 12;24:9007-9018. doi: 10.12659/MSM.912862.
• [42] Nuclear and Mitochondrial DNA Methylation Patterns Induced by Valproic Acid in Human Hepatocytes. Chem Res Toxicol. 2017 Oct 16;30(10):1847-1854. doi: 10.1021/acs.chemrestox.7b00171. Epub 2017 Sep 13.
• [43] Tissue-specific mtDNA lesions and radical-associated mitochondrial dysfunction in human hearts exposed to doxorubicin. J Pathol. 2005 Dec;207(4):436-44. doi: 10.1002/path.1863.
• [44] Identification of estrogen-induced genes downregulated by AhR agonists in MCF-7 breast cancer cells using suppression subtractive hybridization. Gene. 2001 Jan 10;262(1-2):207-14. doi: 10.1016/s0378-1119(00)00530-8.
• [45] 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.
• [46] Aberrant cell proliferation by enhanced mitochondrial biogenesis via mtTFA in arsenical skin cancers. Am J Pathol. 2011 May;178(5):2066-76.
• [47] Quantitative proteomic analysis of HepG2 cells treated with quercetin suggests IQGAP1 involved in quercetin-induced regulation of cell proliferation and migration. OMICS. 2009 Apr;13(2):93-103. doi: 10.1089/omi.2008.0075.
• [48] Tea polyphenols ameliorates neural redox imbalance and mitochondrial dysfunction via mechanisms linking the key circadian regular Bmal1. Food Chem Toxicol. 2017 Dec;110:189-199. doi: 10.1016/j.fct.2017.10.031. Epub 2017 Oct 20.
• [49] Single-cell Transcriptome Mapping Identifies Common and Cell-type Specific Genes Affected by Acute Delta9-tetrahydrocannabinol in Humans. Sci Rep. 2020 Feb 26;10(1):3450. doi: 10.1038/s41598-020-59827-1.
• [50] Pod-based menthol and tobacco flavored e-cigarettes cause mitochondrial dysfunction in lung epithelial cells. Toxicol Lett. 2020 Oct 15;333:303-311. doi: 10.1016/j.toxlet.2020.08.003. Epub 2020 Aug 9.
• [51] Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to Zidovudine. Environ Mol Mutagen. 2007 Apr-May;48(3-4):179-89. doi: 10.1002/em.20245.
• [52] Identification of biomarkers modulated by the rexinoid LGD1069 (bexarotene) in human breast cells using oligonucleotide arrays. Cancer Res. 2006 Dec 15;66(24):12009-18.
• [53] A genome-wide analysis of targets of macrolide antibiotics in mammalian cells. J Biol Chem. 2020 Feb 14;295(7):2057-2067. doi: 10.1074/jbc.RA119.010770. Epub 2020 Jan 8.
• [54] Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human adrenocortical cells. Endocr Relat Cancer. 2013 May 21;20(3):371-81.
• [55] In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells. Antimicrob Agents Chemother. 2006 Nov;50(11):3824-32. doi: 10.1128/AAC.00437-06. Epub 2006 Aug 28.
• [56] Insights into the mechanisms of telbivudine-induced myopathy associated with mitochondrial dysfunction. Chem Biol Interact. 2023 Sep 25;383:110692. doi: 10.1016/j.cbi.2023.110692. Epub 2023 Sep 1.
• [57] Beneficial effects of resveratrol on respiratory chain defects in patients' fibroblasts involve estrogen receptor and estrogen-related receptor alpha signaling. Hum Mol Genet. 2014 Apr 15;23(8):2106-19.
• [58] Mechanisms of Chronic Fialuridine Hepatotoxicity as Revealed in Primary Human Hepatocyte Spheroids. Toxicol Sci. 2019 Oct 1;171(2):385-395. doi: 10.1093/toxsci/kfz195.
• [59] Effects of BMS-986094, a Guanosine Nucleotide Analogue, on Mitochondrial DNA Synthesis and Function. Toxicol Sci. 2016 Oct;153(2):396-408. doi: 10.1093/toxsci/kfw135. Epub 2016 Jul 27.
• [60] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [61] Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
• [62] Melatonin ameliorates acute lung injury caused by paraquat poisoning by promoting PINK1 and BNIP3 expression. Toxicology. 2023 May 15;490:153506. doi: 10.1016/j.tox.2023.153506. Epub 2023 Apr 5.
• [63] Oxaloacetate enhances neuronal cell bioenergetic fluxes and infrastructure. J Neurochem. 2016 Apr;137(1):76-87. doi: 10.1111/jnc.13545. Epub 2016 Mar 11.
• [64] Alterations in metabolism-related genes induced in SHSY5Y cells by okadaic acid exposure. J Toxicol Environ Health A. 2012;75(13-15):844-56. doi: 10.1080/15287394.2012.690703.
• [65] The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts. Toxicol Appl Pharmacol. 2012 May 15;261(1):42-9. doi: 10.1016/j.taap.2012.03.009.