Details of Drug Off-Target (DOT)

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

• DOT Name: Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1)
• Synonyms: HsMAD2; Mitotic arrest deficient 2-like protein 1; MAD2-like protein 1
• Gene Name: MAD2L1
• Related Disease:
  Adenocarcinoma
  B-cell lymphoma
  B-cell neoplasm
  Bladder cancer
  Bone osteosarcoma
  Breast neoplasm
  Chromosomal disorder
  Clear cell renal carcinoma
  Colon carcinoma
  Colorectal carcinoma
  Colorectal neoplasm
  Epithelial ovarian cancer
  Glioma
  Hepatocellular carcinoma
  Lung adenocarcinoma
  Lung neoplasm
  Myelodysplastic syndrome
  Nasopharyngeal carcinoma
  Neoplasm
  Non-small-cell lung cancer
  Oral cancer
  Osteoarthritis
  Osteosarcoma
  Polycystic ovarian syndrome
  Retinoblastoma
  Small-cell lung cancer
  Thrombocytopenia
  Transitional cell carcinoma
  Ulcerative colitis
  Urinary bladder cancer
  Urinary bladder neoplasm
  Carcinoma
  Gastric neoplasm
  Lung cancer
  Lung carcinoma
  Malignant soft tissue neoplasm
  Sarcoma
  Squamous cell carcinoma
  Stomach cancer
  Adult lymphoma
  Esophageal squamous cell carcinoma
  Gastric cancer
  Lymphoma
  Neuroblastoma
  Pediatric lymphoma
  Small lymphocytic lymphoma
  Thyroid tumor
• UniProt ID: MD2L1_HUMAN
• PDB ID: 1DUJ; 1GO4; 1KLQ; 1S2H; 2QYF; 2V64; 2VFX; 3GMH; 5KHU; 5LCW; 6F0X; 6TLJ
• Pfam ID: PF02301
• Sequence:
  MALQLSREQGITLRGSAEIVAEFFSFGINSILYQRGIYPSETFTRVQKYGLTLLVTTDLE
  LIKYLNNVVEQLKDWLYKCSVQKLVVVISNIESGEVLERWQFDIECDKTAKDDSAPREKS
  QKAIQDEIRSVIRQITATVTFLPLLEVSCSFDLLIYTDKDLVVPEKWEESGPQFITNSEE
  VRLRSFTTTIHKVNSMVAYKIPVND
• Function: Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. In the closed conformation (C-MAD2) forms a heterotetrameric complex with MAD1L1 at unattached kinetochores during prometaphase, the complex recruits open conformation molecules of MAD2L1 (O-MAD2) and then promotes the conversion of O-MAD2 to C-MAD2. Required for the execution of the mitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
  Progesterone-mediated oocyte maturation (hsa04914)
  Human T-cell leukemia virus 1 infection (hsa05166)
• Reactome Pathway:
  Inactivation of APC/C via direct inhibition of the APC/C complex (R-HSA-141430)
  Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal (R-HSA-141444)
  Cdc20 (R-HSA-174184)
  APC/C (R-HSA-176409)
  APC-Cdc20 mediated degradation of Nek2A (R-HSA-179409)
  Separation of Sister Chromatids (R-HSA-2467813)
  Resolution of Sister Chromatid Cohesion (R-HSA-2500257)
  RHO GTPases Activate Formins (R-HSA-5663220)
  Mitotic Prometaphase (R-HSA-68877)
  EML4 and NUDC in mitotic spindle formation (R-HSA-9648025)
  Inhibition of the proteolytic activity of APC/C required for the onset of anaphase by mitotic spindle checkpoint components (R-HSA-141405)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[1]
B-cell lymphoma	DISIH1YQ	Strong	Altered Expression	[2]
B-cell neoplasm	DISVY326	Strong	Biomarker	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Bone osteosarcoma	DIST1004	Strong	Biomarker	[5]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[6]
Chromosomal disorder	DISM5BB5	Strong	Genetic Variation	[7]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[8]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[9]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[10]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[11]
Epithelial ovarian cancer	DIS56MH2	Strong	Altered Expression	[12]
Glioma	DIS5RPEH	Strong	Biomarker	[13]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	Strong	Biomarker	[15]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[16]
Myelodysplastic syndrome	DISYHNUI	Strong	Biomarker	[17]
Nasopharyngeal carcinoma	DISAOTQ0	Strong	Biomarker	[18]
Neoplasm	DISZKGEW	Strong	Altered Expression	[19]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[20]
Oral cancer	DISLD42D	Strong	Altered Expression	[21]
Osteoarthritis	DIS05URM	Strong	Altered Expression	[22]
Osteosarcoma	DISLQ7E2	Strong	Biomarker	[5]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[23]
Retinoblastoma	DISVPNPB	Strong	Altered Expression	[24]
Small-cell lung cancer	DISK3LZD	Strong	Biomarker	[25]
Thrombocytopenia	DISU61YW	Strong	Altered Expression	[17]
Transitional cell carcinoma	DISWVVDR	Strong	Altered Expression	[26]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[27]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Carcinoma	DISH9F1N	moderate	Biomarker	[26]
Gastric neoplasm	DISOKN4Y	moderate	Biomarker	[28]
Lung cancer	DISCM4YA	moderate	Altered Expression	[24]
Lung carcinoma	DISTR26C	moderate	Altered Expression	[24]
Malignant soft tissue neoplasm	DISTC6NO	moderate	Altered Expression	[29]
Sarcoma	DISZDG3U	moderate	Altered Expression	[29]
Squamous cell carcinoma	DISQVIFL	moderate	Biomarker	[30]
Stomach cancer	DISKIJSX	moderate	Altered Expression	[31]
Adult lymphoma	DISK8IZR	Limited	Biomarker	[32]
Esophageal squamous cell carcinoma	DIS5N2GV	Limited	Altered Expression	[33]
Gastric cancer	DISXGOUK	Limited	Altered Expression	[31]
Lymphoma	DISN6V4S	Limited	Biomarker	[32]
Neuroblastoma	DISVZBI4	Limited	Altered Expression	[34]
Pediatric lymphoma	DIS51BK2	Limited	Biomarker	[32]
Small lymphocytic lymphoma	DIS30POX	Limited	Biomarker	[32]
Thyroid tumor	DISLVKMD	Limited	Altered Expression	[35]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Paclitaxel	DMLB81S	Approved	Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) affects the response to substance of Paclitaxel.	[33]
Vinblastine	DM5TVS3	Approved	Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) affects the response to substance of Vinblastine.	[73]
Docetaxel	DMDI269	Approved	Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1) affects the response to substance of Docetaxel.	[33]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[36]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[37]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[38]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[39]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[40]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[41]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[42]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[43]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[45]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[46]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[47]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[48]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[47]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[49]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[50]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[51]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[52]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[53]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[54]
Irinotecan	DMP6SC2	Approved	Irinotecan decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[55]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[56]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[57]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[58]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[59]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[60]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[61]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[62]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[63]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[64]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[65]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[66]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[67]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[68]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[69]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[42]
geraniol	DMS3CBD	Investigative	geraniol decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[70]
SC-560	DMT1GJL	Investigative	SC-560 decreases the expression of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[71]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Mitotic spindle assembly checkpoint protein MAD2A (MAD2L1).	[44]

References

• [1] Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients.Lung Cancer. 2011 Oct;74(1):124-31. doi: 10.1016/j.lungcan.2011.01.025. Epub 2011 Mar 4.
• [2] Mad2 overexpression is associated with high cell proliferation and reduced disease-free survival in primary gastrointestinal diffuse large B-cell lymphoma.Hematology. 2016 Aug;21(7):399-403. doi: 10.1080/10245332.2015.1101970. Epub 2016 Mar 16.
• [3] Methylation of p16INK4A and mitotic arrest defective protein 2 (MAD2) genes in gastric marginal-zone B-cell lymphomas.Acta Haematol. 2008;120(4):217-24. doi: 10.1159/000195698. Epub 2009 Jan 28.
• [4] Elevated TRIP13 drives cell proliferation and drug resistance in bladder cancer.Am J Transl Res. 2019 Jul 15;11(7):4397-4410. eCollection 2019.
• [5] Gene expression profiling analysis of osteosarcoma cell lines.Mol Med Rep. 2015 Sep;12(3):4266-4272. doi: 10.3892/mmr.2015.3958. Epub 2015 Jun 18.
• [6] Expression and mutational analyses of the human MAD2L1 gene in breast cancer cells.Genes Chromosomes Cancer. 2000 Dec;29(4):356-62. doi: 10.1002/1098-2264(2000)9999:9999<::aid-gcc1044>3.0.co;2-n.
• [7] Genetic variation in the major mitotic checkpoint genes associated with chromosomal aberrations in healthy humans.Cancer Lett. 2016 Oct 1;380(2):442-446. doi: 10.1016/j.canlet.2016.07.011. Epub 2016 Jul 15.
• [8] miR-28-5p promotes chromosomal instability in VHL-associated cancers by inhibiting Mad2 translation.Cancer Res. 2014 May 1;74(9):2432-43. doi: 10.1158/0008-5472.CAN-13-2041. Epub 2014 Feb 3.
• [9] Therapeutic targeting of the mitotic spindle checkpoint through nanoparticle-mediated siRNA delivery inhibits tumor growth in vivo.Cancer Lett. 2011 May 28;304(2):128-36. doi: 10.1016/j.canlet.2011.02.014. Epub 2011 Mar 5.
• [10] MAD1L1 Arg558His and MAD2L1 Leu84Met interaction with smoking increase the risk of colorectal cancer.Sci Rep. 2015 Jul 17;5:12202. doi: 10.1038/srep12202.
• [11] Aneuploidy is associated with TP53 expression but not with BRCA1 or TERT expression in sporadic colorectal cancer.Anticancer Res. 2009 Nov;29(11):4381-7.
• [12] BRCA1 and MAD2 Are Coexpressed and Are Prognostic Indicators in Tubo-ovarian High-Grade Serous Carcinoma.Int J Gynecol Cancer. 2018 Mar;28(3):472-478. doi: 10.1097/IGC.0000000000001214.
• [13] MAD2-p31(comet) axis deficiency reduces cell proliferation, migration and sensitivity of microtubule-interfering agents in glioma.Biochem Biophys Res Commun. 2018 Mar 25;498(1):157-163. doi: 10.1016/j.bbrc.2018.02.011. Epub 2018 Feb 3.
• [14] Aberrant expression of cell cycle and material metabolism related genes contributes to hepatocellular carcinoma occurrence.Pathol Res Pract. 2017 Apr;213(4):316-321. doi: 10.1016/j.prp.2017.01.019. Epub 2017 Jan 25.
• [15] Prognostic and predictive values of CDK1 and MAD2L1 in lung adenocarcinoma.Oncotarget. 2016 Dec 20;7(51):85235-85243. doi: 10.18632/oncotarget.13252.
• [16] Upregulation of Mad2 facilitates invivo and invitro osteosarcoma progression.Oncol Rep. 2012 Dec;28(6):2170-6. doi: 10.3892/or.2012.2032. Epub 2012 Sep 17.
• [17] Prognostic importance of Aurora Kinases and mitotic spindle genes transcript levels in Myelodysplastic syndrome.Leuk Res. 2018 Jan;64:61-70. doi: 10.1016/j.leukres.2017.11.013. Epub 2017 Nov 28.
• [18] Mitotic arrest deficient 2 expression induces chemosensitization to a DNA-damaging agent, cisplatin, in nasopharyngeal carcinoma cells.Cancer Res. 2005 Feb 15;65(4):1450-8. doi: 10.1158/0008-5472.CAN-04-0567.
• [19] MiR-200c-5p suppresses proliferation and metastasis of human hepatocellular carcinoma (HCC) via suppressing MAD2L1.Biomed Pharmacother. 2017 Aug;92:1038-1044. doi: 10.1016/j.biopha.2017.05.092. Epub 2017 Jun 10.
• [20] Identification and Integrated Analysis of Key Biomarkers for Diagnosis and Prognosis of Non-Small Cell Lung Cancer.Med Sci Monit. 2019 Dec 5;25:9280-9289. doi: 10.12659/MSM.918620.
• [21] Clinicopathologic significance of BubR1 and Mad2 overexpression in oral cancer.Oral Dis. 2015 Sep;21(6):713-20. doi: 10.1111/odi.12335. Epub 2015 Apr 6.
• [22] Genome-wide expression and methylation profiles reveal candidate genes and biological processes underlying synovial inflammatory tissue of patients with osteoarthritis.Int J Rheum Dis. 2015 Sep;18(7):783-90. doi: 10.1111/1756-185X.12643. Epub 2015 Jul 14.
• [23] Progesterone resistance in PCOS endometrium: a microarray analysis in clomiphene citrate-treated and artificial menstrual cycles.J Clin Endocrinol Metab. 2011 Jun;96(6):1737-46. doi: 10.1210/jc.2010-2600. Epub 2011 Mar 16.
• [24] Inhibition of Skp2 sensitizes lung cancer cells to paclitaxel.Onco Targets Ther. 2017 Jan 18;10:439-446. doi: 10.2147/OTT.S125789. eCollection 2017.
• [25] Identification of candidate genes associated with the pathogenesis of small cell lung cancer via integrated bioinformatics analysis.Oncol Lett. 2019 Oct;18(4):3723-3733. doi: 10.3892/ol.2019.10685. Epub 2019 Jul 29.
• [26] High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer.Virchows Arch. 2013 Nov;463(5):681-7. doi: 10.1007/s00428-013-1473-6. Epub 2013 Aug 31.
• [27] Spindle proteins Aurora A and BUB1B, but not Mad2, are aberrantly expressed in dysplastic mucosa of patients with longstanding ulcerative colitis.J Clin Pathol. 2007 Dec;60(12):1403-8. doi: 10.1136/jcp.2006.044305. Epub 2007 Feb 23.
• [28] Depression of MAD2 inhibits apoptosis of gastric cancer cells by upregulating Bcl-2 and interfering mitochondrion pathway.Biochem Biophys Res Commun. 2006 Jul 7;345(3):1092-8. doi: 10.1016/j.bbrc.2006.04.172. Epub 2006 May 8.
• [29] Aberrant MAD2 expression in soft-tissue sarcoma.Pathol Int. 2008 Jun;58(6):329-33. doi: 10.1111/j.1440-1827.2008.02232.x.
• [30] MAD2 expression in oral squamous cell carcinoma and its relationship to tumor grade and proliferation.Anticancer Res. 2014 Dec;34(12):7021-7.
• [31] Spindle assembly checkpoint MAD2 and CDC20 overexpressions and cell-in-cell formation in gastric cancer and its precursor lesions.Hum Pathol. 2019 Mar;85:174-183. doi: 10.1016/j.humpath.2018.10.029. Epub 2018 Nov 15.
• [32] Mitotic slippage: an old tale with a new twist.Cell Cycle. 2019 Jan;18(1):7-15. doi: 10.1080/15384101.2018.1559557. Epub 2019 Jan 2.
• [33] Mitotic checkpoint genes, hsMAD2 and BubR1, in oesophageal squamous cancer cells and their association with 5-fluorouracil and cisplatin-based radiochemotherapy. Clin Oncol (R Coll Radiol). 2008 Oct;20(8):639-46. doi: 10.1016/j.clon.2008.06.010. Epub 2008 Aug 8.
• [34] HsMAD2 mRNA expression may be a predictor of sensitivity to paclitaxel and survival in neuroblastoma.Pediatr Surg Int. 2011 Feb;27(2):217-23. doi: 10.1007/s00383-010-2780-5.
• [35] Overexpression of the mitotic spindle assembly checkpoint genes hBUB1, hBUBR1 and hMAD2 in thyroid carcinomas with aggressive nature.Anticancer Res. 2008 Jan-Feb;28(1A):139-44.
• [36] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [37] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [38] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [39] Two distinct modes of cell death induced by doxorubicin: apoptosis and cell death through mitotic catastrophe accompanied by senescence-like phenotype. Oncogene. 2005 Jul 14;24(30):4765-77.
• [40] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [41] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [42] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [43] 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.
• [44] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [45] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [46] Gene expression profile induced by arsenic trioxide in chronic lymphocytic leukemia cells reveals a central role for heme oxygenase-1 in apoptosis and regulation of matrix metalloproteinase-9. Oncotarget. 2016 Dec 13;7(50):83359-83377.
• [47] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [48] 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.
• [49] Gene expression profiling of breast cancer cells in response to gemcitabine: NF-kappaB pathway activation as a potential mechanism of resistance. Breast Cancer Res Treat. 2007 Apr;102(2):157-72.
• [50] mTOR inhibition reverses acquired endocrine therapy resistance of breast cancer cells at the cell proliferation and gene-expression levels. Cancer Sci. 2008 Oct;99(10):1992-2003. doi: 10.1111/j.1349-7006.2008.00955.x.
• [51] Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells initro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology. 2017 Jun;152(8):2022-2036.
• [52] Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
• [53] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [54] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [55] In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
• [56] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [57] Dasatinib reverses cancer-associated fibroblasts (CAFs) from primary lung carcinomas to a phenotype comparable to that of normal fibroblasts. Mol Cancer. 2010 Jun 27;9:168.
• [58] Simvastatin inactivates beta1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells. Cancer Sci. 2007 Jun;98(6):890-9.
• [59] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [60] Microarray analysis of bicalutamide action on telomerase activity, p53 pathway and viability of prostate carcinoma cell lines. J Pharm Pharmacol. 2005 Jan;57(1):83-92.
• [61] Resveratrol-induced gene expression profiles in human prostate cancer cells. Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):596-604. doi: 10.1158/1055-9965.EPI-04-0398.
• [62] Camptothecin induces mitotic arrest through Mad2-Cdc20 complex by activating the JNK-mediated Sp1 pathway. Food Chem Toxicol. 2019 May;127:143-155. doi: 10.1016/j.fct.2019.03.026. Epub 2019 Mar 15.
• [63] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [64] Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis. Environ Mol Mutagen. 2009 Jan;50(1):46-59.
• [65] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [66] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
• [67] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [68] Bisphenol-A exposure and gene expression in human luteinized membrana granulosa cells in vitro. Hum Reprod. 2017 Feb;32(2):409-417. doi: 10.1093/humrep/dew316. Epub 2016 Dec 15.
• [69] MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells. Toxicol Lett. 2013 Jul 31;221(1):23-30. doi: 10.1016/j.toxlet.2013.05.643. Epub 2013 Jun 13.
• [70] Geraniol suppresses prostate cancer growth through down-regulation of E2F8. Cancer Med. 2016 Oct;5(10):2899-2908.
• [71] Gene modulation by Cox-1 and Cox-2 specific inhibitors in human colorectal carcinoma cancer cells. Carcinogenesis. 2004 Mar;25(3):349-57.
• [72] Mitotic checkpoint genes, hsMAD2 and BubR1, in oesophageal squamous cancer cells and their association with 5-fluorouracil and cisplatin-based radiochemotherapy. Clin Oncol (R Coll Radiol). 2008 Oct;20(8):639-46. doi: 10.1016/j.clon.2008.06.010. Epub 2008 Aug 8.
• [73] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.