Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX93FE7)

• DOT Name: Cell division control protein 6 homolog (CDC6)
• Synonyms: CDC6-related protein; Cdc18-related protein; HsCdc18; p62(cdc6); HsCDC6
• Gene Name: CDC6
• Related Disease:
  Bone osteosarcoma
  Cervical cancer
  Cervical carcinoma
  Gastric cancer
  Meier-Gorlin syndrome 5
  Myeloproliferative neoplasm
  Osteosarcoma
  Seckel syndrome
  Stomach cancer
  Benign prostatic hyperplasia
  Breast neoplasm
  Endometriosis
  Epithelial ovarian cancer
  Hepatitis B virus infection
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Lymphoma, non-Hodgkin, familial
  Mantle cell lymphoma
  Matthew-Wood syndrome
  Mungan syndrome
  Non-hodgkin lymphoma
  Ovarian cancer
  Ovarian neoplasm
  Polycystic ovarian syndrome
  Prostate neoplasm
  Psoriasis
  Squamous cell carcinoma
  Bladder cancer
  Carcinoma
  Chronic obstructive pulmonary disease
  Colorectal carcinoma
  Neoplasm
  Neuroblastoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Meier-Gorlin syndrome
  Adenocarcinoma
  Advanced cancer
  Breast cancer
  Breast carcinoma
  Gallbladder carcinoma
  Isolated congenital microcephaly
  Melanoma
  Nasopharyngeal carcinoma
  Prostate cancer
  Prostate carcinoma
• UniProt ID: CDC6_HUMAN
• PDB ID: 2CCH; 2CCI; 4I5L; 4I5N
• Pfam ID: PF13401 ; PF17872 ; PF09079
• Sequence:
  MPQTRSQAQATISFPKRKLSRALNKAKNSSDAKLEPTNVQTVTCSPRVKALPLSPRKRLG
  DDNLCNTPHLPPCSPPKQGKKENGPPHSHTLKGRRLVFDNQLTIKSPSKRELAKVHQNKI
  LSSVRKSQEITTNSEQRCPLKKESACVRLFKQEGTCYQQAKLVLNTAVPDRLPAREREMD
  VIRNFLREHICGKKAGSLYLSGAPGTGKTACLSRILQDLKKELKGFKTIMLNCMSLRTAQ
  AVFPAIAQEICQEEVSRPAGKDMMRKLEKHMTAEKGPMIVLVLDEMDQLDSKGQDVLYTL
  FEWPWLSNSHLVLIGIANTLDLTDRILPRLQAREKCKPQLLNFPPYTRNQIVTILQDRLN
  QVSRDQVLDNAAVQFCARKVSAVSGDVRKALDVCRRAIEIVESDVKSQTILKPLSECKSP
  SEPLIPKRVGLIHISQVISEVDGNRMTLSQEGAQDSFPLQQKILVCSLMLLIRQLKIKEV
  TLGKLYEAYSKVCRKQQVAAVDQSECLSLSGLLEARGILGLKRNKETRLTKVFFKIEEKE
  IEHALKDKALIGNILATGLP
• Function: Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Chemical carcinogenesis - receptor activation (hsa05207)
• Reactome Pathway:
  Activation of ATR in response to replication stress (R-HSA-176187)
  CDC6 association with the ORC (R-HSA-68689)
  Assembly of the pre-replicative complex (R-HSA-68867)
  Orc1 removal from chromatin (R-HSA-68949)
  Activation of the pre-replicative complex (R-HSA-68962)
  CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017)
  G1/S-Specific Transcription (R-HSA-69205)
  Transcription of E2F targets under negative control by DREAM complex (R-HSA-1362277)

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Altered Expression	[1]
Cervical cancer	DISFSHPF	Definitive	Genetic Variation	[2]
Cervical carcinoma	DIST4S00	Definitive	Genetic Variation	[2]
Gastric cancer	DISXGOUK	Definitive	Biomarker	[3]
Meier-Gorlin syndrome 5	DISXGFBC	Definitive	Autosomal recessive	[4]
Myeloproliferative neoplasm	DIS5KAPA	Definitive	Biomarker	[5]
Osteosarcoma	DISLQ7E2	Definitive	Altered Expression	[1]
Seckel syndrome	DISEVUBA	Definitive	Biomarker	[5]
Stomach cancer	DISKIJSX	Definitive	Biomarker	[3]
Benign prostatic hyperplasia	DISI3CW2	Strong	Altered Expression	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Endometriosis	DISX1AG8	Strong	Biomarker	[8]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[9]
Hepatitis B virus infection	DISLQ2XY	Strong	Altered Expression	[10]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[11]
Lung cancer	DISCM4YA	Strong	Biomarker	[12]
Lung carcinoma	DISTR26C	Strong	Biomarker	[12]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Genetic Variation	[13]
Mantle cell lymphoma	DISFREOV	Strong	Altered Expression	[14]
Matthew-Wood syndrome	DISA7HR7	Strong	Altered Expression	[15]
Mungan syndrome	DISNR0AY	Strong	Genetic Variation	[16]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[13]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[9]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[9]
Polycystic ovarian syndrome	DISZ2BNG	Strong	Biomarker	[17]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[18]
Psoriasis	DIS59VMN	Strong	Altered Expression	[19]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[20]
Bladder cancer	DISUHNM0	moderate	Biomarker	[21]
Carcinoma	DISH9F1N	moderate	Altered Expression	[20]
Chronic obstructive pulmonary disease	DISQCIRF	moderate	Biomarker	[22]
Colorectal carcinoma	DIS5PYL0	moderate	Biomarker	[23]
Neoplasm	DISZKGEW	moderate	Biomarker	[3]
Neuroblastoma	DISVZBI4	moderate	Altered Expression	[24]
Urinary bladder cancer	DISDV4T7	moderate	Biomarker	[21]
Urinary bladder neoplasm	DIS7HACE	moderate	Biomarker	[21]
Meier-Gorlin syndrome	DISCFIU3	Supportive	Autosomal dominant	[25]
Adenocarcinoma	DIS3IHTY	Limited	Altered Expression	[26]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[27]
Breast cancer	DIS7DPX1	Limited	Biomarker	[28]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[28]
Gallbladder carcinoma	DISD6ACL	Limited	Altered Expression	[26]
Isolated congenital microcephaly	DISUXHZ6	Limited	Biomarker	[16]
Melanoma	DIS1RRCY	Limited	Biomarker	[29]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Biomarker	[30]
Prostate cancer	DISF190Y	Limited	Altered Expression	[6]
Prostate carcinoma	DISMJPLE	Limited	Altered Expression	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cell division control protein 6 homolog (CDC6).	[31]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cell division control protein 6 homolog (CDC6).	[32]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cell division control protein 6 homolog (CDC6).	[33]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cell division control protein 6 homolog (CDC6).	[34]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Cell division control protein 6 homolog (CDC6).	[35]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Cell division control protein 6 homolog (CDC6).	[36]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Cell division control protein 6 homolog (CDC6).	[37]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cell division control protein 6 homolog (CDC6).	[38]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Cell division control protein 6 homolog (CDC6).	[39]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Cell division control protein 6 homolog (CDC6).	[40]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cell division control protein 6 homolog (CDC6).	[40]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Cell division control protein 6 homolog (CDC6).	[41]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cell division control protein 6 homolog (CDC6).	[42]
Progesterone	DMUY35B	Approved	Progesterone increases the expression of Cell division control protein 6 homolog (CDC6).	[43]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of Cell division control protein 6 homolog (CDC6).	[44]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of Cell division control protein 6 homolog (CDC6).	[45]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Cell division control protein 6 homolog (CDC6).	[46]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of Cell division control protein 6 homolog (CDC6).	[47]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of Cell division control protein 6 homolog (CDC6).	[48]
Azathioprine	DMMZSXQ	Approved	Azathioprine decreases the expression of Cell division control protein 6 homolog (CDC6).	[49]
Etoposide	DMNH3PG	Approved	Etoposide decreases the expression of Cell division control protein 6 homolog (CDC6).	[50]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Cell division control protein 6 homolog (CDC6).	[42]
Piroxicam	DMTK234	Approved	Piroxicam increases the expression of Cell division control protein 6 homolog (CDC6).	[51]
Dasatinib	DMJV2EK	Approved	Dasatinib decreases the expression of Cell division control protein 6 homolog (CDC6).	[52]
Mitomycin	DMH0ZJE	Approved	Mitomycin decreases the expression of Cell division control protein 6 homolog (CDC6).	[36]
Simvastatin	DM30SGU	Approved	Simvastatin decreases the expression of Cell division control protein 6 homolog (CDC6).	[53]
Lucanthone	DMZLBUO	Approved	Lucanthone decreases the expression of Cell division control protein 6 homolog (CDC6).	[54]
Bicalutamide	DMZMSPF	Approved	Bicalutamide decreases the expression of Cell division control protein 6 homolog (CDC6).	[18]
Colchicine	DM2POTE	Approved	Colchicine decreases the expression of Cell division control protein 6 homolog (CDC6).	[36]
Adenine	DMZLHKJ	Approved	Adenine decreases the expression of Cell division control protein 6 homolog (CDC6).	[36]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of Cell division control protein 6 homolog (CDC6).	[56]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene decreases the expression of Cell division control protein 6 homolog (CDC6).	[33]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of Cell division control protein 6 homolog (CDC6).	[57]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Cell division control protein 6 homolog (CDC6).	[37]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of Cell division control protein 6 homolog (CDC6).	[58]
Plevitrexed	DM7Y60I	Phase 2	Plevitrexed increases the expression of Cell division control protein 6 homolog (CDC6).	[59]
PX-866	DMYISJK	Phase 2	PX-866 decreases the expression of Cell division control protein 6 homolog (CDC6).	[60]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Cell division control protein 6 homolog (CDC6).	[62]
TDZD-8	DMG6Q45	Patented	TDZD-8 decreases the expression of Cell division control protein 6 homolog (CDC6).	[64]
Scriptaid	DM9JZ21	Preclinical	Scriptaid affects the expression of Cell division control protein 6 homolog (CDC6).	[65]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cell division control protein 6 homolog (CDC6).	[66]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Cell division control protein 6 homolog (CDC6).	[67]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Cell division control protein 6 homolog (CDC6).	[68]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of Cell division control protein 6 homolog (CDC6).	[69]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of Cell division control protein 6 homolog (CDC6).	[70]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of Cell division control protein 6 homolog (CDC6).	[71]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Cell division control protein 6 homolog (CDC6).	[72]
Lithium chloride	DMHYLQ2	Investigative	Lithium chloride decreases the expression of Cell division control protein 6 homolog (CDC6).	[64]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE decreases the expression of Cell division control protein 6 homolog (CDC6).	[73]
Forskolin	DM6ITNG	Investigative	Forskolin increases the expression of Cell division control protein 6 homolog (CDC6).	[74]

2 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 Cell division control protein 6 homolog (CDC6).	[61]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Cell division control protein 6 homolog (CDC6).	[63]

References

• [1] Downregulation of Cdc6 inhibits tumorigenesis of osteosarcoma in vivo and in vitro.Biomed Pharmacother. 2019 Jul;115:108949. doi: 10.1016/j.biopha.2019.108949. Epub 2019 May 14.
• [2] Association between the CDC6 G1321A polymorphism and the risk of cervical cancer.Int J Gynecol Cancer. 2010 Jul;20(5):856-61. doi: 10.1111/IGC.0b013e3181df3cab.
• [3] MicroRNA-1297 inhibits proliferation and promotes apoptosis in gastric cancer cells by downregulating CDC6 expression.Anticancer Drugs. 2019 Sep;30(8):803-811. doi: 10.1097/CAD.0000000000000776.
• [4] Meier-Gorlin syndrome: report of eight additional cases and review. Am J Med Genet. 2001 Aug 1;102(2):115-24. doi: 10.1002/ajmg.1452.
• [5] Meier-Gorlin syndrome genotype-phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis.Eur J Hum Genet. 2012 Jun;20(6):598-606. doi: 10.1038/ejhg.2011.269. Epub 2012 Feb 15.
• [6] CDC6 mRNA Expression Is Associated with the Aggressiveness of Prostate Cancer.J Korean Med Sci. 2018 Nov 2;33(47):e303. doi: 10.3346/jkms.2018.33.e303. eCollection 2018 Nov 19.
• [7] Vaccinia virus GLV-1h237 carrying a Walker A motif mutation of mouse Cdc6 protein enhances human breast tumor therapy in mouse xenografts.Int J Oncol. 2011 Mar;38(3):871-8. doi: 10.3892/ijo.2011.910. Epub 2011 Jan 18.
• [8] The peritoneum is both a source and target of TGF- in women with endometriosis.PLoS One. 2014 Sep 10;9(9):e106773. doi: 10.1371/journal.pone.0106773. eCollection 2014.
• [9] Prediction of key genes in ovarian cancer treated with decitabine based on network strategy.Oncol Rep. 2016 Jun;35(6):3548-58. doi: 10.3892/or.2016.4697. Epub 2016 Mar 23.
• [10] HBx protein of hepatitis B virus promotes reinitiation of DNA replication by regulating expression and intracellular stability of replication licensing factor CDC6.J Biol Chem. 2012 Jun 8;287(24):20545-54. doi: 10.1074/jbc.M112.359760. Epub 2012 Apr 19.
• [11] Potential clinical value and putative biological function of miR-122-5p in hepatocellular carcinoma: A comprehensive study using microarray and RNA sequencing data.Oncol Lett. 2018 Dec;16(6):6918-6929. doi: 10.3892/ol.2018.9523. Epub 2018 Sep 28.
• [12] AAV-Mediated angiotensin 1-7 overexpression inhibits tumor growth of lung cancer in vitro and in vivo.Oncotarget. 2017 Jan 3;8(1):354-363. doi: 10.18632/oncotarget.13396.
• [13] Association analysis between the Cdc6 G1321A polymorphism and the risk for non-Hodgkin lymphoma and hepatocellular carcinoma.Mutat Res. 2009 Mar 9;662(1-2):10-5. doi: 10.1016/j.mrfmmm.2008.11.014. Epub 2008 Dec 3.
• [14] Unbalanced expression of licensing DNA replication factors occurs in a subset of mantle cell lymphomas with genomic instability.Int J Cancer. 2006 Dec 15;119(12):2768-74. doi: 10.1002/ijc.22146.
• [15] eIF4A inhibition circumvents uncontrolled DNA replication mediated by 4E-BP1 loss in pancreatic cancer.JCI Insight. 2019 Nov 1;4(21):e121951. doi: 10.1172/jci.insight.121951.
• [16] Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype.Hum Mol Genet. 2017 Nov 1;26(21):4168-4180. doi: 10.1093/hmg/ddx305.
• [17] 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.
• [18] Androgen receptor regulates Cdc6 in synchronized LNCaP cells progressing from G1 to S phase. J Cell Physiol. 2005 Aug;204(2):381-7. doi: 10.1002/jcp.20422.
• [19] Berberine downregulates CDC6 and inhibits proliferation via targeting JAK-STAT3 signaling in keratinocytes.Cell Death Dis. 2019 Mar 20;10(4):274. doi: 10.1038/s41419-019-1510-8.
• [20] Expression of Mcm7 and Cdc6 in oral squamous cell carcinoma and precancerous lesions.Anticancer Res. 2008 Nov-Dec;28(6A):3763-9.
• [21] Norcantharidin inhibits the DDR of bladder cancer stem-like cells through cdc6 degradation.Onco Targets Ther. 2019 Jun 7;12:4403-4413. doi: 10.2147/OTT.S209907. eCollection 2019.
• [22] A novel polymorphism in CDC6 is associated with the decline in lung function of ex-smokers in COPD.Biochem Biophys Res Commun. 2009 Apr 17;381(4):554-9. doi: 10.1016/j.bbrc.2009.02.080. Epub 2009 Feb 20.
• [23] Screening key genes and signaling pathways in colorectal cancer by integrated bioinformatics analysis.Mol Med Rep. 2019 Aug;20(2):1259-1269. doi: 10.3892/mmr.2019.10336. Epub 2019 Jun 4.
• [24] Cdc6 knockdown inhibits human neuroblastoma cell proliferation.Mol Cell Biochem. 2008 Apr;311(1-2):189-97. doi: 10.1007/s11010-008-9709-5. Epub 2008 Feb 8.
• [25] Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of Meier-Gorlin syndrome. PLoS Genet. 2013;9(3):e1003360. doi: 10.1371/journal.pgen.1003360. Epub 2013 Mar 14.
• [26] Expression of CDC6 and GDF-9 and their clinicopathological significances in benign and malignant lesions of the gallbladder.Cancer Biomark. 2012;11(2-3):107-14. doi: 10.3233/CBM-2012-0267.
• [27] Radiation-promoted CDC6 protein stability contributes to radioresistance by regulating senescence and epithelial to mesenchymal transition.Oncogene. 2019 Jan;38(4):549-563. doi: 10.1038/s41388-018-0460-4. Epub 2018 Aug 29.
• [28] The prognostic significance of Cdc6 and Cdt1 in breast cancer.Sci Rep. 2017 Apr 20;7(1):985. doi: 10.1038/s41598-017-00998-9.
• [29] The protein phosphatase 2A regulatory subunit PR70 is a gonosomal melanoma tumor suppressor gene.Sci Transl Med. 2016 Dec 14;8(369):369ra177. doi: 10.1126/scitranslmed.aai9188.
• [30] Identification of miRNA/mRNA-Negative Regulation Pairs in Nasopharyngeal Carcinoma.Med Sci Monit. 2016 Jun 28;22:2215-34. doi: 10.12659/msm.896047.
• [31] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [32] 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.
• [33] Differential modulation of PI3-kinase/Akt pathway during all-trans retinoic acid- and Am80-induced HL-60 cell differentiation revealed by DNA microarray analysis. Biochem Pharmacol. 2004 Dec 1;68(11):2177-86.
• [34] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [35] RNA sequence analysis of inducible pluripotent stem cell-derived cardiomyocytes reveals altered expression of DNA damage and cell cycle genes in response to doxorubicin. Toxicol Appl Pharmacol. 2018 Oct 1;356:44-53.
• [36] Utilization of CDKN1A/p21 gene for class discrimination of DNA damage-induced clastogenicity. Toxicology. 2014 Jan 6;315:8-16. doi: 10.1016/j.tox.2013.10.009. Epub 2013 Nov 6.
• [37] Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells. Carcinogenesis. 2006 Aug;27(8):1567-78.
• [38] 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.
• [39] Activation of the p38 MAPK/Akt/ERK1/2 signal pathways is required for the protein stabilization of CDC6 and cyclin D1 in low-dose arsenite-induced cell proliferation. J Cell Biochem. 2010 Dec 15;111(6):1546-55. doi: 10.1002/jcb.22886.
• [40] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [41] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [42] Drug-induced endoplasmic reticulum and oxidative stress responses independently sensitize toward TNF-mediated hepatotoxicity. Toxicol Sci. 2014 Jul;140(1):144-59. doi: 10.1093/toxsci/kfu072. Epub 2014 Apr 20.
• [43] Coordinate up-regulation of TMEM97 and cholesterol biosynthesis genes in normal ovarian surface epithelial cells treated with progesterone: implications for pathogenesis of ovarian cancer. BMC Cancer. 2007 Dec 11;7:223.
• [44] 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.
• [45] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [46] 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.
• [47] 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.
• [48] Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
• [49] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [50] Responses of genes involved in cell cycle control to diverse DNA damaging chemicals in human lung adenocarcinoma A549 cells. Cancer Cell Int. 2005 Aug 24;5:28. doi: 10.1186/1475-2867-5-28.
• [51] Apoptosis induced by piroxicam plus cisplatin combined treatment is triggered by p21 in mesothelioma. PLoS One. 2011;6(8):e23569.
• [52] 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.
• [53] 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.
• [54] Lucanthone is a novel inhibitor of autophagy that induces cathepsin D-mediated apoptosis. J Biol Chem. 2011 Feb 25;286(8):6602-13.
• [55] Androgen receptor regulates Cdc6 in synchronized LNCaP cells progressing from G1 to S phase. J Cell Physiol. 2005 Aug;204(2):381-7. doi: 10.1002/jcp.20422.
• [56] 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.
• [57] Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol Endocrinol. 2002 Jun;16(6):1243-56.
• [58] Phenethyl isothiocyanate alters the gene expression and the levels of protein associated with cell cycle regulation in human glioblastoma GBM 8401 cells. Environ Toxicol. 2017 Jan;32(1):176-187.
• [59] P21Cip1 is a critical mediator of the cytotoxic action of thymidylate synthase inhibitors in colorectal carcinoma cells. Cancer Res. 2004 Sep 1;64(17):6296-303. doi: 10.1158/0008-5472.CAN-04-0863.
• [60] Combinatorial PX-866 and Raloxifene Decrease Rb Phosphorylation, Cyclin E2 Transcription, and Proliferation of MCF-7 Breast Cancer Cells. J Cell Biochem. 2016 Jul;117(7):1688-96. doi: 10.1002/jcb.25462. Epub 2015 Dec 28.
• [61] 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.
• [62] 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.
• [63] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [64] Lithium suppresses cell proliferation by interrupting E2F-DNA interaction and subsequently reducing S-phase gene expression in prostate cancer. Prostate. 2007 Jun 15;67(9):976-88. doi: 10.1002/pros.20586.
• [65] Histone deacetylase inhibitor scriptaid induces cell cycle arrest and epigenetic change in colon cancer cells. Int J Oncol. 2008 Oct;33(4):767-76.
• [66] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [67] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [68] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [69] Mapping the cellular response to electron transport chain inhibitors reveals selective signaling networks triggered by mitochondrial perturbation. Arch Toxicol. 2022 Jan;96(1):259-285. doi: 10.1007/s00204-021-03160-7. Epub 2021 Oct 13.
• [70] Molecular signatures of cytotoxic effects in human embryonic kidney 293?cells treated with single and mixture of ochratoxin A and citrinin. Food Chem Toxicol. 2019 Jan;123:374-384. doi: 10.1016/j.fct.2018.11.015. Epub 2018 Nov 11.
• [71] Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines. PLoS One. 2019 Jul 11;14(7):e0219610. doi: 10.1371/journal.pone.0219610. eCollection 2019.
• [72] Genome-wide impact of androgen receptor trapped clone-27 loss on androgen-regulated transcription in prostate cancer cells. Cancer Res. 2009 Apr 1;69(7):3140-7. doi: 10.1158/0008-5472.CAN-08-3738. Epub 2009 Mar 24.
• [73] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [74] Identification of genes targeted by the androgen and PKA signaling pathways in prostate cancer cells. Oncogene. 2006 Nov 23;25(55):7311-23.