Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLD7UID)

• DOT Name: G1/S-specific cyclin-E1 (CCNE1)
• Gene Name: CCNE1
• UniProt ID: CCNE1_HUMAN
• PDB ID: 1W98; 5L2W; 7KJS; 7XQK; 8H4R; 8H6P; 8H6T
• Pfam ID: PF02984 ; PF00134
• Sequence:
  MPRERRERDAKERDTMKEDGGAEFSARSRKRKANVTVFLQDPDEEMAKIDRTARDQCGSQ
  PWDNNAVCADPCSLIPTPDKEDDDRVYPNSTCKPRIIAPSRGSPLPVLSWANREEVWKIM
  LNKEKTYLRDQHFLEQHPLLQPKMRAILLDWLMEVCEVYKLHRETFYLAQDFFDRYMATQ
  ENVVKTLLQLIGISSLFIAAKLEEIYPPKLHQFAYVTDGACSGDEILTMELMIMKALKWR
  LSPLTIVSWLNVYMQVAYLNDLHEVLLPQYPQQIFIQIAELLDLCVLDVDCLEFPYGILA
  ASALYHFSSSELMQKVSGYQWCDIENCVKWMVPFAMVIRETGSSKLKHFRGVADEDAHNI
  QTHRDSLDLLDKARAKKAMLSEQNRASPLPSGLLTPPQSGKKQSSGPEMA
• Function: Essential for the control of the cell cycle at the G1/S (start) transition.
• Tissue Specificity: Highly expressed in testis and placenta. Low levels in bronchial epithelial cells.
• KEGG Pathway:
  Cell cycle (hsa04110)
  Oocyte meiosis (hsa04114)
  p53 sig.ling pathway (hsa04115)
  PI3K-Akt sig.ling pathway (hsa04151)
  Cellular senescence (hsa04218)
  Cushing syndrome (hsa04934)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human papillomavirus infection (hsa05165)
  Human T-cell leukemia virus 1 infection (hsa05166)
  Epstein-Barr virus infection (hsa05169)
  Pathways in cancer (hsa05200)
  Viral carcinogenesis (hsa05203)
  MicroR.s in cancer (hsa05206)
  Prostate cancer (hsa05215)
  Small cell lung cancer (hsa05222)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577)
  DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586)
  Association of TriC/CCT with target proteins during biosynthesis (R-HSA-390471)
  TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest (R-HSA-6804116)
  CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017)
  Phosphorylation of proteins involved in G1/S transition by active Cyclin E (R-HSA-69200)
  Cyclin E associated events during G1/S transition (R-HSA-69202)
  G1/S-Specific Transcription (R-HSA-69205)
  Cyclin D associated events in G1 (R-HSA-69231)
  p53-Dependent G1 DNA Damage Response (R-HSA-69563)
  PTK6 Regulates Cell Cycle (R-HSA-8849470)
  Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (R-HSA-9661069)
  RHOBTB3 ATPase cycle (R-HSA-9706019)
  G0 and Early G1 (R-HSA-1538133)

Molecular Interaction Atlas (MIA) of This DOT

This DOT Affected the Drug Response of 2 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Palbociclib	DMD7L94	Approved	G1/S-specific cyclin-E1 (CCNE1) decreases the response to substance of Palbociclib.	[92]
CYCLOPAMINE	DMEM2SW	Investigative	G1/S-specific cyclin-E1 (CCNE1) increases the response to substance of CYCLOPAMINE.	[93]

3 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 G1/S-specific cyclin-E1 (CCNE1).	[1]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of G1/S-specific cyclin-E1 (CCNE1).	[62]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of G1/S-specific cyclin-E1 (CCNE1).	[66]

95 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 G1/S-specific cyclin-E1 (CCNE1).	[2]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[3]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[6]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[11]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[12]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of G1/S-specific cyclin-E1 (CCNE1).	[13]
Menadione	DMSJDTY	Approved	Menadione affects the expression of G1/S-specific cyclin-E1 (CCNE1).	[14]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[15]
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[16]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of G1/S-specific cyclin-E1 (CCNE1).	[17]
Demecolcine	DMCZQGK	Approved	Demecolcine decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[18]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[19]
Cannabidiol	DM0659E	Approved	Cannabidiol decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[20]
Troglitazone	DM3VFPD	Approved	Troglitazone decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[21]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[22]
Aspirin	DM672AH	Approved	Aspirin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[23]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of G1/S-specific cyclin-E1 (CCNE1).	[13]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[24]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[25]
Topotecan	DMP6G8T	Approved	Topotecan decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[26]
Sulindac	DM2QHZU	Approved	Sulindac decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[27]
Daunorubicin	DMQUSBT	Approved	Daunorubicin affects the expression of G1/S-specific cyclin-E1 (CCNE1).	[28]
Pioglitazone	DMKJ485	Approved	Pioglitazone decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[22]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[29]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[30]
Fluoxetine	DM3PD2C	Approved	Fluoxetine affects the expression of G1/S-specific cyclin-E1 (CCNE1).	[31]
Cholecalciferol	DMGU74E	Approved	Cholecalciferol decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[32]
Orlistat	DMRJSP8	Approved	Orlistat increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[33]
Ciprofloxacin XR	DM2NLS9	Approved	Ciprofloxacin XR decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[34]
Gamolenic acid	DMQN30Z	Approved	Gamolenic acid decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[35]
Teriflunomide	DMQ2FKJ	Approved	Teriflunomide decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[36]
Omacetaxine mepesuccinate	DMPU2WX	Approved	Omacetaxine mepesuccinate increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[37]
Amsacrine	DMZKYIV	Approved	Amsacrine increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[38]
Amlodipine	DMBDAZV	Approved	Amlodipine decreases the activity of G1/S-specific cyclin-E1 (CCNE1).	[39]
Atropine	DMEN6X7	Approved	Atropine increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[40]
Tetracaine	DM9J6C2	Approved	Tetracaine decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[41]
Berberine	DMC5Q8X	Phase 4	Berberine decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[42]
Silymarin	DMXBYQR	Phase 4	Silymarin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[43]
Resveratrol	DM3RWXL	Phase 3	Resveratrol decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[44]
Curcumin	DMQPH29	Phase 3	Curcumin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[45]
Camptothecin	DM6CHNJ	Phase 3	Camptothecin increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[46]
Seocalcitol	DMKL9QO	Phase 3	Seocalcitol decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[32]
HMPL-004	DM29XGY	Phase 3	HMPL-004 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[47]
I3C	DMIGFOR	Phase 3	I3C decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[48]
5-methoxypsoralen	DME2A8X	Phase 3	5-methoxypsoralen decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[49]
Rubitecan	DMDWU1S	Phase 3	Rubitecan decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[50]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[52]
PEITC	DMOMN31	Phase 2	PEITC decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[53]
GDC0941	DM1YAK6	Phase 2	GDC0941 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[54]
Flavopiridol	DMKSUOI	Phase 2	Flavopiridol decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[55]
URSOLIC ACID	DM4SOAW	Phase 2	URSOLIC ACID decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[56]
Netoglitazone	DM8H7OA	Phase 2	Netoglitazone decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[57]
Plevitrexed	DM7Y60I	Phase 2	Plevitrexed increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[58]
Taurocholic acid	DM2LZ8F	Phase 1/2	Taurocholic acid increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[59]
INCB054329	DM7TZL0	Phase 1/2	INCB054329 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[60]
2-hydroxyoleic acid	DMCLKA4	Phase 1/2	2-hydroxyoleic acid increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[61]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[63]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[64]
Ribavirin	DMEYLH9	Phase 1 Trial	Ribavirin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[65]
IRX4204	DM9SCME	Phase 1	IRX4204 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[35]
LY293111	DM03FHA	Discontinued in Phase 2	LY293111 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[67]
Lexacalcitol	DMJ3ZT8	Discontinued in Phase 2	Lexacalcitol decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[32]
LG100268	DM41RK2	Discontinued in Phase 1	LG100268 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[22]
Dioscin	DM5H2W9	Preclinical	Dioscin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[68]
PJ34	DMXO6YH	Preclinical	PJ34 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[69]
Acteoside	DM0YHKB	Terminated	Acteoside decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[70]
EHT-1864	DMYAMP5	Terminated	EHT-1864 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[71]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[72]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[73]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[74]
Coumarin	DM0N8ZM	Investigative	Coumarin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[75]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[76]
Deguelin	DMXT7WG	Investigative	Deguelin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[77]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[78]
methyl p-hydroxybenzoate	DMO58UW	Investigative	methyl p-hydroxybenzoate affects the expression of G1/S-specific cyclin-E1 (CCNE1).	[79]
Glyphosate	DM0AFY7	Investigative	Glyphosate decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[80]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[81]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[82]
U0126	DM31OGF	Investigative	U0126 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[64]
BRN-3548355	DM4KXT0	Investigative	BRN-3548355 increases the expression of G1/S-specific cyclin-E1 (CCNE1).	[83]
15-deoxy-Delta(12, 14)-prostaglandin J(2)	DM8VUX3	Investigative	15-deoxy-Delta(12, 14)-prostaglandin J(2) decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[22]
Apicidin	DM83WVF	Investigative	Apicidin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[84]
GW-3965	DMG60ET	Investigative	GW-3965 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[85]
N-nonylphenol	DMH3OUX	Investigative	N-nonylphenol decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[86]
gingerol	DMNXYSM	Investigative	gingerol decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[87]
Naringin	DM4DG1Y	Investigative	Naringin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[89]
Tyrphostin Ag-1478	DM87ZIH	Investigative	Tyrphostin Ag-1478 decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[26]
Acacetin	DMQOB0X	Investigative	Acacetin decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[90]
3-acetyl-11-keto-beta-boswellic acid	DMGO2D7	Investigative	3-acetyl-11-keto-beta-boswellic acid decreases the expression of G1/S-specific cyclin-E1 (CCNE1).	[91]

2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Afimoxifene	DMFORDT	Phase 2	Afimoxifene increases the cleavage of G1/S-specific cyclin-E1 (CCNE1).	[51]
NMS-873	DMYKZ6U	Investigative	NMS-873 increases the stability of G1/S-specific cyclin-E1 (CCNE1).	[88]

References

• [1] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [2] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [3] Retinoic acid regulates cell cycle progression and cell differentiation in human monocytic THP-1 cells. Exp Cell Res. 2004 Jul 1;297(1):68-81. doi: 10.1016/j.yexcr.2004.02.017.
• [4] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [5] KMTase Set7/9 is a critical regulator of E2F1 activity upon genotoxic stress. Cell Death Differ. 2014 Dec;21(12):1889-99. doi: 10.1038/cdd.2014.108. Epub 2014 Aug 15.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [8] Estrogen-induced G1/S transition of G0-arrested estrogen-dependent breast cancer cells is regulated by mitochondrial oxidant signaling. Oncogene. 2005 Jul 21;24(31):4883-93. doi: 10.1038/sj.onc.1208667.
• [9] Application of cDNA microarray to the study of arsenic-induced liver diseases in the population of Guizhou, China. Toxicol Sci. 2001 Jan;59(1):185-92.
• [10] 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.
• [11] [P27(Kip1), cyclin E and endogenous TGF-beta1 changes in apoptosis of NB4 cells induced by As(2)O(3) and/or TGF-beta1 and their significance]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2009 Feb;17(1):74-9.
• [12] Comparing histone deacetylase inhibitor responses in genetically engineered mouse lung cancer models and a window of opportunity trial in patients with lung cancer. Mol Cancer Ther. 2013 Aug;12(8):1545-55. doi: 10.1158/1535-7163.MCT-12-0933. Epub 2013 May 16.
• [13] 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.
• [14] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [15] Rare sugar D-allose enhances anti-tumor effect of 5-fluorouracil on the human hepatocellular carcinoma cell line HuH-7. J Biosci Bioeng. 2008 Sep;106(3):248-52. doi: 10.1263/jbb.106.248.
• [16] Estrogen receptor regulates E2F1 expression to mediate tamoxifen resistance. Mol Cancer Res. 2010 Mar;8(3):343-52. doi: 10.1158/1541-7786.MCR-09-0395. Epub 2010 Mar 9.
• [17] Effects of folate deficiency on gene expression in the apoptosis and cancer pathways in colon cancer cells. Carcinogenesis. 2006 May;27(5):916-24. doi: 10.1093/carcin/bgi312. Epub 2005 Dec 16.
• [18] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [19] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [20] Cannabidiol enhances cytotoxicity of anti-cancer drugs in human head and neck squamous cell carcinoma. Sci Rep. 2020 Nov 26;10(1):20622. doi: 10.1038/s41598-020-77674-y.
• [21] Troglitazone suppresses cell growth of KU812 cells independently of PPARgamma. Eur J Pharmacol. 2002 Feb 1;436(1-2):7-13. doi: 10.1016/s0014-2999(01)01577-1.
• [22] Thiazolidinediones inhibit proliferation of microvascular and macrovascular cells by a PPARgamma-independent mechanism. Diabetologia. 2005 Mar;48(3):586-94. doi: 10.1007/s00125-005-1672-z. Epub 2005 Feb 24.
• [23] Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.
• [24] Activation of 5-lipoxygenase is required for nicotine mediated epithelial-mesenchymal transition and tumor cell growth. Cancer Lett. 2010 Jun 28;292(2):237-45.
• [25] The protective effects of the antioxidant N-acetylcysteine (NAC) against oxidative stress-associated apoptosis evoked by the organophosphorus insecticide malathion in normal human astrocytes. Toxicology. 2019 Apr 1;417:1-14.
• [26] DNA topoisomerase I is a cofactor for c-Jun in the regulation of epidermal growth factor receptor expression and cancer cell proliferation. Mol Cell Biol. 2005 Jun;25(12):5040-51. doi: 10.1128/MCB.25.12.5040-5051.2005.
• [27] Sulindac induces specific degradation of the HPV oncoprotein E7 and causes growth arrest and apoptosis in cervical carcinoma cells. Cancer Lett. 2007 Jan 8;245(1-2):103-11. doi: 10.1016/j.canlet.2005.12.034. Epub 2006 Feb 20.
• [28] Daunorubicin-induced variations in gene transcription: commitment to proliferation arrest, senescence and apoptosis. Biochem J. 2003 Jun 15;372(Pt 3):703-11. doi: 10.1042/BJ20021950.
• [29] 3,5,3'-triiodothyronine (T3) is a survival factor for pancreatic beta-cells undergoing apoptosis. J Cell Physiol. 2006 Feb;206(2):309-21. doi: 10.1002/jcp.20460.
• [30] The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents, IV: The mechanisms involved in inhibiting cell-cycle progression. Blood. 2001 Aug 1;98(3):842-50. doi: 10.1182/blood.v98.3.842.
• [31] Fluoxetine mediates G0/G1 arrest by inducing functional inhibition of cyclin dependent kinase subunit (CKS)1. Biochem Pharmacol. 2008 May 15;75(10):1924-34. doi: 10.1016/j.bcp.2008.02.013. Epub 2008 Feb 17.
• [32] Inhibition of MG-63 cell cycle progression by synthetic vitamin D3 analogs mediated by p27, Cdk2, cyclin E, and the retinoblastoma protein. Biochem Pharmacol. 2003 Aug 1;66(3):495-504. doi: 10.1016/s0006-2952(03)00283-1.
• [33] Orlistat Displays Antitumor Activity and Enhances the Efficacy of Paclitaxel in Human Hepatoma Hep3B Cells. Chem Res Toxicol. 2019 Feb 18;32(2):255-264. doi: 10.1021/acs.chemrestox.8b00269. Epub 2019 Jan 22.
• [34] Ciprofloxacin mediated cell growth inhibition, S/G2-M cell cycle arrest, and apoptosis in a human transitional cell carcinoma of the bladder cell line. Clin Cancer Res. 2000 Mar;6(3):891-900.
• [35] A retinoid X receptor (RXR)-selective retinoid reveals that RXR-alpha is potentially a therapeutic target in breast cancer cell lines, and that it potentiates antiproliferative and apoptotic responses to peroxisome proliferator-activated receptor ligands. Breast Cancer Res. 2004;6(5):R546-55. doi: 10.1186/bcr913. Epub 2004 Jul 23.
• [36] Dihydroorotate dehydrogenase inhibitor A771726 (leflunomide) induces apoptosis and diminishes proliferation of multiple myeloma cells. Mol Cancer Ther. 2009 Feb;8(2):366-75. doi: 10.1158/1535-7163.MCT-08-0664. Epub 2009 Jan 27.
• [37] Homoharringtonine suppresses LoVo cell growth by inhibiting EphB4 and the PI3K/AKT and MAPK/EKR1/2 signaling pathways. Food Chem Toxicol. 2020 Feb;136:110960. doi: 10.1016/j.fct.2019.110960. Epub 2019 Nov 11.
• [38] Mitotic arrest induced by XK469, a novel antitumor agent, is correlated with the inhibition of cyclin B1 ubiquitination. Int J Cancer. 2002 Jan 1;97(1):121-8. doi: 10.1002/ijc.1570.
• [39] G1 cell cycle arrest by amlodipine, a dihydropyridine Ca2+ channel blocker, in human epidermoid carcinoma A431 cells. Biochem Pharmacol. 2007 Apr 1;73(7):943-53. doi: 10.1016/j.bcp.2006.12.011. Epub 2006 Dec 14.
• [40] Gene expression signature of parathion-transformed human breast epithelial cells. Int J Mol Med. 2007 May;19(5):741-50.
• [41] Tetracaine hydrochloride induces cell cycle arrest in melanoma by downregulating hnRNPA1. Toxicol Appl Pharmacol. 2022 Jan 1;434:115810. doi: 10.1016/j.taap.2021.115810. Epub 2021 Nov 23.
• [42] Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells. Mol Cancer Ther. 2006 Feb;5(2):296-308. doi: 10.1158/1535-7163.MCT-05-0448.
• [43] Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. Int J Cancer. 2008 Jul 1;123(1):41-50. doi: 10.1002/ijc.23485.
• [44] Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines. J Androl. 2007 Mar-Apr;28(2):282-93. doi: 10.2164/jandrol.106.000968. Epub 2006 Oct 18.
• [45] Curcumin suppresses AP1 transcription factor-dependent differentiation and activates apoptosis in human epidermal keratinocytes. J Biol Chem. 2007 Mar 2;282(9):6707-15. doi: 10.1074/jbc.M606003200. Epub 2006 Dec 5.
• [46] Camptothecin induces c-Myc- and Sp1-mediated hTERT expression in LNCaP cells: Involvement of reactive oxygen species and PI3K/Akt. Food Chem Toxicol. 2019 May;127:53-60. doi: 10.1016/j.fct.2019.03.001. Epub 2019 Mar 6.
• [47] Andrographolide causes apoptosis via inactivation of STAT3 and Akt and potentiates antitumor activity of gemcitabine in pancreatic cancer. Toxicol Lett. 2013 Sep 12;222(1):23-35. doi: 10.1016/j.toxlet.2013.06.241. Epub 2013 Jul 8.
• [48] Molecular targets and anticancer potential of indole-3-carbinol and its derivatives. Cell Cycle. 2005 Sep;4(9):1201-15. doi: 10.4161/cc.4.9.1993. Epub 2005 Sep 6.
• [49] Bergapten induces G1 arrest and pro-apoptotic cascade in colorectal cancer cells associating with p53/p21/PTEN axis. Environ Toxicol. 2019 Mar;34(3):303-311. doi: 10.1002/tox.22685. Epub 2018 Dec 21.
• [50] Characterization of 9-nitrocamptothecin liposomes: anticancer properties and mechanisms on hepatocellular carcinoma in vitro and in vivo. PLoS One. 2011;6(6):e21064. doi: 10.1371/journal.pone.0021064. Epub 2011 Jun 9.
• [51] 4-Hydroxytamoxifen-stimulated processing of cyclin E is mediated via G protein-coupled receptor 30 (GPR30) and accompanied by enhanced migration in MCF-7 breast cancer cells. Toxicology. 2013 Jul 5;309:61-5. doi: 10.1016/j.tox.2013.04.012. Epub 2013 Apr 25.
• [52] Retinoic acid stimulates the cell cycle machinery in normal T cells: involvement of retinoic acid receptor-mediated IL-2 secretion. J Immunol. 2002 Nov 15;169(10):5555-63. doi: 10.4049/jimmunol.169.10.5555.
• [53] 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.
• [54] The novel dual PI3K/mTOR inhibitor GDC-0941 synergizes with the MEK inhibitor U0126 in non-small cell lung cancer cells. Mol Med Rep. 2012 Feb;5(2):503-8. doi: 10.3892/mmr.2011.682. Epub 2011 Nov 16.
• [55] Abrogation of p21 expression by flavopiridol enhances depsipeptide-mediated apoptosis in malignant pleural mesothelioma cells. Clin Cancer Res. 2004 Mar 1;10(5):1813-25. doi: 10.1158/1078-0432.ccr-0901-3.
• [56] Ursolic acid induces autophagy in U87MG cells via ROS-dependent endoplasmic reticulum stress. Chem Biol Interact. 2014 Jul 25;218:28-41. doi: 10.1016/j.cbi.2014.04.017. Epub 2014 May 5.
• [57] RWJ-241947 (MCC-555), a unique peroxisome proliferator-activated receptor-gamma ligand with antitumor activity against human prostate cancer in vitro and in beige/nude/ X-linked immunodeficient mice and enhancement of apoptosis in myeloma cells induced by arsenic trioxide. Clin Cancer Res. 2004 Feb 15;10(4):1508-20. doi: 10.1158/1078-0432.ccr-0476-03.
• [58] 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.
• [59] Sorafenib triggers antiproliferative and pro-apoptotic signals in human esophageal adenocarcinoma cells. Dig Dis Sci. 2008 Dec;53(12):3055-64. doi: 10.1007/s10620-008-0294-y. Epub 2008 May 30.
• [60] The BET inhibitor INCB054329 reduces homologous recombination efficiency and augments PARP inhibitor activity in ovarian cancer. Gynecol Oncol. 2018 Jun;149(3):575-584. doi: 10.1016/j.ygyno.2018.03.049. Epub 2018 Mar 20.
• [61] The repression of E2F-1 is critical for the activity of Minerval against cancer. J Pharmacol Exp Ther. 2005 Oct;315(1):466-74. doi: 10.1124/jpet.105.088716. Epub 2005 Jul 18.
• [62] 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.
• [63] Targeting the epigenetic readers in Ewing sarcoma inhibits the oncogenic transcription factor EWS/Fli1. Oncotarget. 2016 Apr 26;7(17):24125-40. doi: 10.18632/oncotarget.8214.
• [64] Differentiation-inducing factor-1-induced growth arrest of K562 leukemia cells involves the reduction of ERK1/2 activity. Eur J Pharmacol. 2004 Feb 6;485(1-3):21-9. doi: 10.1016/j.ejphar.2003.11.041.
• [65] Ribavirin inhibits colorectal cancer growth by downregulating PRMT5 expression and H3R8me2s and H4R3me2s accumulation. Toxicol Appl Pharmacol. 2021 Mar 15;415:115450. doi: 10.1016/j.taap.2021.115450. Epub 2021 Feb 9.
• [66] 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.
• [67] Leukotriene B4 receptor inhibitor LY293111 induces cell cycle arrest and apoptosis in human anaplastic large-cell lymphoma cells via JNK phosphorylation. Leukemia. 2005 Nov;19(11):1977-84. doi: 10.1038/sj.leu.2403929.
• [68] Dioscin inhibits human endometrial carcinoma proliferation via G0/G1 cell cycle arrest and mitochondrial-dependent signaling pathway. Food Chem Toxicol. 2021 Feb;148:111941. doi: 10.1016/j.fct.2020.111941. Epub 2020 Dec 24.
• [69] Small PARP inhibitor PJ-34 induces cell cycle arrest and apoptosis of adult T-cell leukemia cells. J Hematol Oncol. 2015 Oct 23;8:117. doi: 10.1186/s13045-015-0217-2.
• [70] Acteoside inhibits human promyelocytic HL-60 leukemia cell proliferation via inducing cell cycle arrest at G0/G1 phase and differentiation into monocyte. Carcinogenesis. 2007 Sep;28(9):1928-36. doi: 10.1093/carcin/bgm126. Epub 2007 Jul 18.
• [71] Rac GTPases in acute myeloid leukemia cells: Expression profile and biological effects of pharmacological inhibition. Toxicol Appl Pharmacol. 2022 May 1;442:115990. doi: 10.1016/j.taap.2022.115990. Epub 2022 Mar 22.
• [72] Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
• [73] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [74] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [75] A synthetic coumarin derivative (4-flourophenylacetamide-acetyl coumarin) impedes cell cycle at G0/G1 stage, induces apoptosis, and inhibits metastasis via ROS-mediated p53 and AKT signaling pathways in A549 cells. J Biochem Mol Toxicol. 2020 Oct;34(10):e22553. doi: 10.1002/jbt.22553. Epub 2020 Jun 24.
• [76] Deciphering the molecular mechanism underlying anticancer activity of coumestrol in triple-negative breast cancer cells. Toxicol In Vitro. 2018 Feb;46:19-28. doi: 10.1016/j.tiv.2017.10.007. Epub 2017 Oct 3.
• [77] Deguelin exerts anticancer activity of human gastric cancer MGC-803 and MKN-45 cells in vitro. Int J Mol Med. 2018 Jun;41(6):3157-3166. doi: 10.3892/ijmm.2018.3532. Epub 2018 Mar 5.
• [78] 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.
• [79] Differential effect of methyl-, butyl- and propylparaben and 17-estradiol on selected cell cycle and apoptosis gene and protein expression in MCF-7 breast cancer cells and MCF-10A non-malignant cells. J Appl Toxicol. 2014 Sep;34(9):1041-50. doi: 10.1002/jat.2978. Epub 2014 Jan 30.
• [80] 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.
• [81] Anti-leukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-B inactivation. Toxicol In Vitro. 2012 Apr;26(3):396-405.
• [82] 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.
• [83] The cigarette smoke components induced the cell proliferation and epithelial to mesenchymal transition via production of reactive oxygen species in endometrial adenocarcinoma cells. Food Chem Toxicol. 2018 Nov;121:657-665. doi: 10.1016/j.fct.2018.09.023. Epub 2018 Sep 17.
• [84] Modulation of cell cycles and apoptosis by apicidin in estrogen receptor (ER)-positive and-negative human breast cancer cells. Chem Biol Interact. 2008 Apr 15;172(3):235-44. doi: 10.1016/j.cbi.2008.01.007. Epub 2008 Feb 1.
• [85] System analysis of cross-talk between nuclear receptors reveals an opposite regulation of the cell cycle by LXR and FXR in human HepaRG liver cells. PLoS One. 2019 Aug 22;14(8):e0220894. doi: 10.1371/journal.pone.0220894. eCollection 2019.
• [86] Influence of hexabromocyclododecane and 4-nonylphenol on the regulation of cell growth, apoptosis and migration in prostatic cancer cells. Toxicol In Vitro. 2016 Apr;32:240-7. doi: 10.1016/j.tiv.2016.01.008. Epub 2016 Jan 19.
• [87] Assessment of anti-cancerous potential of 6-gingerol (Tongling White Ginger) and its synergy with drugs on human cervical adenocarcinoma cells. Food Chem Toxicol. 2017 Nov;109(Pt 2):910-922. doi: 10.1016/j.fct.2017.02.038. Epub 2017 Feb 27.
• [88] Covalent and allosteric inhibitors of the ATPase VCP/p97 induce cancer cell death. Nat Chem Biol. 2013 Sep;9(9):548-56. doi: 10.1038/nchembio.1313. Epub 2013 Jul 28.
• [89] Requirement for Ras/Raf/ERK pathway in naringin-induced G1-cell-cycle arrest via p21WAF1 expression. Carcinogenesis. 2008 Sep;29(9):1701-9. doi: 10.1093/carcin/bgn055. Epub 2008 Feb 22.
• [90] Acacetin induces sustained ERK1/2 activation and RIP1-dependent necroptotic death in breast cancer cells. Toxicol Appl Pharmacol. 2023 Mar 1;462:116409. doi: 10.1016/j.taap.2023.116409. Epub 2023 Feb 3.
• [91] 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.
• [92] Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer. Clin Cancer Res. 2011 Mar 15;17(6):1591-602. doi: 10.1158/1078-0432.CCR-10-2307. Epub 2011 Jan 28.
• [93] Response to inhibition of smoothened in diverse epithelial cancer cells that lack smoothened or patched 1 mutations. Int J Oncol. 2012 Nov;41(5):1751-61. doi: 10.3892/ijo.2012.1599. Epub 2012 Aug 22.