Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0LUO47)

• DOT Name: Tumor protein p73 (TP73)
• Synonyms: p53-like transcription factor; p53-related protein
• Gene Name: TP73
• Related Disease:
  Ependymoma
  Glioma
  Pancreatic cancer
  Wilms tumor
  Acute lymphocytic leukaemia
  Adenocarcinoma
  Adenoma
  Adult lymphoma
  Bladder cancer
  Bone osteosarcoma
  Carcinoma
  Carcinoma of esophagus
  Ciliary dyskinesia, primary, 47, and lissencephaly
  Clear cell renal carcinoma
  Colon carcinoma
  Colorectal carcinoma
  Congenital nervous system disorder
  Esophageal cancer
  Head-neck squamous cell carcinoma
  Lymphoma, non-Hodgkin, familial
  Metastatic malignant neoplasm
  Myocardial infarction
  Neoplasm of esophagus
  Non-hodgkin lymphoma
  Non-small-cell lung cancer
  Osteosarcoma
  Otitis media
  Pediatric lymphoma
  Plasma cell myeloma
  Renal cell carcinoma
  Small lymphocytic lymphoma
  Urinary bladder cancer
  Urinary bladder neoplasm
  Adult glioblastoma
  Adult T-cell leukemia/lymphoma
  Breast neoplasm
  Childhood acute lymphoblastic leukemia
  Lung neoplasm
  Triple negative breast cancer
  Colon cancer
  Acute myelogenous leukaemia
  B-cell neoplasm
  Cervical cancer
  Cervical carcinoma
  Hepatitis C virus infection
  Prostate cancer
  Prostate carcinoma
  Small-cell lung cancer
• UniProt ID: P73_HUMAN
• PDB ID: 1COK; 1DXS; 2KBY; 2MPS; 2NB1; 2WQI; 2WQJ; 2WTT; 2XWC; 3VD0; 3VD1; 3VD2; 4A63; 4G82; 4G83; 4GUO; 4GUQ; 5HOB; 5HOC; 5KBD; 6FGS; 6IJQ; 7EZJ; 8P9C; 8P9D; 8P9E
• Pfam ID: PF00870 ; PF07710 ; PF07647
• Sequence:
  MAQSTATSPDGGTTFEHLWSSLEPDSTYFDLPQSSRGNNEVVGGTDSSMDVFHLEGMTTS
  VMAQFNLLSSTMDQMSSRAASASPYTPEHAASVPTHSPYAQPSSTFDTMSPAPVIPSNTD
  YPGPHHFEVTFQQSSTAKSATWTYSPLLKKLYCQIAKTCPIQIKVSTPPPPGTAIRAMPV
  YKKAEHVTDVVKRCPNHELGRDFNEGQSAPASHLIRVEGNNLSQYVDDPVTGRQSVVVPY
  EPPQVGTEFTTILYNFMCNSSCVGGMNRRPILIIITLEMRDGQVLGRRSFEGRICACPGR
  DRKADEDHYREQQALNESSAKNGAASKRAFKQSPPAVPALGAGVKKRRHGDEDTYYLQVR
  GRENFEILMKLKESLELMELVPQPLVDSYRQQQQLLQRPSHLQPPSYGPVLSPMNKVHGG
  MNKLPSVNQLVGQPPPHSSAATPNLGPVGPGMLNNHGHAVPANGEMSSSHSAQSMVSGSH
  CTPPPPYHADPSLVSFLTGLGCPNCIEYFTSQGLQSIYHLQNLTIEDLGALKIPEQYRMT
  IWRGLQDLKQGHDYSTAQQLLRSSNAATISIGGSGELQRQRVMEAVHFRVRHTITIPNRG
  GPGGGPDEWADFGFDLPDCKARKQPIKEEFTEAEIH
• Function: Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. Is an activator of FOXJ1 expression. It is an essential factor for the positive regulation of lung ciliated cell differentiation.
• Tissue Specificity: Expressed in striatal neurons of patients with Huntington disease (at protein level). Brain, kidney, placenta, colon, heart, liver, spleen, skeletal muscle, prostate, thymus and pancreas. Highly expressed in fetal tissue. Expressed in the respiratory epithelium .
• KEGG Pathway:
  p53 sig.ling pathway (hsa04115)
  Hippo sig.ling pathway (hsa04390)
  Neurotrophin sig.ling pathway (hsa04722)
  Measles (hsa05162)
• Reactome Pathway:
  TP53 Regulates Transcription of Genes Involved in Cytochrome C Release (R-HSA-6803204)
  TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain (R-HSA-6803205)
  TP53 Regulates Transcription of Caspase Activators and Caspases (R-HSA-6803207)
  TP53 Regulates Transcription of Death Receptors and Ligands (R-HSA-6803211)
  Regulation of TP53 Activity through Association with Co-factors (R-HSA-6804759)
  RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236)
  Activation of PUMA and translocation to mitochondria (R-HSA-139915)

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ependymoma	DISUMRNZ	Definitive	Genetic Variation	[1]
Glioma	DIS5RPEH	Definitive	Altered Expression	[2]
Pancreatic cancer	DISJC981	Definitive	Altered Expression	[3]
Wilms tumor	DISB6T16	Definitive	Altered Expression	[4]
Acute lymphocytic leukaemia	DISPX75S	Strong	Biomarker	[5]
Adenocarcinoma	DIS3IHTY	Strong	Altered Expression	[6]
Adenoma	DIS78ZEV	Strong	Genetic Variation	[7]
Adult lymphoma	DISK8IZR	Strong	Biomarker	[8]
Bladder cancer	DISUHNM0	Strong	Altered Expression	[9]
Bone osteosarcoma	DIST1004	Strong	Altered Expression	[10]
Carcinoma	DISH9F1N	Strong	Biomarker	[9]
Carcinoma of esophagus	DISS6G4D	Strong	Biomarker	[11]
Ciliary dyskinesia, primary, 47, and lissencephaly	DISKTDLG	Strong	Autosomal recessive	[12]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[13]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[14]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[15]
Congenital nervous system disorder	DIS2BIP8	Strong	Biomarker	[16]
Esophageal cancer	DISGB2VN	Strong	Biomarker	[11]
Head-neck squamous cell carcinoma	DISF7P24	Strong	Genetic Variation	[17]
Lymphoma, non-Hodgkin, familial	DISCXYIZ	Strong	Biomarker	[8]
Metastatic malignant neoplasm	DIS86UK6	Strong	Altered Expression	[18]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[19]
Neoplasm of esophagus	DISOLKAQ	Strong	Biomarker	[11]
Non-hodgkin lymphoma	DISS2Y8A	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[20]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[10]
Otitis media	DISGZDUO	Strong	Biomarker	[21]
Pediatric lymphoma	DIS51BK2	Strong	Biomarker	[8]
Plasma cell myeloma	DIS0DFZ0	Strong	Altered Expression	[22]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[13]
Small lymphocytic lymphoma	DIS30POX	Strong	Biomarker	[23]
Urinary bladder cancer	DISDV4T7	Strong	Altered Expression	[9]
Urinary bladder neoplasm	DIS7HACE	Strong	Altered Expression	[9]
Adult glioblastoma	DISVP4LU	moderate	Altered Expression	[24]
Adult T-cell leukemia/lymphoma	DIS882XU	moderate	Biomarker	[25]
Breast neoplasm	DISNGJLM	moderate	Biomarker	[26]
Childhood acute lymphoblastic leukemia	DISJ5D6U	moderate	Posttranslational Modification	[27]
Lung neoplasm	DISVARNB	moderate	Biomarker	[26]
Triple negative breast cancer	DISAMG6N	moderate	Biomarker	[28]
Colon cancer	DISVC52G	Disputed	Biomarker	[29]
Acute myelogenous leukaemia	DISCSPTN	Limited	Genetic Variation	[30]
B-cell neoplasm	DISVY326	Limited	Biomarker	[31]
Cervical cancer	DISFSHPF	Limited	Biomarker	[32]
Cervical carcinoma	DIST4S00	Limited	Biomarker	[32]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[33]
Prostate cancer	DISF190Y	Limited	Biomarker	[34]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[34]
Small-cell lung cancer	DISK3LZD	Limited	SomaticCausalMutation	[35]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Tumor protein p73 (TP73) affects the response to substance of Fluorouracil.	[60]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Tumor protein p73 (TP73).	[36]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Tumor protein p73 (TP73).	[37]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Tumor protein p73 (TP73).	[40]
Decitabine	DMQL8XJ	Approved	Decitabine decreases the methylation of Tumor protein p73 (TP73).	[43]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Tumor protein p73 (TP73).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Tumor protein p73 (TP73).	[50]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin increases the expression of Tumor protein p73 (TP73).	[38]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tumor protein p73 (TP73).	[39]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor protein p73 (TP73).	[41]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tumor protein p73 (TP73).	[42]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Tumor protein p73 (TP73).	[38]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor protein p73 (TP73).	[45]
Bexarotene	DMOBIKY	Approved	Bexarotene increases the expression of Tumor protein p73 (TP73).	[46]
Etretinate	DM2CZFA	Approved	Etretinate increases the expression of Tumor protein p73 (TP73).	[46]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tumor protein p73 (TP73).	[47]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor protein p73 (TP73).	[48]
Selinexor	DMBD4K3	Phase 3	Selinexor increases the expression of Tumor protein p73 (TP73).	[49]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tumor protein p73 (TP73).	[51]
Flavonoid derivative 1	DMCQP0B	Patented	Flavonoid derivative 1 increases the expression of Tumor protein p73 (TP73).	[52]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Tumor protein p73 (TP73).	[53]
Nickel chloride	DMI12Y8	Investigative	Nickel chloride decreases the activity of Tumor protein p73 (TP73).	[54]
Phencyclidine	DMQBEYX	Investigative	Phencyclidine increases the expression of Tumor protein p73 (TP73).	[55]
4-hydroxy-2-nonenal	DM2LJFZ	Investigative	4-hydroxy-2-nonenal increases the expression of Tumor protein p73 (TP73).	[56]
Rapamycin Immunosuppressant Drug	DM678IB	Investigative	Rapamycin Immunosuppressant Drug increases the expression of Tumor protein p73 (TP73).	[57]
Chrysin	DM7V2LG	Investigative	Chrysin increases the expression of Tumor protein p73 (TP73).	[52]
Kaempferol	DMHEMUB	Investigative	Kaempferol increases the expression of Tumor protein p73 (TP73).	[52]
Apigenin	DMI3491	Investigative	Apigenin increases the expression of Tumor protein p73 (TP73).	[58]
PD98059	DMZC90M	Investigative	PD98059 increases the expression of Tumor protein p73 (TP73).	[59]
Myricetin	DMTV4L0	Investigative	Myricetin increases the expression of Tumor protein p73 (TP73).	[58]
CI-1040	DMF3DZX	Investigative	CI-1040 increases the expression of Tumor protein p73 (TP73).	[59]

References

• [1] Aberrant promoter methylation of multiple genes in oligodendrogliomas and ependymomas.Cancer Genet Cytogenet. 2003 Jul 15;144(2):134-42. doi: 10.1016/s0165-4608(02)00928-7.
• [2] si-TP73-AS1 suppressed proliferation and increased the chemotherapeutic response of GC cells to cisplatin.Oncol Lett. 2018 Sep;16(3):3706-3714. doi: 10.3892/ol.2018.9107. Epub 2018 Jul 10.
• [3] The effects of curcumin on proliferation, apoptosis, invasion, and NEDD4 expression in pancreatic cancer.Biochem Pharmacol. 2017 Sep 15;140:28-40. doi: 10.1016/j.bcp.2017.05.014. Epub 2017 May 20.
• [4] Expression and clinical significance of p73 in Wilms tumor in children.Oncol Lett. 2019 Jun;17(6):5435-5440. doi: 10.3892/ol.2019.10249. Epub 2019 Apr 15.
• [5] Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia cell apoptosis.Cell Signal. 2011 Jan;23(1):152-60. doi: 10.1016/j.cellsig.2010.08.015. Epub 2010 Aug 31.
• [6] p73 isoforms can induce T-cell factor-dependent transcription in gastrointestinal cells.Cancer Res. 2004 Sep 15;64(18):6390-3. doi: 10.1158/0008-5472.CAN-04-2176.
• [7] Promoter hypermethylation profile of cell cycle regulator genes in pituitary adenomas.J Neurooncol. 2007 Jun;83(2):153-62. doi: 10.1007/s11060-006-9316-9. Epub 2007 Jan 11.
• [8] TP73, an under-appreciated player in non-Hodgkin lymphoma pathogenesis and management.Curr Mol Med. 2014 May;14(4):432-9. doi: 10.2174/1566524014666140414204458.
• [9] Expression of p53 family genes in urinary bladder cancer: correlation with disease aggressiveness and recurrence.Tumour Biol. 2014 Mar;35(3):2481-9. doi: 10.1007/s13277-013-1328-4. Epub 2013 Nov 11.
• [10] Panobinostat mediated cell death: a novel therapeutic approach for osteosarcoma.Oncotarget. 2018 Aug 31;9(68):32997-33010. doi: 10.18632/oncotarget.26038. eCollection 2018 Aug 31.
• [11] Cinobufagin Promotes Cell Cycle Arrest and Apoptosis to Block Human Esophageal Squamous Cell Carcinoma Cells Growth via the p73 Signalling Pathway.Biol Pharm Bull. 2019;42(9):1500-1509. doi: 10.1248/bpb.b19-00174.
• [12] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [13] Analysis of p73 expression pattern in acute myeloid leukemias: lack of DeltaN-p73 expression is a frequent feature of acute promyelocytic leukemia.Leukemia. 2004 Nov;18(11):1804-9. doi: 10.1038/sj.leu.2403483.
• [14] Np73 status in peritoneal and ovarian dissemination of appendicular adenocarcinoids (goblet cells).Clin Transl Oncol. 2019 Oct;21(10):1432-1439. doi: 10.1007/s12094-019-02091-1.
• [15] Genetic variants in p53 signaling pathway genes predict chemotherapy efficacy in colorectal cancer.Cancer Med. 2019 Jul;8(7):3428-3436. doi: 10.1002/cam4.2215. Epub 2019 May 15.
• [16] TAp73 knockout mice show morphological and functional nervous system defects associated with loss of p75 neurotrophin receptor. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):18952-7. doi: 10.1073/pnas.1221172110. Epub 2013 Nov 4.
• [17] Genetic variants of the p53 and p73 genes jointly increase risk of second primary malignancies in patients after index squamous cell carcinoma of the head and neck.Cancer. 2012 Jan 15;118(2):485-92. doi: 10.1002/cncr.26222. Epub 2011 Jun 29.
• [18] Restin suppressed epithelial-mesenchymal transition and tumor metastasis in breast cancer cells through upregulating mir-200a/b expression via association with p73.Mol Cancer. 2015 May 14;14:102. doi: 10.1186/s12943-015-0370-9.
• [19] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [20] Differential expressions of MDM2 and TAP73 in cancer and cancer-adjacent tissues in patients with non-small-cell lung carcinoma.Pulmonology. 2018 Feb 13:S2173-5115(17)30153-7. doi: 10.1016/j.rppnen.2017.08.008. Online ahead of print.
• [21] microRNA-34a regulates neurite outgrowth, spinal morphology, and function.Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21099-104. doi: 10.1073/pnas.1112063108. Epub 2011 Dec 12.
• [22] PRIMA-1Met/APR-246 displays high antitumor activity in multiple myeloma by induction of p73 and Noxa.Mol Cancer Ther. 2013 Nov;12(11):2331-41. doi: 10.1158/1535-7163.MCT-12-1166. Epub 2013 Sep 12.
• [23] Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.Haematologica. 2011 Feb;96(2):323-7. doi: 10.3324/haematol.2010.031161. Epub 2010 Nov 3.
• [24] SIRT2-mediated inactivation of p73 is required for glioblastoma tumorigenicity.EMBO Rep. 2018 Nov;19(11):e45587. doi: 10.15252/embr.201745587. Epub 2018 Sep 13.
• [25] Integrated molecular analysis of adult T cell leukemia/lymphoma.Nat Genet. 2015 Nov;47(11):1304-15. doi: 10.1038/ng.3415. Epub 2015 Oct 5.
• [26] TAp73 upregulates IL-1 in cancer cells: Potential biomarker in lung and breast cancer?.Biochem Biophys Res Commun. 2017 Jan 15;482(3):498-505. doi: 10.1016/j.bbrc.2016.10.085. Epub 2017 Feb 3.
• [27] The role of p73 in hematological malignancies.Leukemia. 2006 May;20(5):757-66. doi: 10.1038/sj.leu.2404166.
• [28] p73 G4C14-to-A4T14 polymorphisms are positively correlated with triple-negative breast cancer in southwestern China.Med Oncol. 2013 Jun;30(2):515. doi: 10.1007/s12032-013-0515-x. Epub 2013 Feb 27.
• [29] Synergistic activation of the NEU4 promoter by p73 and AP2 in colon cancer cells.Sci Rep. 2019 Jan 30;9(1):950. doi: 10.1038/s41598-018-37521-7.
• [30] Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
• [31] Cytoplasmic pro-apoptotic function of the tumor suppressor p73 is mediated through a modified mode of recognition of the anti-apoptotic regulator Bcl-X(L).J Biol Chem. 2018 Dec 21;293(51):19546-19558. doi: 10.1074/jbc.RA118.003061. Epub 2018 Nov 14.
• [32] Inhibition of SF3b1 by pladienolide B evokes cycle arrest, apoptosis induction and p73 splicing in human cervical carcinoma cells.Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):1273-1280. doi: 10.1080/21691401.2019.1596922.
• [33] Physical and functional interaction between HCV core protein and the different p73 isoforms.Oncogene. 2003 May 1;22(17):2573-80. doi: 10.1038/sj.onc.1206333.
• [34] Identification of a novel microRNA-mRNA regulatory biomodule in human prostate cancer.Cell Death Dis. 2018 Feb 21;9(3):301. doi: 10.1038/s41419-018-0293-7.
• [35] Comprehensive genomic profiles of small cell lung cancer.Nature. 2015 Aug 6;524(7563):47-53. doi: 10.1038/nature14664. Epub 2015 Jul 13.
• [36] 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.
• [37] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [38] Differential regulation of vitamin D receptor (VDR) by the p53 Family: p73-dependent induction of VDR upon DNA damage. J Biol Chem. 2007 Oct 12;282(41):29847-54.
• [39] The role of RelA (p65) threonine 505 phosphorylation in the regulation of cell growth, survival, and migration. Mol Biol Cell. 2011 Sep;22(17):3032-40. doi: 10.1091/mbc.E11-04-0280. Epub 2011 Jul 7.
• [40] 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.
• [41] Quercetin and Its Fermented Extract as a Potential Inhibitor of Bisphenol A-Exposed HT-29 Colon Cancer Cells' Viability. Int J Mol Sci. 2023 Mar 15;24(6):5604. doi: 10.3390/ijms24065604.
• [42] Arsenic trioxide induces apoptosis in NB-4, an acute promyelocytic leukemia cell line, through up-regulation of p73 via suppression of nuclear factor kappa B-mediated inhibition of p73 transcription and prevention of NF-kappaB-mediated induction of XIAP, cIAP2, BCL-XL and survivin. Med Oncol. 2010 Sep;27(3):833-42. doi: 10.1007/s12032-009-9294-9. Epub 2009 Sep 10.
• [43] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [44] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [45] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [46] Bexarotene activates the p53/p73 pathway in human cutaneous T-cell lymphoma. Br J Dermatol. 2009 Mar;160(3):519-26. doi: 10.1111/j.1365-2133.2008.08931.x. Epub 2008 Nov 25.
• [47] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [48] Resveratrol exerts antiproliferative activity and induces apoptosis in Waldenstr?m's macroglobulinemia. Clin Cancer Res. 2008 Mar 15;14(6):1849-58. doi: 10.1158/1078-0432.CCR-07-1750.
• [49] The synergy of the XPO1 inhibitors combined with the BET inhibitor INCB057643 in high-grade B-cell lymphoma via downregulation of MYC expression. Sci Rep. 2023 Oct 29;13(1):18554. doi: 10.1038/s41598-023-45721-z.
• [50] 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.
• [51] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [52] Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol. 2008 Jun;46(6):2042-53. doi: 10.1016/j.fct.2008.01.049. Epub 2008 Feb 7.
• [53] Sulforaphane-induced apoptosis in Xuanwei lung adenocarcinoma cell line XWLC-05. Thorac Cancer. 2017 Jan;8(1):16-25. doi: 10.1111/1759-7714.12396. Epub 2016 Nov 23.
• [54] Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells. Biochem Biophys Res Commun. 2015 Jan 2;456(1):29-34. doi: 10.1016/j.bbrc.2014.11.027. Epub 2014 Nov 18.
• [55] Microarray Analysis of Gene Expression Alteration in Human Middle Ear Epithelial Cells Induced by Asian Sand Dust. Clin Exp Otorhinolaryngol. 2015 Dec;8(4):345-53. doi: 10.3342/ceo.2015.8.4.345. Epub 2015 Nov 10.
• [56] 4-Hydroxynonenal modulation of p53 family gene expression in the SK-N-BE neuroblastoma cell line. Free Radic Biol Med. 2005 Jan 15;38(2):215-25. doi: 10.1016/j.freeradbiomed.2004.10.014.
• [57] Differential regulation of the p73 cistrome by mammalian target of rapamycin reveals transcriptional programs of mesenchymal differentiation and tumorigenesis. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2076-81. doi: 10.1073/pnas.1011936108. Epub 2011 Jan 18.
• [58] Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis. Toxicol In Vitro. 2009 Aug;23(5):797-807. doi: 10.1016/j.tiv.2009.04.007. Epub 2009 May 3.
• [59] Treatment with arsenic trioxide (ATO) and MEK1 inhibitor activates the p73-p53AIP1 apoptotic pathway in leukemia cells. Blood. 2004 Jul 15;104(2):519-25. doi: 10.1182/blood-2003-08-2743. Epub 2004 Mar 18.
• [60] Characterization of 5-fluorouracil-resistant cholangiocarcinoma cell lines. Chemotherapy. 2008;54(5):343-51. doi: 10.1159/000151541. Epub 2008 Aug 21.