Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP9XG86)

• DOT Name: Tumor necrosis factor receptor superfamily member 6 (FAS)
• Synonyms: Apo-1 antigen; Apoptosis-mediating surface antigen FAS; FASLG receptor; CD antigen CD95
• Gene Name: FAS
• Related Disease:
  Autoimmune lymphoproliferative syndrome type 1
  Autoimmune lymphoproliferative syndrome
• UniProt ID: TNR6_HUMAN
• PDB ID: 1DDF; 2NA7; 3EWT; 3EZQ; 3THM; 3TJE
• Pfam ID: PF00531 ; PF00020
• Sequence:
  MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCH
  KPCPPGERKARDCTVNGDEPDCVPCQEGKEYTDKAHFSSKCRRCRLCDEGHGLEVEINCT
  RTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGIIKECTLTSNTKCKEEGSRSNLGWLCLL
  LLPIPLIVWVKRKEVQKTCRKHRKENQGSHESPTLNPETVAINLSDVDLSKYITTIAGVM
  TLSQVKGFVRKNGVNEAKIDEIKNDNVQDTAEQKVQLLRNWHQLHGKKEAYDTLIKDLKK
  ANLCTLAEKIQTIILKDITSDSENSNFRNEIQSLV
• Function: Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase CASP8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs CASP8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro).
• Tissue Specificity: Isoform 1 and isoform 6 are expressed at equal levels in resting peripheral blood mononuclear cells. After activation there is an increase in isoform 1 and decrease in the levels of isoform 6.
• KEGG Pathway:
  Platinum drug resistance (hsa01524)
  MAPK sig.ling pathway (hsa04010)
  Cytokine-cytokine receptor interaction (hsa04060)
  p53 sig.ling pathway (hsa04115)
  Apoptosis (hsa04210)
  Necroptosis (hsa04217)
  .tural killer cell mediated cytotoxicity (hsa04650)
  TNF sig.ling pathway (hsa04668)
  Non-alcoholic fatty liver disease (hsa04932)
  Alcoholic liver disease (hsa04936)
  Type I diabetes mellitus (hsa04940)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Pathogenic Escherichia coli infection (hsa05130)
  Chagas disease (hsa05142)
  African trypanosomiasis (hsa05143)
  Hepatitis C (hsa05160)
  Hepatitis B (hsa05161)
  Measles (hsa05162)
  Human cytomegalovirus infection (hsa05163)
  Influenza A (hsa05164)
  Human papillomavirus infection (hsa05165)
  Kaposi sarcoma-associated herpesvirus infection (hsa05167)
  Herpes simplex virus 1 infection (hsa05168)
  Epstein-Barr virus infection (hsa05169)
  Human immunodeficiency virus 1 infection (hsa05170)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Autoimmune thyroid disease (hsa05320)
  Allograft rejection (hsa05330)
  Graft-versus-host disease (hsa05332)
  Lipid and atherosclerosis (hsa05417)
• Reactome Pathway:
  Regulation by c-FLIP (R-HSA-3371378)
  RIPK1-mediated regulated necrosis (R-HSA-5213460)
  CASP8 activity is inhibited (R-HSA-5218900)
  TP53 Regulates Transcription of Death Receptors and Ligands (R-HSA-6803211)
  Dimerization of procaspase-8 (R-HSA-69416)
  FasL/ CD95L signaling (R-HSA-75157)
  Caspase activation via Death Receptors in the presence of ligand (R-HSA-140534)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autoimmune lymphoproliferative syndrome type 1	DISAFGRA	Definitive	Autosomal dominant	[1]
Autoimmune lymphoproliferative syndrome	DISUG5ES	Supportive	Autosomal dominant	[2]

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Taurine	DMVW7N3	Investigative	Tumor necrosis factor receptor superfamily member 6 (FAS) increases the secretion of Taurine.	[80]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[9]
Estradiol	DMUNTE3	Approved	Estradiol increases the mutagenesis of Tumor necrosis factor receptor superfamily member 6 (FAS).	[10]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[11]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[12]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[13]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[14]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[15]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[17]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[18]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[19]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[20]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[21]
Menadione	DMSJDTY	Approved	Menadione increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[15]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[22]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[23]
Folic acid	DMEMBJC	Approved	Folic acid affects the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[24]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[25]
Bortezomib	DMNO38U	Approved	Bortezomib decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[26]
Troglitazone	DM3VFPD	Approved	Troglitazone increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[27]
Hydroquinone	DM6AVR4	Approved	Hydroquinone increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[28]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[27]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[29]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[30]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[31]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[32]
Paclitaxel	DMLB81S	Approved	Paclitaxel decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[33]
Diclofenac	DMPIHLS	Approved	Diclofenac affects the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[19]
Nicotine	DMWX5CO	Approved	Nicotine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[34]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[35]
Mitomycin	DMH0ZJE	Approved	Mitomycin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[36]
Permethrin	DMZ0Q1G	Approved	Permethrin decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[37]
Cidofovir	DMA13GD	Approved	Cidofovir affects the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[38]
Cocaine	DMSOX7I	Approved	Cocaine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[39]
Topotecan	DMP6G8T	Approved	Topotecan decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[20]
Gemcitabine	DMSE3I7	Approved	Gemcitabine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[40]
Fenofibrate	DMFKXDY	Approved	Fenofibrate decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[38]
Mitoxantrone	DMM39BF	Approved	Mitoxantrone increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[41]
Cyclophosphamide	DM4O2Z7	Approved	Cyclophosphamide decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[42]
Clodronate	DM9Y6X7	Approved	Clodronate decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[38]
Capsaicin	DMGMF6V	Approved	Capsaicin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[43]
Alitretinoin	DMME8LH	Approved	Alitretinoin decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[5]
Ibuprofen	DM8VCBE	Approved	Ibuprofen decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[38]
Daunorubicin	DMQUSBT	Approved	Daunorubicin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[41]
Clorgyline	DMCEUJD	Approved	Clorgyline increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[44]
Acocantherin	DM7JT24	Approved	Acocantherin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[45]
Thalidomide	DM70BU5	Approved	Thalidomide decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[46]
Hydroxyurea	DMOQVU9	Approved	Hydroxyurea increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[47]
Beta-carotene	DM0RXBT	Approved	Beta-carotene increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[5]
Adefovir dipivoxil	DMMAWY1	Approved	Adefovir dipivoxil increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[38]
Docetaxel	DMDI269	Approved	Docetaxel increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[48]
Nitric Oxide	DM1RBYG	Approved	Nitric Oxide increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[49]
Bezafibrate	DMZDCS0	Approved	Bezafibrate increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[50]
Ardeparin	DMYRX8B	Approved	Ardeparin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[51]
Melatonin	DMKWFBT	Approved	Melatonin decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[52]
Vitamin A	DMJ2AH4	Approved	Vitamin A decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[5]
Artesunate	DMR27C8	Approved	Artesunate increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[53]
Orlistat	DMRJSP8	Approved	Orlistat decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[54]
Eicosapentaenoic acid/docosa-hexaenoic acid	DMMUCG4	Approved	Eicosapentaenoic acid/docosa-hexaenoic acid decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[55]
Fructose	DM43AN2	Approved	Fructose decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[56]
Chlorambucil	DMRKE63	Approved	Chlorambucil increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[57]
Heroin diacetylmorphine	DMDBWHY	Approved	Heroin diacetylmorphine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[39]
Masoprocol	DMMVNZ0	Approved	Masoprocol increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[58]
Epinephrine	DM3KJBC	Approved	Epinephrine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[59]
Fludarabine	DMVRLT7	Approved	Fludarabine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[57]
Pemetrexed	DMMX2E6	Approved	Pemetrexed increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[60]
Acitretin	DM8BKU9	Approved	Acitretin increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[61]
Octreotide	DMHIDCJ	Approved	Octreotide increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[62]
Vismodegib	DM5IXKQ	Approved	Vismodegib increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[63]
Regorafenib	DMHSY1I	Approved	Regorafenib increases the activity of Tumor necrosis factor receptor superfamily member 6 (FAS).	[64]
Raltitrexed	DMT9K8G	Approved	Raltitrexed increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[32]
Fotemustine	DMV62ED	Approved	Fotemustine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[65]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[67]
Berberine	DMC5Q8X	Phase 4	Berberine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[68]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[69]
Resveratrol	DM3RWXL	Phase 3	Resveratrol increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[70]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the activity of Tumor necrosis factor receptor superfamily member 6 (FAS).	[71]
Chlorpromazine	DMBGZI3	Phase 3 Trial	Chlorpromazine increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[72]
HMPL-004	DM29XGY	Phase 3	HMPL-004 increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[73]
Genistein	DM0JETC	Phase 2/3	Genistein decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[74]
Phenol	DM1QSM3	Phase 2/3	Phenol increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[75]
Amsilarotene	DMOB01U	Phase 2	Amsilarotene increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[76]
CF102	DMP56WJ	Phase 2	CF102 increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[77]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[42]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[78]
LY294002	DMY1AFS	Phase 1	LY294002 decreases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[33]
AMEP	DMFELMQ	Phase 1	AMEP increases the expression of Tumor necrosis factor receptor superfamily member 6 (FAS).	[79]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Idelalisib	DM602WT	Approved	Idelalisib affects the response to substance of Tumor necrosis factor receptor superfamily member 6 (FAS).	[66]
Bay 80-6946	DMLOS5R	Approved	Bay 80-6946 affects the response to substance of Tumor necrosis factor receptor superfamily member 6 (FAS).	[66]
GDC-0068	DMWBZJD	Phase 3	GDC-0068 affects the response to substance of Tumor necrosis factor receptor superfamily member 6 (FAS).	[66]
GSK2110183	DMZHB37	Phase 2	GSK2110183 affects the response to substance of Tumor necrosis factor receptor superfamily member 6 (FAS).	[66]
MK-2206	DMT1OZ6	Phase 2	MK-2206 affects the response to substance of Tumor necrosis factor receptor superfamily member 6 (FAS).	[66]
GSK2141795	DMSHE70	Phase 2	GSK2141795 affects the response to substance of Tumor necrosis factor receptor superfamily member 6 (FAS).	[66]
ARQ 092	DM5WK0J	Phase 2	ARQ 092 affects the response to substance of Tumor necrosis factor receptor superfamily member 6 (FAS).	[66]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency in adults. Haematologica. 2013 Mar;98(3):389-92. doi: 10.3324/haematol.2012.067488. Epub 2012 Sep 14.
• [3] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [4] 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.
• [5] Beta-carotene and apocarotenals promote retinoid signaling in BEAS-2B human bronchioepithelial cells. Arch Biochem Biophys. 2006 Nov 1;455(1):48-60.
• [6] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [7] Breast cancer cells response to the antineoplastic agents cisplatin, carboplatin, and doxorubicin at the mRNA expression levels of distinct apoptosis-related genes, including the new member, BCL2L12. Ann N Y Acad Sci. 2007 Jan;1095:35-44. doi: 10.1196/annals.1397.005.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Toxicogenomics-based discrimination of toxic mechanism in HepG2 human hepatoma cells. Toxicol Sci. 2000 Dec;58(2):399-415.
• [10] Estrogen directly activates AID transcription and function. J Exp Med. 2009 Jan 16;206(1):99-111. doi: 10.1084/jem.20080521. Epub 2009 Jan 12.
• [11] 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.
• [12] Inorganic arsenic exposure increased expression of Fas and Bax gene in vivo and vitro. Gene. 2018 Sep 10;671:135-141. doi: 10.1016/j.gene.2018.05.121. Epub 2018 Jun 1.
• [13] Multifaceted preventive effects of single agent quercetin on a human prostate adenocarcinoma cell line (PC-3): implications for nutritional transcriptomics and multi-target therapy. Med Oncol. 2011 Dec;28(4):1395-404. doi: 10.1007/s12032-010-9603-3. Epub 2010 Jul 2.
• [14] [Impact of arsenic trioxide on proliferation and metastasis of drug-resistant human ovarian carcinoma cell line]. Ai Zheng. 2002 Aug;21(8):863-7.
• [15] Gene expression after treatment with hydrogen peroxide, menadione, or t-butyl hydroperoxide in breast cancer cells. Cancer Res. 2002 Nov 1;62(21):6246-54.
• [16] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [17] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [18] Primary Human Hepatocyte Spheroids as Tools to Study the Hepatotoxic Potential of Non-Pharmaceutical Chemicals. Int J Mol Sci. 2021 Oct 12;22(20):11005. doi: 10.3390/ijms222011005.
• [19] 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.
• [20] Topotecan and methotrexate alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells. Biol Chem. 2006 Dec;387(12):1629-33. doi: 10.1515/BC.2006.203.
• [21] Effect of zoledronic acid on oral fibroblasts and epithelial cells: a potential mechanism of bisphosphonate-associated osteonecrosis. Br J Haematol. 2009 Mar;144(5):667-76. doi: 10.1111/j.1365-2141.2008.07504.x. Epub 2008 Nov 20.
• [22] 5-Fluorouracil: identification of novel downstream mediators of tumour response. Anticancer Res. 2004 Mar-Apr;24(2A):417-23.
• [23] [A study on the heterogeneous apoptosis of lymphocytes, eosinophils, and neutrophils from peripheral blood of asthmatic patients]. Zhonghua Jie He He Hu Xi Za Zhi. 2003 Oct;26(10):610-4.
• [24] In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes. Br J Nutr. 2006 May;95(5):870-8. doi: 10.1079/bjn20051579.
• [25] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [26] Synergistic antiproliferative effect of arsenic trioxide combined with bortezomib in HL60 cell line and primary blasts from patients affected by myeloproliferative disorders. Cancer Genet Cytogenet. 2010 Jun;199(2):110-20. doi: 10.1016/j.cancergencyto.2010.02.010.
• [27] Regulatory role of KEAP1 and NRF2 in PPAR expression and chemoresistance in human non-small-cell lung carcinoma cells. Free Radic Biol Med. 2012 Aug 15;53(4):758-68. doi: 10.1016/j.freeradbiomed.2012.05.041. Epub 2012 Jun 7.
• [28] Phenolic metabolites of benzene induced caspase-dependent cytotoxicities to K562 cells accompanied with decrease in cell surface sialic acids. Environ Toxicol. 2014 Dec;29(12):1437-51. doi: 10.1002/tox.21874. Epub 2013 Jun 17.
• [29] Development and validation of the TGx-HDACi transcriptomic biomarker to detect histone deacetylase inhibitors in human TK6 cells. Arch Toxicol. 2021 May;95(5):1631-1645. doi: 10.1007/s00204-021-03014-2. Epub 2021 Mar 26.
• [30] 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.
• [31] Cell death mechanisms of the anti-cancer drug etoposide on human cardiomyocytes isolated from pluripotent stem cells. Arch Toxicol. 2018 Apr;92(4):1507-1524.
• [32] Effect of p53 status and STAT1 on chemotherapy-induced, Fas-mediated apoptosis in colorectal cancer. Cancer Res. 2005 Oct 1;65(19):8951-60. doi: 10.1158/0008-5472.CAN-05-0961.
• [33] Cacalol, a natural sesquiterpene, induces apoptosis in breast cancer cells by modulating Akt-SREBP-FAS signaling pathway. Breast Cancer Res Treat. 2011 Jul;128(1):57-68. doi: 10.1007/s10549-010-1076-8. Epub 2010 Jul 28.
• [34] Upregulation of Fas and FasL expression in nicotine-induced apoptosis of endothelial cells. Methods Find Exp Clin Pharmacol. 2010 Jan-Feb;32(1):13-8. doi: 10.1358/mf.2010.32.1.1428742.
• [35] 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.
• [36] Influence of antitumor drugs on the expression of Fas system in SW480 colon cancer cells. Eur J Gastroenterol Hepatol. 2006 Oct;18(10):1071-7. doi: 10.1097/01.meg.0000231750.68513.6c.
• [37] Permethrin and ivermectin modulate lipid metabolism in steatosis-induced HepG2 hepatocyte. Food Chem Toxicol. 2019 Mar;125:595-604. doi: 10.1016/j.fct.2019.02.005. Epub 2019 Feb 6.
• [38] Transcriptomics hit the target: monitoring of ligand-activated and stress response pathways for chemical testing. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):7-18.
• [39] Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse. Neuropsychopharmacology. 2006 Oct;31(10):2304-12. doi: 10.1038/sj.npp.1301089. Epub 2006 May 3.
• [40] Gemcitabine-induced apoptosis in 5637 cell line: an in-vitro model for high-risk superficial bladder cancer. Anticancer Drugs. 2007 Feb;18(2):179-85. doi: 10.1097/CAD.0b013e328010ef47.
• [41] Identification of genomic biomarkers for anthracycline-induced cardiotoxicity in human iPSC-derived cardiomyocytes: an in vitro repeated exposure toxicity approach for safety assessment. Arch Toxicol. 2016 Nov;90(11):2763-2777.
• [42] Transcriptome-based functional classifiers for direct immunotoxicity. Arch Toxicol. 2014 Mar;88(3):673-89.
• [43] Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. Carcinogenesis. 2009 Aug;30(8):1320-9. doi: 10.1093/carcin/bgp138. Epub 2009 Jun 5.
• [44] Anti-oncogenic and pro-differentiation effects of clorgyline, a monoamine oxidase A inhibitor, on high grade prostate cancer cells. BMC Med Genomics. 2009 Aug 20;2:55. doi: 10.1186/1755-8794-2-55.
• [45] Ouabain induces apoptotic cell death in human prostate DU 145 cancer cells through DNA damage and TRAIL pathways. Environ Toxicol. 2019 Dec;34(12):1329-1339. doi: 10.1002/tox.22834. Epub 2019 Aug 21.
• [46] Stimulation of erythropoiesis by thalidomide in multiple myeloma patients: its influence on FasL, TRAIL and their receptors on erythroblasts. Haematologica. 2006 Mar;91(3):386-9.
• [47] Hydroxyurea (HU)-induced apoptosis in the mouse fetal lung. Exp Mol Pathol. 2005 Aug;79(1):59-67. doi: 10.1016/j.yexmp.2005.02.007. Epub 2005 Apr 22.
• [48] [The mechanism of docetaxel-induced apoptosis in human lung cancer cells]. Zhonghua Zhong Liu Za Zhi. 2000 May;22(3):208-11.
• [49] Apoptotic signaling pathways induced by nitric oxide in human lymphoblastoid cells expressing wild-type or mutant p53. Cancer Res. 2004 May 1;64(9):3022-9. doi: 10.1158/0008-5472.can-03-1880.
• [50] CYP4A11 is repressed by retinoic acid in human liver cells. FEBS Lett. 2006 Jun 12;580(14):3361-7.
• [51] In vitro determination of the apoptotic effect of heparin on lymphoblasts using DNA analysis and measurements of Fas and Bcl-2 proteins by flow cytometry. Pediatr Hematol Oncol. 2004 Jul-Aug;21(5):383-91. doi: 10.1080/08880010490457051.
• [52] Melatonin protects CD4+ T cells from activation-induced cell death by blocking NFAT-mediated CD95 ligand upregulation. J Immunol. 2010 Apr 1;184(7):3487-94. doi: 10.4049/jimmunol.0902961. Epub 2010 Feb 24.
• [53] Combination treatment of malignant B cells using the anti-CD20 antibody rituximab and the anti-malarial artesunate. Int J Oncol. 2009 Jul;35(1):149-58.
• [54] Diosgenin and 4-Hydroxyisoleucine from Fenugreek Are Regulators of Genes Involved in Lipid Metabolism in The Human Colorectal Cancer Cell Line SW480. Cell J. 2021 Jan;22(4):514-522. doi: 10.22074/cellj.2021.6751. Epub 2020 Apr 22.
• [55] The effect of combination treatment with docosahexaenoic acid and 5-fluorouracil on the mRNA expression of apoptosis-related genes, including the novel gene BCL2L12, in gastric cancer cells. In Vitro Cell Dev Biol Anim. 2009 Jan-Feb;45(1-2):69-74. doi: 10.1007/s11626-008-9154-5. Epub 2008 Nov 18.
• [56] Non-nutritional sweeteners effects on endothelial vascular function. Toxicol In Vitro. 2020 Feb;62:104694. doi: 10.1016/j.tiv.2019.104694. Epub 2019 Oct 23.
• [57] Caspase 8 activation independent of Fas (CD95/APO-1) signaling may mediate killing of B-chronic lymphocytic leukemia cells by cytotoxic drugs or gamma radiation. Blood. 2001 Nov 1;98(9):2800-7. doi: 10.1182/blood.v98.9.2800.
• [58] Lipoxygenase inhibitors induce death receptor 5/TRAIL-R2 expression and sensitize malignant tumor cells to TRAIL-induced apoptosis. Cancer Sci. 2007 Sep;98(9):1417-23. doi: 10.1111/j.1349-7006.2007.00559.x. Epub 2007 Jul 23.
• [59] Carvedilol prevents epinephrine-induced apoptosis in human coronary artery endothelial cells: modulation of Fas/Fas ligand and caspase-3 pathway. Cardiovasc Res. 2000 Feb;45(3):788-94. doi: 10.1016/s0008-6363(99)00369-7.
• [60] The roles of thymidylate synthase and p53 in regulating Fas-mediated apoptosis in response to antimetabolites. Clin Cancer Res. 2004 May 15;10(10):3562-71. doi: 10.1158/1078-0432.CCR-03-0532.
• [61] Acitretin induces apoptosis through CD95 signalling pathway in human cutaneous squamous cell carcinoma cell line SCL-1. J Cell Mol Med. 2009 Sep;13(9A):2888-98. doi: 10.1111/j.1582-4934.2008.00397.x. Epub 2009 Jun 20.
• [62] [Octreotide induces apoptosis of human hepatoma cells by the mechanism of facilitating the Fas/FasL gene expression therein]. Zhonghua Yi Xue Za Zhi. 2008 Mar 11;88(10):716-8.
• [63] Hedgehog signaling antagonist GDC-0449 (Vismodegib) inhibits pancreatic cancer stem cell characteristics: molecular mechanisms. PLoS One. 2011;6(11):e27306. doi: 10.1371/journal.pone.0027306. Epub 2011 Nov 8.
• [64] Regorefenib induces extrinsic/intrinsic apoptosis and inhibits MAPK/NF-B-modulated tumor progression in bladder cancer in vitro and in vivo. Environ Toxicol. 2019 Jun;34(6):679-688. doi: 10.1002/tox.22734. Epub 2019 Feb 25.
• [65] Translesion polymerase is upregulated by cancer therapeutics and confers anticancer drug resistance. Cancer Res. 2014 Oct 1;74(19):5585-96. doi: 10.1158/0008-5472.CAN-14-0953. Epub 2014 Aug 14.
• [66] PI3K/AKT inhibitors aggravate death receptor-mediated hepatocyte apoptosis and liver injury. Toxicol Appl Pharmacol. 2019 Oct 15;381:114729. doi: 10.1016/j.taap.2019.114729. Epub 2019 Aug 22.
• [67] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [68] Cytotoxicity of berberine on human cervical carcinoma HeLa cells through mitochondria, death receptor and MAPK pathways, and in-silico drug-target prediction. Toxicol In Vitro. 2010 Sep;24(6):1482-90. doi: 10.1016/j.tiv.2010.07.017. Epub 2010 Jul 23.
• [69] 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.
• [70] Experimental and computational studies on newly synthesized resveratrol derivative: a new method for cancer chemoprevention and therapeutics?. OMICS. 2013 Nov;17(11):568-83. doi: 10.1089/omi.2013.0014. Epub 2013 Sep 17.
• [71] Expression of the retinoic acid-metabolizing enzyme CYP26A1 limits programmed cell death. Mol Pharmacol. 2005 May;67(5):1808-17. doi: 10.1124/mol.104.005769. Epub 2005 Feb 9.
• [72] Effects of chlorpromazine with and without UV irradiation on gene expression of HepG2 cells. Mutat Res. 2005 Aug 4;575(1-2):47-60. doi: 10.1016/j.mrfmmm.2005.03.002. Epub 2005 Apr 26.
• [73] Andrographolide sensitizes the cytotoxicity of human colorectal carcinoma cells toward cisplatin via enhancing apoptosis pathways in vitro and in vivo. Toxicol Sci. 2014 May;139(1):108-20. doi: 10.1093/toxsci/kfu032. Epub 2014 Feb 22.
• [74] A high concentration of genistein down-regulates activin A, Smad3 and other TGF-beta pathway genes in human uterine leiomyoma cells. Exp Mol Med. 2012 Apr 30;44(4):281-92.
• [75] Classification of heavy-metal toxicity by human DNA microarray analysis. Environ Sci Technol. 2007 May 15;41(10):3769-74.
• [76] 4- [3,5-bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) induced fas expression and activated caspase-3 and -8 in a DLD-1 colon cancer cell line. In Vivo. 2007 Mar-Apr;21(2):381-7.
• [77] p53-Independent induction of Fas and apoptosis in leukemic cells by an adenosine derivative, Cl-IB-MECA. Biochem Pharmacol. 2002 Mar 1;63(5):871-80. doi: 10.1016/s0006-2952(02)00839-0.
• [78] The BET bromodomain inhibitor JQ1 suppresses growth of pancreatic ductal adenocarcinoma in patient-derived xenograft models. Oncogene. 2016 Feb 18;35(7):833-45.
• [79] 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.
• [80] The involvement of caspases in the CD95(Fas/Apo-1)- but not swelling-induced cellular taurine release from Jurkat T-lymphocytes. Pflugers Arch. 2000 May;440(1):93-9. doi: 10.1007/s004240000247.