Details of the Drug Combination

General Information of Drug Combination (ID: DC76ZHD)

• Drug Combination Name: Mechlorethamine + Dactinomycin
• Indication: Carcinoma; Status: Investigative [1]
• Component Drugs:
  Mechlorethamine (DM0CVXA): Small molecular drug
  Dactinomycin (DM2YGNW): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: RXF 393
  Zero Interaction Potency (ZIP) Score: 3.73
  Bliss Independence Score: 8.44
  Loewe Additivity Score: 8.09
  LHighest Single Agent (HSA) Score: 8

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Mechlorethamine

Disease Entry	ICD 11	Status	REF
Chronic myelogenous leukaemia	2A20.0	Approved	[2]
Lung cancer	2C25.0	Approved	[2]
Mycosis fungoides	2B01	Approved	[2]
Primary cutaneous T-cell lymphoma	N.A.	Approved	[2]
Small lymphocytic lymphoma	2A82.0	Approved	[2]
T-cell lymphoma	2A90	Approved	[3]
Hodgkin lymphoma	2B30	Phase 3	[4]
Classic Hodgkin lymphoma	N.A.	Investigative	[2]

Mechlorethamine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Intercalator	[9]

Mechlorethamine Interacts with 19 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Receptor tyrosine-protein kinase erbB-2 (ERBB2)	OTOAUNCK	ERBB2_HUMAN	Decreases Expression	[10]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Decreases Activity	[11]
Transcription factor Jun (JUN)	OTCYBO6X	JUN_HUMAN	Increases Expression	[12]
Cyclin-dependent kinase 1 (CDK1)	OTW1SC2N	CDK1_HUMAN	Decreases Activity	[13]
Glutathione S-transferase A2 (GSTA2)	OTW7UB1H	GSTA2_HUMAN	Increases Expression	[14]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[12]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[15]
G2/mitotic-specific cyclin-B1 (CCNB1)	OT19S7E5	CCNB1_HUMAN	Decreases Activity	[13]
Transcription factor JunB (JUNB)	OTG2JXV5	JUNB_HUMAN	Increases Expression	[12]
Transcription factor JunD (JUND)	OTNKACJD	JUND_HUMAN	Increases Expression	[12]
Cyclin-A2 (CCNA2)	OTPHHYZJ	CCNA2_HUMAN	Increases Stability	[13]
Cyclin-dependent kinase 2 (CDK2)	OTB5DYYZ	CDK2_HUMAN	Increases Activity	[13]
Protein S100-P (S100P)	OTJCXNJG	S100P_HUMAN	Increases Expression	[16]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[17]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Activity	[15]
Caspase-9 (CASP9)	OTD4RFFG	CASP9_HUMAN	Increases Activity	[15]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Decreases Expression	[18]
Bcl-2 homologous antagonist/killer (BAK1)	OTDP6ILW	BAK_HUMAN	Increases Expression	[19]
Transient receptor potential cation channel subfamily A member 1 (TRPA1)	OTRDIR5M	TRPA1_HUMAN	Increases Response To Substance	[20]

Indication(s) of Dactinomycin

Disease Entry	ICD 11	Status	REF
Adult kidney Wilms tumor	N.A.	Approved	[5]
Advanced cancer	2A00-2F9Z	Approved	[5]
Beckwith-Wiedemann syndrome	N.A.	Approved	[5]
Childhood kidney Wilms tumor	N.A.	Approved	[5]
Gestational trophoblastic neoplasia	2F33-2F76	Approved	[5]
Hamartoma	N.A.	Approved	[5]
Solid tumour/cancer	2A00-2F9Z	Approved	[6]
Wilms tumor	N.A.	Approved	[5]

Dactinomycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Breaker	[24]

Dactinomycin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[25]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[26]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[27]

Dactinomycin Interacts with 85 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Response To Substance	[28]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Response To Substance	[29]
Urokinase-type plasminogen activator (PLAU)	OTX0QGKK	UROK_HUMAN	Increases Expression	[21]
Dihydropyrimidinase-related protein 4 (DPYSL4)	OT3SBS2S	DPYL4_HUMAN	Increases Expression	[21]
Integral membrane protein GPR137B (GPR137B)	OT1CINQQ	G137B_HUMAN	Increases Expression	[21]
Integrin alpha-IIb (ITGA2B)	OT4Y17PY	ITA2B_HUMAN	Increases Expression	[21]
Ras-related protein R-Ras (RRAS)	OTBBF28C	RRAS_HUMAN	Increases Expression	[21]
Growth arrest and DNA damage-inducible protein GADD45 alpha (GADD45A)	OTDRV63V	GA45A_HUMAN	Increases Expression	[21]
Stomatin (STOM)	OTC8R6EH	STOM_HUMAN	Increases Expression	[21]
Cellular retinoic acid-binding protein 2 (CRABP2)	OTY01V9G	RABP2_HUMAN	Increases Expression	[21]
Tyrosine-protein kinase receptor UFO (AXL)	OTKA2SUX	UFO_HUMAN	Increases Expression	[21]
14-3-3 protein sigma (SFN)	OTLJCZ1U	1433S_HUMAN	Increases Expression	[21]
Tumor necrosis factor ligand superfamily member 9 (TNFSF9)	OTV9L89D	TNFL9_HUMAN	Increases Expression	[21]
Galectin-7 (LGALS7)	OTMSVI7R	LEG7_HUMAN	Increases Expression	[21]
Large ribosomal subunit protein eL34 (RPL34)	OT0U9VMQ	RL34_HUMAN	Increases Expression	[21]
Rho GDP-dissociation inhibitor 2 (ARHGDIB)	OT9PD6CS	GDIR2_HUMAN	Increases Expression	[21]
Epithelial membrane protein 1 (EMP1)	OTSZHUHQ	EMP1_HUMAN	Increases Expression	[21]
Epithelial membrane protein 3 (EMP3)	OTODMJ1D	EMP3_HUMAN	Increases Expression	[21]
Protein ripply3 (RIPPLY3)	OT1HK35I	DSCR6_HUMAN	Increases Expression	[21]
Endonuclease III-like protein 1 (NTHL1)	OTPQXPT1	NTH_HUMAN	Decreases Expression	[21]
Antigen peptide transporter 1 (TAP1)	OTJL27PW	TAP1_HUMAN	Increases Expression	[21]
Apoptosis regulator BAX (BAX)	OTAW0V4V	BAX_HUMAN	Increases Expression	[21]
Kinesin-like protein KIF1A (KIF1A)	OT3JVEGV	KIF1A_HUMAN	Increases Expression	[21]
Protein AF1q (MLLT11)	OTG5RVHC	AF1Q_HUMAN	Increases Expression	[21]
Laminin subunit gamma-2 (LAMC2)	OTJMTM72	LAMC2_HUMAN	Increases Expression	[21]
Filamin-C (FLNC)	OT3F8J6Y	FLNC_HUMAN	Increases Expression	[21]
Immediate early response gene 5 protein (IER5)	OTJPTXMD	IER5_HUMAN	Increases Expression	[21]
Keratin, type II cytoskeletal 80 (KRT80)	OTAU54U3	K2C80_HUMAN	Increases Expression	[21]
All-trans-retinol 13,14-reductase (RETSAT)	OTC3AOPX	RETST_HUMAN	Increases Expression	[21]
Interleukin-27 receptor subunit alpha (IL27RA)	OTSQBAKI	I27RA_HUMAN	Increases Expression	[21]
Neuropilin and tolloid-like protein 2 (NETO2)	OT0YAMC0	NETO2_HUMAN	Increases Expression	[21]
Mitochondria-eating protein (SPATA18)	OTOEHTHU	MIEAP_HUMAN	Increases Expression	[21]
Phospholipase ABHD3 (ABHD3)	OTH8P977	ABHD3_HUMAN	Increases Expression	[21]
Homer protein homolog 3 (HOMER3)	OTQ6D9X1	HOME3_HUMAN	Increases Expression	[21]
BSD domain-containing protein 1 (BSDC1)	OT853CP9	BSDC1_HUMAN	Increases Expression	[21]
Stathmin-3 (STMN3)	OT20F289	STMN3_HUMAN	Increases Expression	[21]
Endothelial protein C receptor (PROCR)	OTRHED17	EPCR_HUMAN	Increases Expression	[21]
Fatty acid desaturase 3 (FADS3)	OT9RVXGE	FADS3_HUMAN	Increases Expression	[21]
Protein O-mannosyl-transferase 1 (POMT1)	OTGQSHL5	POMT1_HUMAN	Increases Expression	[21]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Decreases Expression	[30]
Tumor protein p53-inducible protein 11 (TP53I11)	OTFPDYZU	P5I11_HUMAN	Decreases Expression	[31]
Tumor necrosis factor receptor superfamily member 10B (TNFRSF10B)	OTA1CPBV	TR10B_HUMAN	Decreases Expression	[32]
CASP8 and FADD-like apoptosis regulator (CFLAR)	OTX14BAS	CFLAR_HUMAN	Decreases Expression	[33]
Mitogen-activated protein kinase kinase kinase 7 (MAP3K7)	OTUXEASC	M3K7_HUMAN	Decreases Expression	[34]
Prominin-1 (PROM1)	OTBHV8NX	PROM1_HUMAN	Decreases Expression	[35]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[34]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Decreases Expression	[36]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Increases Response To Substance	[37]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[38]
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)	OTBPMIMW	G3P_HUMAN	Increases Expression	[34]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[39]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Expression	[40]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[38]
Proto-oncogene tyrosine-protein kinase ROS (ROS1)	OTDSKUGE	ROS1_HUMAN	Increases Expression	[34]
Fibroblast growth factor 2 (FGF2)	OT7YUJ9F	FGF2_HUMAN	Decreases Expression	[41]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Decreases Expression	[42]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[43]
Apoptosis regulator Bcl-2 (BCL2)	OT9DVHC0	BCL2_HUMAN	Decreases Expression	[44]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Decreases Expression	[45]
Matrix metalloproteinase-9 (MMP9)	OTB2QDAV	MMP9_HUMAN	Decreases Expression	[46]
Histone H2AX (H2AX)	OT18UX57	H2AX_HUMAN	Increases Expression	[35]
CCAAT/enhancer-binding protein beta (CEBPB)	OTM9MQIA	CEBPB_HUMAN	Decreases Expression	[34]
Nuclear factor NF-kappa-B p105 subunit (NFKB1)	OTNRRD8I	NFKB1_HUMAN	Decreases Expression	[34]
Lamin-B1 (LMNB1)	OT100T3P	LMNB1_HUMAN	Decreases Expression	[34]
rRNA 2'-O-methyltransferase fibrillarin (FBL)	OTRODIE5	FBRL_HUMAN	Affects Localization	[47]
DNA-directed RNA polymerase II subunit RPB1 (POLR2A)	OTHJQ1DZ	RPB1_HUMAN	Decreases Phosphorylation	[48]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[49]
Signal transducer and activator of transcription 1-alpha/beta (STAT1)	OTLMBUZ6	STAT1_HUMAN	Increases Expression	[34]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Decreases Expression	[34]
Caspase-2 (CASP2)	OTUDYSPP	CASP2_HUMAN	Increases Cleavage	[50]
Dual specificity mitogen-activated protein kinase kinase 4 (MAP2K4)	OTZPZX11	MP2K4_HUMAN	Decreases Expression	[34]
Caspase-7 (CASP7)	OTAPJ040	CASP7_HUMAN	Decreases Expression	[34]
DNA repair protein RAD51 homolog 1 (RAD51)	OTNVWGC1	RAD51_HUMAN	Decreases Expression	[51]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Decreases Expression	[52]
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	OT2YYI1A	MCL1_HUMAN	Decreases Expression	[53]
Son of sevenless homolog 1 (SOS1)	OTTCWXC3	SOS1_HUMAN	Decreases Expression	[34]
FAS-associated death domain protein (FADD)	OTV7GFHH	FADD_HUMAN	Decreases Expression	[34]
Growth arrest-specific protein 6 (GAS6)	OTPOPUUE	GAS6_HUMAN	Increases Degradation	[54]
Caspase-8 (CASP8)	OTA8TVI8	CASP8_HUMAN	Decreases Expression	[34]
Bcl-2-binding component 3, isoforms 3/4 (BBC3)	OTUAXDAY	BBC3B_HUMAN	Increases Expression	[44]
Proheparin-binding EGF-like growth factor (HBEGF)	OTLU00JS	HBEGF_HUMAN	Decreases Expression	[41]
Transcription factor SOX-17 (SOX17)	OT9H4WWE	SOX17_HUMAN	Decreases Localization	[55]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[35]
Hyaluronidase-1 (HYAL1)	OT2SJN0X	HYAL1_HUMAN	Increases ADR	[56]
Complement component 1 Q subcomponent-binding protein, mitochondrial (C1QBP)	OTPYQX3K	C1QBP_HUMAN	Decreases Response To Substance	[57]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Adult acute myeloid leukemia	DC1ZO3V	HL-60(TB)	Investigative	[58]
Adult T acute lymphoblastic leukemia	DCM30V3	MOLT-4	Investigative	[58]
Anaplastic large cell lymphoma	DC6YS82	SR	Investigative	[58]
Astrocytoma	DC10ZTP	SNB-19	Investigative	[58]
Childhood T acute lymphoblastic leukemia	DCDM3YB	CCRF-CEM	Investigative	[58]
Glioma	DCQEB4V	SF-268	Investigative	[58]
Papillary renal cell carcinoma	DCWGE68	ACHN	Investigative	[58]
Plasma cell myeloma	DCAZ2N1	RPMI-8226	Investigative	[58]
Breast adenocarcinoma	DCGOIX9	MDA-MB-468	Investigative	[1]
Colon adenocarcinoma	DCWEMUW	COLO 205	Investigative	[1]
Invasive ductal carcinoma	DC7ZVPT	HS 578T	Investigative	[1]
Invasive ductal carcinoma	DCOLKZG	BT-549	Investigative	[1]
Adenocarcinoma	DC2XZKR	HCT116	Investigative	[59]
Adenocarcinoma	DCYR82L	HCC-2998	Investigative	[59]
Adenocarcinoma	DCK9FB2	SW-620	Investigative	[59]
Cutaneous melanoma	DCTA2O7	SK-MEL-28	Investigative	[59]
High grade ovarian serous adenocarcinoma	DCUOX2Z	OVCAR-4	Investigative	[59]
High grade ovarian serous adenocarcinoma	DCZKOWT	OVCAR-8	Investigative	[59]
High grade ovarian serous adenocarcinoma	DCQ6A3F	OVCAR-5	Investigative	[59]
Large cell lung carcinoma	DCVI4VN	NCI-H460	Investigative	[59]
Lung adenocarcinoma	DCXN3JB	EKVX	Investigative	[59]
Lung adenocarcinoma	DCUBZFC	NCI-H522	Investigative	[59]
Malignant melanoma	DCO5I5Q	LOX IMVI	Investigative	[59]
Malignant melanoma	DCUVSSU	UACC62	Investigative	[59]
Melanoma	DCWPTDK	MALME-3M	Investigative	[59]
Non-small cell lung carcinoma	DCUNV22	HOP-92	Investigative	[59]
Ovarian serous cystadenocarcinoma	DC1P9EM	SK-OV-3	Investigative	[59]

References

• [1] Biologically active neutrophil chemokine pattern in tonsillitis.Clin Exp Immunol. 2004 Mar;135(3):511-8. doi: 10.1111/j.1365-2249.2003.02390.x.
• [2] Mechlorethamine FDA Label
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7218).
• [5] Dactinomycin FDA Label
• [6] FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 050682.
• [7] Thioredoxin Cross-Linking by Nitrogen Mustard in Lung Epithelial Cells: Formation of Multimeric Thioredoxin/Thioredoxin Reductase Complexes and Inhibition of Disulfide Reduction. Chem Res Toxicol. 2015 Nov 16;28(11):2091-103. doi: 10.1021/acs.chemrestox.5b00194. Epub 2015 Oct 19.
• [8] Cross-linking of thioredoxin reductase by the sulfur mustard analogue mechlorethamine (methylbis(2-chloroethyl)amine) in human lung epithelial cells and rat lung: selective inhibition of disulfide reduction but not redox cycling. Chem Res Toxicol. 2014 Jan 21;27(1):61-75. doi: 10.1021/tx400329a. Epub 2013 Dec 9.
• [9] Proteomic analysis of DNA-protein cross-linking by antitumor nitrogen mustards. Chem Res Toxicol. 2009 Jun;22(6):1151-62.
• [10] Down-regulation of HER-2 expression in human breast cancer cell HBC-4 and ZR75-1 by nitrogen-mustard-N-oxide. Kobe J Med Sci. 2007;53(4):135-42.
• [11] Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022 Apr 18;35(4):636-650. doi: 10.1021/acs.chemrestox.1c00420. Epub 2022 Mar 21.
• [12] Nitrogen mustard prevents transport of Fra-1 into the nucleus to promote c-Fos- and FosB-dependent IL-8 induction in injured mouse epidermis. Toxicol Lett. 2020 Feb 1;319:256-263. doi: 10.1016/j.toxlet.2019.10.006. Epub 2019 Oct 19.
• [13] G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently. J Biol Chem. 1993 Apr 15;268(11):8298-308.
• [14] Overexpression of GSTA2 protects against cell cycle arrest and apoptosis induced by the DNA inter-strand crosslinking nitrogen mustard, mechlorethamine. J Cell Biochem. 2005 May 15;95(2):339-51. doi: 10.1002/jcb.20440.
• [15] Inhibition of caspase-dependent mitochondrial permeability transition protects airway epithelial cells against mustard-induced apoptosis. Apoptosis. 2006 Sep;11(9):1545-59. doi: 10.1007/s10495-006-8764-1.
• [16] S100P is selectively upregulated in tumor cell lines challenged with DNA cross-linking agents. Leuk Res. 2005 Oct;29(10):1181-90. doi: 10.1016/j.leukres.2005.03.012.
• [17] Ebselen reduces the toxicity of mechlorethamine in A-431 cells via inhibition of apoptosis. J Biochem Mol Toxicol. 2013 Jun;27(6):313-22. doi: 10.1002/jbt.21490. Epub 2013 May 6.
• [18] Histopathologic and immunohistochemical features in human skin after exposure to nitrogen and sulfur mustard. Am J Dermatopathol. 1998 Feb;20(1):22-8. doi: 10.1097/00000372-199802000-00005.
• [19] Increased expression of VDAC1 sensitizes carcinoma cells to apoptosis induced by DNA cross-linking agents. Biochem Pharmacol. 2012 May 1;83(9):1172-82. doi: 10.1016/j.bcp.2012.01.017. Epub 2012 Jan 21.
• [20] Activation of the human TRPA1 channel by different alkylating sulfur and nitrogen mustards and structurally related chemotherapeutic drugs. Toxicol Lett. 2023 Mar 1;376:51-59. doi: 10.1016/j.toxlet.2023.01.007. Epub 2023 Jan 21.
• [21] Genomic profiling uncovers a molecular pattern for toxicological characterization of mutagens and promutagens in vitro. Toxicol Sci. 2011 Jul;122(1):185-97.
• [22] Synergy is achieved by complementation with Apo2L/TRAIL and actinomycin D in Apo2L/TRAIL-mediated apoptosis of prostate cancer cells: role of XIAP in resistance. Prostate. 2002 Dec 1;53(4):286-99. doi: 10.1002/pros.10155.
• [23] Endocrine disruptors fludioxonil and fenhexamid stimulate miR-21 expression in breast cancer cells. Toxicol Sci. 2013 Jan;131(1):71-83. doi: 10.1093/toxsci/kfs290. Epub 2012 Oct 10.
• [24] Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
• [25] Expression of multidrug resistance-associated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution. Cancer Res. 1995 Nov 15;55(22):5342-7.
• [26] Potential role of drug transporters in the pathogenesis of medically intractable epilepsy. Epilepsia. 2005 Feb;46(2):224-35.
• [27] Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Mol Pharmacol. 2003 Jan;63(1):65-72.
• [28] Functional analysis of MRP1 cloned from bovine. FEBS Lett. 2002 Jun 19;521(1-3):211-3. doi: 10.1016/s0014-5793(02)02816-8.
• [29] Establishment and characterization of new cellular lymphoma model expressing transgenic human MDR1. Leuk Res. 2005 Apr;29(4):407-14. doi: 10.1016/j.leukres.2004.09.001.
• [30] Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells. Arch Toxicol. 2019 Jan;93(1):121-136.
• [31] Possible roles of a tumor suppressor gene PIG11 in hepatocarcinogenesis and As2O3-induced apoptosis in liver cancer cells. J Gastroenterol. 2009;44(5):460-9. doi: 10.1007/s00535-009-0030-1. Epub 2009 Apr 1.
• [32] Death receptor regulation and celecoxib-induced apoptosis in human lung cancer cells. J Natl Cancer Inst. 2004 Dec 1;96(23):1769-80. doi: 10.1093/jnci/djh322.
• [33] Combination of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and actinomycin D induces apoptosis even in TRAIL-resistant human pancreatic cancer cells. Clin Cancer Res. 2001 Feb;7(2):407-14.
• [34] Response rate of fibrosarcoma cells to cytotoxic drugs on the expression level correlates to the therapeutic response rate of fibrosarcomas and is mediated by regulation of apoptotic pathways. BMC Cancer. 2005 Jul 7;5:74. doi: 10.1186/1471-2407-5-74.
• [35] Actinomycin D inhibits the expression of the cystine/glutamate transporter xCT via attenuation of CD133 synthesis in CD133(+) HCC. Chem Biol Interact. 2019 Aug 25;309:108713. doi: 10.1016/j.cbi.2019.06.026. Epub 2019 Jun 19.
• [36] Ascorbic acid enhances low-density lipoprotein receptor expression by suppressing proprotein convertase subtilisin/kexin 9 expression. J Biol Chem. 2020 Nov 20;295(47):15870-15882. doi: 10.1074/jbc.RA120.015623. Epub 2020 Sep 10.
• [37] Heme oxygenase-1-derived carbon monoxide requires the activation of transcription factor NF-kappa B to protect endothelial cells from tumor necrosis factor-alpha-mediated apoptosis. J Biol Chem. 2002 May 17;277(20):17950-61. doi: 10.1074/jbc.M108317200. Epub 2002 Mar 5.
• [38] The effects of particulate wear debris, cytokines, and growth factors on the functions of MG-63 osteoblasts. J Bone Joint Surg Am. 2001 Feb;83(2):201-11. doi: 10.2106/00004623-200102000-00007.
• [39] The effect of potent iron chelators on the regulation of p53: examination of the expression, localization and DNA-binding activity of p53 and the transactivation of WAF1. Carcinogenesis. 2003 Oct;24(10):1601-14. doi: 10.1093/carcin/bgg116. Epub 2003 Jul 17.
• [40] T-2 toxin upregulates the expression of human cytochrome P450 1A1 (CYP1A1) by enhancing NRF1 and Sp1 interaction. Toxicol Lett. 2019 Oct 15;315:77-86. doi: 10.1016/j.toxlet.2019.08.021. Epub 2019 Aug 27.
• [41] Osmotic Induction of Angiogenic Growth Factor Expression in Human Retinal Pigment Epithelial Cells. PLoS One. 2016 Jan 22;11(1):e0147312. doi: 10.1371/journal.pone.0147312. eCollection 2016.
• [42] Ammonia promotes endothelial cell survival via the heme oxygenase-1-mediated release of carbon monoxide. Free Radic Biol Med. 2017 Jan;102:37-46. doi: 10.1016/j.freeradbiomed.2016.11.029. Epub 2016 Nov 17.
• [43] Profiling the immunotoxicity of chemicals based on in vitro evaluation by a combination of the Multi-ImmunoTox assay and the IL-8 Luc assay. Arch Toxicol. 2018 Jun;92(6):2043-2054. doi: 10.1007/s00204-018-2199-7. Epub 2018 Mar 29.
• [44] Actinomycin D upregulates proapoptotic protein Puma and downregulates Bcl-2 mRNA in normal peripheral blood lymphocytes. Anticancer Drugs. 2007 Aug;18(7):763-72. doi: 10.1097/CAD.0b013e3280adc905.
• [45] Enhanced GRP78 protein expression via the IRE1/ASK1/p38 MAPK pathway during As(2)O(3)-induced endoplasmic reticulum stress in BEAS-2B cells. Toxicology. 2021 Oct;462:152962. doi: 10.1016/j.tox.2021.152962. Epub 2021 Sep 21.
• [46] Matrix metalloproteinase-9 is involved in chronic lymphocytic leukemia cell response to fludarabine and arsenic trioxide. PLoS One. 2014 Jun 23;9(6):e99993. doi: 10.1371/journal.pone.0099993. eCollection 2014.
• [47] Specific inhibition of rRNA transcription and dynamic relocation of fibrillarin induced by mercury. Exp Cell Res. 2000 Aug 25;259(1):225-38. doi: 10.1006/excr.2000.4923.
• [48] Phosphorylation of the RNA polymerase II largest subunit during heat shock and inhibition of transcription in HeLa cells. J Cell Physiol. 1994 Mar;158(3):417-26. doi: 10.1002/jcp.1041580305.
• [49] Selective and nonselective toxicity of TRAIL/Apo2L combined with chemotherapy in human bone tumour cells vs. normal human cells. Int J Cancer. 2003 Dec 20;107(6):929-40. doi: 10.1002/ijc.11503.
• [50] Actinomycin D and staurosporine, potent apoptosis inducers in vitro, are potentially effective chemotherapeutic agents against glioblastoma multiforme. Cancer Chemother Pharmacol. 2000;45(2):149-56. doi: 10.1007/s002800050023.
• [51] Unpredicted Downregulation of RAD51 Suggests Genome Instability Induced by Tetrachlorobenzoquinone. Chem Res Toxicol. 2016 Dec 19;29(12):2184-2193. doi: 10.1021/acs.chemrestox.6b00369. Epub 2016 Nov 21.
• [52] Mechanisms of thymidine kinase/ganciclovir and cytosine deaminase/ 5-fluorocytosine suicide gene therapy-induced cell death in glioma cells. Oncogene. 2005 Feb 10;24(7):1231-43. doi: 10.1038/sj.onc.1208290.
• [53] Quercetin downregulates Mcl-1 by acting on mRNA stability and protein degradation. Br J Cancer. 2011 Jul 12;105(2):221-30. doi: 10.1038/bjc.2011.229.
• [54] Androgen receptor-dependent transactivation of growth arrest-specific gene 6 mediates inhibitory effects of testosterone on vascular calcification. J Biol Chem. 2010 Mar 5;285(10):7537-44. doi: 10.1074/jbc.M109.055087. Epub 2010 Jan 4.
• [55] A high-throughput screen for teratogens using human pluripotent stem cells. Toxicol Sci. 2014 Jan;137(1):76-90. doi: 10.1093/toxsci/kft239. Epub 2013 Oct 23.
• [56] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [57] [Expression of C1QBP gene and its correlation with drug resistance in human resistance choriocarcinoma cell line]. Zhonghua Fu Chan Ke Za Zhi. 2014 Aug;49(8):616-20.
• [58] Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
• [59] Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.Hum Genet. 2018 Apr;137(4):293-303. doi: 10.1007/s00439-018-1882-3. Epub 2018 Apr 24.