Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation.
3-aminobenzamide
Chronic myeloid leukemia
Immunogenic cell death
Indolequinone
NAD
Necrosis
OXPHOS
PARP1
Journal
Biomarker research
ISSN: 2050-7771
Titre abrégé: Biomark Res
Pays: England
ID NLM: 101607860
Informations de publication
Date de publication:
04 May 2024
04 May 2024
Historique:
received:
24
04
2024
accepted:
27
04
2024
medline:
5
5
2024
pubmed:
5
5
2024
entrez:
4
5
2024
Statut:
epublish
Résumé
Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence. Transcriptomic analysis was conducted using datasets of CML patients' stem cells and healthy cells. DNA damage was evaluated by fluorescent microscopy and flow cytometry. Cell death was assessed by trypan blue exclusion test, fluorescent microscopy, flow cytometry, colony formation assay, and in vivo Zebrafish xenografts. Energy metabolism was determined by measuring NAD Transcriptomic analysis identified metabolic alterations and DNA repair deficiency signatures in CML patients. CML patients exhibited enrichment in immune system, DNA repair, and metabolic pathways. The gene signature associated with BRCA mutated tumors was enriched in CML datasets, suggesting a deficiency in double-strand break repair pathways. Additionally, poly(ADP-ribose) polymerase (PARP)1 was significantly upregulated in CML patients' stem cells compared to healthy counterparts. Consistent with the CML patient DNA repair signature, treatment with the methylated indolequinone MAC681 induced DNA damage, mitochondrial dysfunction, calcium homeostasis disruption, metabolic catastrophe, and necroptotic-like cell death. In parallel, MAC681 led to PARP1 degradation that was prevented by 3-aminobenzamide. MAC681-treated myeloid leukemia cells released DAMPs and demonstrated the potential to generate an immunogenic vaccine in C57BL/6 mice. MAC681 and asciminib exhibited synergistic effects in killing both imatinib-sensitive and -resistant CML, opening new therapeutic opportunities. Overall, increasing the tumor mutational burden by PARP1 degradation and mitochondrial deregulation makes CML suitable for immunotherapy.
Sections du résumé
BACKGROUND
BACKGROUND
Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence.
METHODS
METHODS
Transcriptomic analysis was conducted using datasets of CML patients' stem cells and healthy cells. DNA damage was evaluated by fluorescent microscopy and flow cytometry. Cell death was assessed by trypan blue exclusion test, fluorescent microscopy, flow cytometry, colony formation assay, and in vivo Zebrafish xenografts. Energy metabolism was determined by measuring NAD
RESULTS
RESULTS
Transcriptomic analysis identified metabolic alterations and DNA repair deficiency signatures in CML patients. CML patients exhibited enrichment in immune system, DNA repair, and metabolic pathways. The gene signature associated with BRCA mutated tumors was enriched in CML datasets, suggesting a deficiency in double-strand break repair pathways. Additionally, poly(ADP-ribose) polymerase (PARP)1 was significantly upregulated in CML patients' stem cells compared to healthy counterparts. Consistent with the CML patient DNA repair signature, treatment with the methylated indolequinone MAC681 induced DNA damage, mitochondrial dysfunction, calcium homeostasis disruption, metabolic catastrophe, and necroptotic-like cell death. In parallel, MAC681 led to PARP1 degradation that was prevented by 3-aminobenzamide. MAC681-treated myeloid leukemia cells released DAMPs and demonstrated the potential to generate an immunogenic vaccine in C57BL/6 mice. MAC681 and asciminib exhibited synergistic effects in killing both imatinib-sensitive and -resistant CML, opening new therapeutic opportunities.
CONCLUSIONS
CONCLUSIONS
Overall, increasing the tumor mutational burden by PARP1 degradation and mitochondrial deregulation makes CML suitable for immunotherapy.
Identifiants
pubmed: 38704604
doi: 10.1186/s40364-024-00594-w
pii: 10.1186/s40364-024-00594-w
doi:
Types de publication
Journal Article
Langues
eng
Pagination
47Informations de copyright
© 2024. The Author(s).
Références
Cortes JE, Jones D, O’Brien S, Jabbour E, Ravandi F, Koller C, et al. Results of dasatinib therapy in patients with early chronic-phase chronic myeloid leukemia. J Clin Oncol. 2010;28(3):398–404.
pubmed: 20008620
doi: 10.1200/JCO.2009.25.4920
Kantarjian HM, Shah NP, Cortes JE, Baccarani M, Agarwal MB, Undurraga MS, et al. Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION). Blood. 2012;119(5):1123–9.
pubmed: 22160483
pmcid: 4916556
doi: 10.1182/blood-2011-08-376087
Zulbaran-Rojas A, Lin HK, Shi Q, Williams LA, George B, Garcia-Manero G, et al. A prospective analysis of symptom burden for patients with chronic myeloid leukemia in chronic phase treated with frontline second- and third-generation tyrosine kinase inhibitors. Cancer Med. 2018;7(11):5457–69.
pubmed: 30318751
pmcid: 6246941
doi: 10.1002/cam4.1808
Rossari F, Minutolo F, Orciuolo E. Past, present, and future of Bcr-Abl inhibitors: from chemical development to clinical efficacy. J Hematol Oncol. 2018;11(1):84.
pubmed: 29925402
pmcid: 6011351
doi: 10.1186/s13045-018-0624-2
Kuntz EM, Baquero P, Michie AM, Dunn K, Tardito S, Holyoake TL, et al. Targeting mitochondrial oxidative phosphorylation eradicates therapy-resistant chronic myeloid leukemia stem cells. Nat Med. 2017;23(10):1234–40.
pubmed: 28920959
pmcid: 5657469
doi: 10.1038/nm.4399
Simsek T, Kocabas F, Zheng J, Deberardinis RJ, Mahmoud AI, Olson EN, et al. The distinct metabolic profile of hematopoietic stem cells reflects their location in a hypoxic niche. Cell Stem Cell. 2010;7(3):380–90.
pubmed: 20804973
pmcid: 4159713
doi: 10.1016/j.stem.2010.07.011
Mojtahedi H, Yazdanpanah N, Rezaei N. Chronic myeloid leukemia stem cells: targeting therapeutic implications. Stem Cell Res Ther. 2021;12(1):603.
pubmed: 34922630
pmcid: 8684082
doi: 10.1186/s13287-021-02659-1
de Beauchamp L, Himonas E, Helgason GV. Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia. Leukemia. 2022;36(1):1–12.
pubmed: 34561557
doi: 10.1038/s41375-021-01416-w
Liu L, Su X, Quinn WJ 3rd, Hui S, Krukenberg K, Frederick DW, et al. Quantitative analysis of NAD synthesis-breakdown fluxes. Cell Metab. 2018;27(5):1067-80 e5.
pubmed: 29685734
pmcid: 5932087
doi: 10.1016/j.cmet.2018.03.018
Xie N, Zhang L, Gao W, Huang C, Huber PE, Zhou X, et al. NAD(+) metabolism: pathophysiologic mechanisms and therapeutic potential. Signal Transduct Target Ther. 2020;5(1):227.
pubmed: 33028824
pmcid: 7539288
doi: 10.1038/s41392-020-00311-7
Muvarak N, Nagaria P, Rassool FV. Genomic instability in chronic myeloid leukemia: targets for therapy? Curr Hematol Malig Rep. 2012;7(2):94–102.
pubmed: 22427031
doi: 10.1007/s11899-012-0119-0
Sallmyr A, Tomkinson AE, Rassool FV. Up-regulation of WRN and DNA ligase IIIalpha in chronic myeloid leukemia: consequences for the repair of DNA double-strand breaks. Blood. 2008;112(4):1413–23.
pubmed: 18524993
pmcid: 2967309
doi: 10.1182/blood-2007-07-104257
Tobin LA, Robert C, Rapoport AP, Gojo I, Baer MR, Tomkinson AE, Rassool FV. Targeting abnormal DNA double-strand break repair in tyrosine kinase inhibitor-resistant chronic myeloid leukemias. Oncogene. 2013;32(14):1784–93.
pubmed: 22641215
doi: 10.1038/onc.2012.203
Bolton-Gillespie E, Schemionek M, Klein HU, Flis S, Hoser G, Lange T, et al. Genomic instability may originate from imatinib-refractory chronic myeloid leukemia stem cells. Blood. 2013;121(20):4175–83.
pubmed: 23543457
pmcid: 3656452
doi: 10.1182/blood-2012-11-466938
Ross D, Siegel D, Beall H, Prakash AS, Mulcahy RT, Gibson NW. DT-diaphorase in activation and detoxification of quinones. Bioreductive activation of mitomycin C. Cancer Metastasis Rev. 1993;12(2):83–101.
pubmed: 8375023
doi: 10.1007/BF00689803
Reigan P, Colucci MA, Siegel D, Chilloux A, Moody CJ, Ross D. Development of indolequinone mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1): NQO1 inhibition and growth inhibitory activity in human pancreatic MIA PaCa-2 cancer cells. Biochemistry. 2007;46(20):5941–50.
pubmed: 17455910
doi: 10.1021/bi700008y
Colucci MA, Reigan P, Siegel D, Chilloux A, Ross D, Moody CJ. Synthesis and evaluation of 3-aryloxymethyl-1,2-dimethylindole-4,7-diones as mechanism-based inhibitors of NAD(P)H:quinone oxidoreductase 1 (NQO1) activity. J Med Chem. 2007;50(23):5780–9.
pubmed: 17944451
pmcid: 2536657
doi: 10.1021/jm070396q
Qin R, You FM, Zhao Q, Xie X, Peng C, Zhan G, Han B. Naturally derived indole alkaloids targeting regulated cell death (RCD) for cancer therapy: from molecular mechanisms to potential therapeutic targets. J Hematol Oncol. 2022;15(1):133.
pubmed: 36104717
pmcid: 9471064
doi: 10.1186/s13045-022-01350-z
Krysko O, Aaes TL, Kagan VE, D’Herde K, Bachert C, Leybaert L, et al. Necroptotic cell death in anti-cancer therapy. Immunol Rev. 2017;280(1):207–19.
pubmed: 29027225
doi: 10.1111/imr.12583
Hernandez AP, Juanes-Velasco P, Landeira-Vinuela A, Bareke H, Montalvillo E, Gongora R, Fuentes M. Restoring the immunity in the tumor microenvironment: insights into immunogenic cell death in onco-therapies. Cancers (Basel). 2021;13(11):2821.
pubmed: 34198850
doi: 10.3390/cancers13112821
Galluzzi L, Vacchelli E, Bravo-San Pedro JM, Buque A, Senovilla L, Baracco EE, et al. Classification of current anticancer immunotherapies. Oncotarget. 2014;5(24):12472–508.
pubmed: 25537519
pmcid: 4350348
doi: 10.18632/oncotarget.2998
Diaz-Blanco E, Bruns I, Neumann F, Fischer JC, Graef T, Rosskopf M, et al. Molecular signature of CD34(+) hematopoietic stem and progenitor cells of patients with CML in chronic phase. Leukemia. 2007;21(3):494–504.
pubmed: 17252012
doi: 10.1038/sj.leu.2404549
Gautier L, Cope L, Bolstad BM, Irizarry RA. affy–analysis of Affymetrix GeneChip data at the probe level. Bioinformatics. 2004;20(3):307–15.
pubmed: 14960456
doi: 10.1093/bioinformatics/btg405
Aviles-Vazquez S, Chavez-Gonzalez A, Hidalgo-Miranda A, Moreno-Lorenzana D, Arriaga-Pizano L, Sandoval-Esquivel MA, et al. Global gene expression profiles of hematopoietic stem and progenitor cells from patients with chronic myeloid leukemia: the effect of in vitro culture with or without imatinib. Cancer Med. 2017;6(12):2942–56.
pubmed: 29030909
pmcid: 5727298
doi: 10.1002/cam4.1187
Abraham SA, Hopcroft LE, Carrick E, Drotar ME, Dunn K, Williamson AJ, et al. Dual targeting of p53 and c-MYC selectively eliminates leukaemic stem cells. Nature. 2016;534(7607):341–6.
pubmed: 27281222
pmcid: 4913876
doi: 10.1038/nature18288
Parker HS, Corrada Bravo H, Leek JT. Removing batch effects for prediction problems with frozen surrogate variable analysis. PeerJ. 2014;2:e561.
pubmed: 25332844
pmcid: 4179553
doi: 10.7717/peerj.561
Kohlmann A, Kipps TJ, Rassenti LZ, Downing JR, Shurtleff SA, Mills KI, et al. An international standardization programme towards the application of gene expression profiling in routine leukaemia diagnostics: the microarray Innovations in LEukemia study prephase. Br J Haematol. 2008;142(5):802–7.
pubmed: 18573112
pmcid: 2654477
doi: 10.1111/j.1365-2141.2008.07261.x
Ghandi M, Huang FW, Jane-Valbuena J, Kryukov GV, Lo CC, McDonald ER 3rd, et al. Next-generation characterization of the cancer cell line encyclopedia. Nature. 2019;569(7757):503–8.
pubmed: 31068700
pmcid: 6697103
doi: 10.1038/s41586-019-1186-3
Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W, Smyth GK. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015;43(7): e47.
pubmed: 25605792
pmcid: 4402510
doi: 10.1093/nar/gkv007
Wickham H. Build a Plot Layer by Layer. In: Wickham H, editor. ggplot2. Use R! Cham: Springer International Publishing; 2016. p. 89–107.
doi: 10.1007/978-3-319-24277-4_5
Gillespie M, Jassal B, Stephan R, Milacic M, Rothfels K, Senff-Ribeiro A, et al. The reactome pathway knowledgebase 2022. Nucleic Acids Res. 2022;50(D1):D687–92.
pubmed: 34788843
doi: 10.1093/nar/gkab1028
Orlikova B, Tasdemir D, Golais F, Dicato M, Diederich M. The aromatic ketone 4’-hydroxychalcone inhibits TNFalpha-induced NF-kappaB activation via proteasome inhibition. Biochem Pharmacol. 2011;82(6):620–31.
pubmed: 21703248
doi: 10.1016/j.bcp.2011.06.012
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–5.
pubmed: 22930834
pmcid: 5554542
doi: 10.1038/nmeth.2089
Yan JS, Yang MY, Zhang XH, Luo CH, Du CK, Jiang Y, et al. Mitochondrial oxidative phosphorylation is dispensable for survival of CD34(+) chronic myeloid leukemia stem and progenitor cells. Cell Death Dis. 2022;13(4):384.
pubmed: 35444236
pmcid: 9021200
doi: 10.1038/s41419-022-04842-5
Pujana MA, Han JD, Starita LM, Stevens KN, Tewari M, Ahn JS, et al. Network modeling links breast cancer susceptibility and centrosome dysfunction. Nat Genet. 2007;39(11):1338–49.
pubmed: 17922014
doi: 10.1038/ng.2007.2
O’Sullivan CC, Moon DH, Kohn EC, Lee JM. Beyond breast and ovarian cancers: PARP Inhibitors for BRCA mutation-associated and BRCA-like solid tumors. Front Oncol. 2014;4:42.
pubmed: 24616882
pmcid: 3937815
Paulet L, Trecourt A, Leary A, Peron J, Descotes F, Devouassoux-Shisheboran M, et al. Cracking the homologous recombination deficiency code: how to identify responders to PARP inhibitors. Eur J Cancer. 2022;166:87–99.
pubmed: 35279473
doi: 10.1016/j.ejca.2022.01.037
Kamel D, Gray C, Walia JS, Kumar V. PARP inhibitor drugs in the treatment of breast, ovarian, prostate and pancreatic cancers: an update of clinical trials. Curr Drug Targets. 2018;19(1):21–37.
pubmed: 28699513
doi: 10.2174/1389450118666170711151518
listed Na. AZD5305 more tolerable than earlier PARP Agents. Cancer Discov. 2022;12(7):1602.
doi: 10.1158/2159-8290.CD-NB2022-0039
Bai P, Nagy L, Fodor T, Liaudet L, Pacher P. Poly(ADP-ribose) polymerases as modulators of mitochondrial activity. Trends Endocrinol Metab. 2015;26(2):75–83.
pubmed: 25497347
doi: 10.1016/j.tem.2014.11.003
Fouquerel E, Sobol RW. ARTD1 (PARP1) activation and NAD(+) in DNA repair and cell death. DNA Repair (Amst). 2014;23:27–32.
pubmed: 25283336
doi: 10.1016/j.dnarep.2014.09.004
Rasola A, Bernardi P. Mitochondrial permeability transition in Ca(2+)-dependent apoptosis and necrosis. Cell Calcium. 2011;50(3):222–33.
pubmed: 21601280
doi: 10.1016/j.ceca.2011.04.007
Vosler PS, Sun D, Wang S, Gao Y, Kintner DB, Signore AP, et al. Calcium dysregulation induces apoptosis-inducing factor release: cross-talk between PARP-1- and calpain-signaling pathways. Exp Neurol. 2009;218(2):213–20.
pubmed: 19427306
pmcid: 2710414
doi: 10.1016/j.expneurol.2009.04.032
Lernoux M, Schnekenburger M, Losson H, Vermeulen K, Hahn H, Gerard D, et al. Novel HDAC inhibitor MAKV-8 and imatinib synergistically kill chronic myeloid leukemia cells via inhibition of BCR-ABL/MYC-signaling: effect on imatinib resistance and stem cells. Clin Epigenetics. 2020;12(1):69.
pubmed: 32430012
pmcid: 7236970
doi: 10.1186/s13148-020-00839-z
Losson H, Gajulapalli SR, Lernoux M, Lee JY, Mazumder A, Gerard D, et al. The HDAC6 inhibitor 7b induces BCR-ABL ubiquitination and downregulation and synergizes with imatinib to trigger apoptosis in chronic myeloid leukemia. Pharmacol Res. 2020;160:105058.
pubmed: 32619722
doi: 10.1016/j.phrs.2020.105058
Yan C, Shieh B, Reigan P, Zhang Z, Colucci MA, Chilloux A, et al. Potent activity of indolequinones against human pancreatic cancer: identification of thioredoxin reductase as a potential target. Mol Pharmacol. 2009;76(1):163–72.
pubmed: 19364812
pmcid: 2701460
doi: 10.1124/mol.109.055855
He M, Sheldon PJ, Sherman DH. Characterization of a quinone reductase activity for the mitomycin C binding protein (MRD): Functional switching from a drug-activating enzyme to a drug-binding protein. Proc Natl Acad Sci U S A. 2001;98(3):926–31.
pubmed: 11158572
pmcid: 14686
doi: 10.1073/pnas.98.3.926
Sukkurwala AQ, Martins I, Wang Y, Schlemmer F, Ruckenstuhl C, Durchschlag M, et al. Immunogenic calreticulin exposure occurs through a phylogenetically conserved stress pathway involving the chemokine CXCL8. Cell Death Differ. 2014;21(1):59–68.
pubmed: 23787997
doi: 10.1038/cdd.2013.73
Kepp O, Senovilla L, Kroemer G. Immunogenic cell death inducers as anticancer agents. Oncotarget. 2014;5(14):5190–1.
pubmed: 25114034
pmcid: 4170601
doi: 10.18632/oncotarget.2266
Jin S, DiPaola RS, Mathew R, White E. Metabolic catastrophe as a means to cancer cell death. J Cell Sci. 2007;120(Pt 3):379–83.
pubmed: 17251378
doi: 10.1242/jcs.03349
Song S, Lee JY, Ermolenko L, Mazumder A, Ji S, Ryu H, et al. Tetrahydrobenzimidazole TMQ0153 triggers apoptosis, autophagy and necroptosis crosstalk in chronic myeloid leukemia. Cell Death Dis. 2020;11(2):109.
pubmed: 32034134
pmcid: 7007439
doi: 10.1038/s41419-020-2304-8
Patel SB, Nemkov T, Stefanoni D, Benavides GA, Bassal MA, Crown BL, et al. Metabolic alterations mediated by STAT3 promotes drug persistence in CML. Leukemia. 2021;35(12):3371–82.
pubmed: 34120146
pmcid: 8632690
doi: 10.1038/s41375-021-01315-0
Li Y, Zeng P, Xiao J, Huang P, Liu P. Modulation of energy metabolism to overcome drug resistance in chronic myeloid leukemia cells through induction of autophagy. Cell Death Discov. 2022;8(1):212.
pubmed: 35443725
pmcid: 9021256
doi: 10.1038/s41420-022-00991-w
Gottschalk S, Anderson N, Hainz C, Eckhardt SG, Serkova NJ. Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin Cancer Res. 2004;10(19):6661–8.
pubmed: 15475456
doi: 10.1158/1078-0432.CCR-04-0039
De Rosa V, Monti M, Terlizzi C, Fonti R, Del Vecchio S, Iommelli F. Coordinate modulation of glycolytic enzymes and OXPHOS by Imatinib in BCR-ABL driven chronic myelogenous leukemia cells. Int J Mol Sci. 2019;20(13):3134.
pubmed: 31252559
pmcid: 6651622
doi: 10.3390/ijms20133134
Karlikova R, Siroka J, Friedecky D, Faber E, Hrda M, Micova K, et al. Metabolite profiling of the plasma and leukocytes of chronic myeloid leukemia patients. J Proteome Res. 2016;15(9):3158–66.
pubmed: 27465658
doi: 10.1021/acs.jproteome.6b00356
Kluza J, Jendoubi M, Ballot C, Dammak A, Jonneaux A, Idziorek T, et al. Exploiting mitochondrial dysfunction for effective elimination of imatinib-resistant leukemic cells. PLoS ONE. 2011;6(7):e21924.
pubmed: 21789194
pmcid: 3138741
doi: 10.1371/journal.pone.0021924
Pawlowska E, Blasiak J. DNA repair–a double-edged sword in the genomic stability of cancer cells-the case of chronic myeloid leukemia. Int J Mol Sci. 2015;16(11):27535–49.
pubmed: 26593906
pmcid: 4661907
doi: 10.3390/ijms161126049
Benito R, Lumbreras E, Abaigar M, Gutierrez NC, Delgado M, Robledo C, et al. Imatinib therapy of chronic myeloid leukemia restores the expression levels of key genes for DNA damage and cell-cycle progression. Pharmacogenet Genomics. 2012;22(5):381–8.
pubmed: 22388797
doi: 10.1097/FPC.0b013e328351f3e9
G. Lindström HJ, Friedman R. The effects of combination treatments on drug resistance in chronic myeloid leukaemia: an evaluation of the tyrosine kinase inhibitors axitinib and asciminib. BMC Cancer. 2020;20(1):397.
pubmed: 32380976
pmcid: 7204252
doi: 10.1186/s12885-020-06782-9
Haselbarth L, Karow A, Mentz K, Bottcher M, Roche-Lancaster O, Krumbholz M, et al. Effects of the STAMP-inhibitor asciminib on T cell activation and metabolic fitness compared to tyrosine kinase inhibition by imatinib, dasatinib, and nilotinib. Cancer Immunol Immunother. 2023;72(6):1661–72.
pubmed: 36602564
pmcid: 10198838
doi: 10.1007/s00262-022-03361-8
Andrabi SA, Dawson TM, Dawson VL. Mitochondrial and nuclear cross talk in cell death: parthanatos. Ann N Y Acad Sci. 2008;1147(1):233–41.
pubmed: 19076445
pmcid: 4454457
doi: 10.1196/annals.1427.014
Somers K, Wen VW, Middlemiss SMC, Osborne B, Forgham H, Jung M, et al. A novel small molecule that kills a subset of MLL-rearranged leukemia cells by inducing mitochondrial dysfunction. Oncogene. 2019;38(20):3824–42.
pubmed: 30670779
pmcid: 6756102
doi: 10.1038/s41388-018-0666-5
Seo KS, Kim JH, Min KN, Moon JA, Roh TC, Lee MJ, et al. KL1333, a Novel NAD(+) modulator, improves energy metabolism and mitochondrial dysfunction in MELAS fibroblasts. Front Neurol. 2018;9:552.
pubmed: 30026729
pmcid: 6041391
doi: 10.3389/fneur.2018.00552
Moore Z, Chakrabarti G, Luo X, Ali A, Hu Z, Fattah FJ, et al. NAMPT inhibition sensitizes pancreatic adenocarcinoma cells to tumor-selective, PAR-independent metabolic catastrophe and cell death induced by beta-lapachone. Cell Death Dis. 2015;6(1):e1599.
pubmed: 25590809
pmcid: 4669762
doi: 10.1038/cddis.2014.564
Zhong B, Yu J, Hou Y, Ai N, Ge W, Lu JJ, Chen X. A novel strategy for glioblastoma treatment by induction of noptosis, an NQO1-dependent necrosis. Free Radic Biol Med. 2021;166:104–15.
pubmed: 33600944
doi: 10.1016/j.freeradbiomed.2021.02.014
Kelland LR, Tonkin KS. The effect of 3-aminobenzamide in the radiation response of three human cervix carcinoma xenografts. Radiother Oncol. 1989;15(4):363–9.
pubmed: 2508193
doi: 10.1016/0167-8140(89)90083-2
Dubner D, del Rosario PM, Michelin S, Bourguignon M, Moreau P, Carosella ED, Gisone P. Pharmacological inhibition of DNA repair enzymes differentially modulates telomerase activity and apoptosis in two human leukaemia cell lines. Int J Radiat Biol. 2004;80(8):593–605.
pubmed: 15370971
doi: 10.1080/09553000412331283506
Wang H, Lu C, Li Q, Xie J, Chen T, Tan Y, et al. The role of Kif4A in doxorubicin-induced apoptosis in breast cancer cells. Mol Cells. 2014;37(11):812–8.
pubmed: 25377255
pmcid: 4255101
doi: 10.14348/molcells.2014.0210
Wang H, Lu C, Tan Y, Xie J, Jiang J. Effect of adriamycin on BRCA1 and PARP-1 expression in MCF-7 breast cancer cells. Int J Clin Exp Pathol. 2014;7(9):5909–15.
pubmed: 25337234
pmcid: 4203205
Nguewa PA, Fuertes MA, Cepeda V, Alonso C, Quevedo C, Soto M, Perez JM. Poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide enhances apoptosis induction by platinum complexes in cisplatin-resistant tumor cells. Med Chem. 2006;2(1):47–53.
pubmed: 16787355
doi: 10.2174/157340606775197697
Jacob DA, Bahra M, Langrehr JM, Boas-Knoop S, Stefaniak R, Davis J, et al. Combination therapy of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide and gemcitabine shows strong antitumor activity in pancreatic cancer cells. J Gastroenterol Hepatol. 2007;22(5):738–48.
pubmed: 17444865
doi: 10.1111/j.1440-1746.2006.04496.x
Keppler BD, Song J, Nyman J, Voigt CA, Bent AF. 3-Aminobenzamide Blocks MAMP-induced callose deposition independently of its poly(ADPribosyl)ation inhibiting activity. Front Plant Sci. 2018;9:1907.
pubmed: 30619442
pmcid: 6305757
doi: 10.3389/fpls.2018.01907
Ricciarelli R, Palomba L, Cantoni O, Azzi A. 3-Aminobenzamide inhibition of protein kinase C at a cellular level. FEBS Lett. 1998;431(3):465–7.
pubmed: 9714565
doi: 10.1016/S0014-5793(98)00811-4
Czapski GA, Cakala M, Kopczuk D, Strosznajder JB. Effect of poly(ADP-ribose) polymerase inhibitors on oxidative stress evoked hydroxyl radical level and macromolecules oxidation in cell free system of rat brain cortex. Neurosci Lett. 2004;356(1):45–8.
pubmed: 14746898
doi: 10.1016/j.neulet.2003.11.022
Eriksson C, Busk L, Brittebo EB. 3-Aminobenzamide: effects on cytochrome P450-dependent metabolism of chemicals and on the toxicity of dichlobenil in the olfactory mucosa. Toxicol Appl Pharmacol. 1996;136(2):324–31.
pubmed: 8619240
doi: 10.1006/taap.1996.0039
Dela Cruz CS, Kang MJ. Mitochondrial dysfunction and damage associated molecular patterns (DAMPs) in chronic inflammatory diseases. Mitochondrion. 2018;41:37–44.
pubmed: 29221810
doi: 10.1016/j.mito.2017.12.001