134
Views
4
CrossRef citations to date
0
Altmetric
Perspectives

Targeting Protein Neddylation to Inactivate Cullin-RING Ligases by Gossypol: A Lucky Hit or a New Start?

ORCID Icon &
Pages 1-8 | Published online: 06 Jan 2021

References

  • CollinsGA, GoldbergAL. The logic of the 26S proteasome. Cell. 2017;169(5):792–806. doi:10.1016/j.cell.2017.04.02328525752
  • HershkoA, CiechanoverA. The ubiquitin system. Annu Rev Biochem. 1998;67:425–479. doi:10.1146/annurev.biochem.67.1.4259759494
  • YeY, RapeM. Building ubiquitin chains: E2 enzymes at work. Nat Rev Mol Cell Biol. 2009;10:755–764. doi:10.1038/nrm278019851334
  • SchulmanBA, Wade HarperJ, HarperJW. Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nat Rev Mol Cell Biol. 2009;10:319–331. doi:10.1038/nrm267319352404
  • DeshaiesRJ, JoazeiroCAP. RING domain E3 ubiquitin ligases. Annu Rev Biochem. 2009;78:399–434. doi:10.1146/annurev.biochem.78.101807.09380919489725
  • ZhengN, ShabekN. Ubiquitin ligases: structure, function, and regulation. Annu Rev Biochem. 2017;86:129–157. doi:10.1146/annurev-biochem-060815-01492228375744
  • SoucyTA, SmithPG, MilhollenMA, et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature. 2009;458:732–736. doi:10.1038/nature0788419360080
  • Introduction. Advances in experimental medicine and biology; 2020.
  • ZhouL, ZhangW, SunY, JiaL. Protein neddylation and its alterations in human cancers for targeted therapy. Cell Signal. 2018;44:92–102. doi:10.1016/j.cellsig.2018.01.00929331584
  • YuQ, JiangY, SunY. Anticancer drug discovery by targeting cullin neddylation. Acta Pharm Sin B. 2020;10(5):746–765. doi:10.1016/j.apsb.2019.09.00532528826
  • YuQ, HuZ, ShenY, et al. Gossypol inhibits cullin neddylation by targeting SAG-CUL5 and RBX1-CUL1 complexes. Neoplasia. 2020;22(4):179–191. doi:10.1016/j.neo.2020.02.00332145688
  • GoldbergAL. Development of proteasome inhibitors as research tools and cancer drugs. J Cell Biol. 2012;199(4):583–588. doi:10.1083/jcb.20121007723148232
  • RaabMS, PodarK, BreitkreutzI, RichardsonPG, AndersonKC. Multiple myeloma. Lancet. 2009;374(9686):324–339. doi:10.1016/S0140-6736(09)60221-X19541364
  • MikhaelJ, IsmailaN, CheungMC, et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol. 2019;37(14):1228–1263. doi:10.1200/JCO.18.0209630932732
  • ParkJE, MillerZ, JunY, LeeW, KimKB. Next-generation proteasome inhibitors for cancer therapy. Transl Res. 2018;198:1–16. doi:10.1016/j.trsl.2018.03.00229654740
  • ManasanchEE, OrlowskiRZ. Proteasome inhibitors in cancer therapy. Nat Rev Clin Oncol. 2017;14(7):417–433. doi:10.1038/nrclinonc.2016.20628117417
  • BulatovE, ValiullinaA, SayarovaR, RizvanovA. Promising new therapeutic targets for regulation of inflammation and immunity: RING-type E3 ubiquitin ligases. Immunol Lett. 2018;202:44–51. doi:10.1016/j.imlet.2018.08.00130099009
  • CrawfordDR, AmstadPA, FooDD, CeruttiPA. Constitutive and phorbol-myristate-acetate regulated antioxidant defense of mouse epidermal JB6 cells. Mol Carcinog. 1989;2(3):136–143.2789690
  • ZhaoY, MorganMA, SunY. Targeting neddylation pathways to inactivate Cullin-RING ligases for anti-cancer therapy. Antioxid Redox Signal. 2014;21(17):2383–2400. doi:10.1089/ars.2013.579524410571
  • FergusonFM, GrayNS. Kinase inhibitors: the road ahead. Nat Rev Drug Discov. 2018;17:353–376.29545548
  • ShengC, DongG, MiaoZ, ZhangW, WangW. State-of-the-art strategies for targeting protein-protein interactions by small-molecule inhibitors. Chem Soc Rev. 2015;44:8238–8259. doi:10.1039/C5CS00252D26248294
  • BlundellTL, BurkeDF, ChirgadzeD, et al. Protein-protein interactions in receptor activation and intracellular signalling. Biol Chem. 2000;381:955–959. doi:10.1515/BC.2000.11711076027
  • BaekK, KristDT, PrabuJR, et al. NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly. Nature. 2020;578(7795):461–466. doi:10.1038/s41586-020-2000-y32051583
  • WuK, ChongRA, YuQ, et al. Suramin inhibits cullin-RING E3 ubiquitin ligases. Proc Natl Acad Sci. 2016;113(14):E2011–E2018. doi:10.1073/pnas.160108911327001857
  • CeccarelliDF, TangX, PelletierB, et al. An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme. Cell. 2011;145(7):1075–1087. doi:10.1016/j.cell.2011.05.03921683433
  • QianSZ, WangZG. Gossypol: a potential antifertility agent for males. Annu Rev Pharmacol Toxicol. 1984;24:329–360. doi:10.1146/annurev.pa.24.040184.0015536375548
  • BenvenutoM, MatteraR, SticcaJI, et al. Effect of the BH3 mimetic polyphenol (-)-Gossypol (AT-101) on the in vitro and in vivo growth of malignant mesothelioma. Front Pharmacol. 2018;9:1269. doi:10.3389/fphar.2018.0126930459622
  • Keshmiri-NeghabH, GoliaeiB. Therapeutic potential of gossypol: an overview. Pharm Biol. 2014;52(1):124–128. doi:10.3109/13880209.2013.83277624073600
  • KitadaS, LeoneM, SarethS, ZhaiD, ReedJC, PellecchiaM. Discovery, characterization, and structure-activity relationships studies of proapoptotic polyphenols targeting B-cell lymphocyte/leukemia-2 proteins. J Med Chem. 2003;46(20):4259–4264. doi:10.1021/jm030190z13678404
  • VoglerM. Targeting BCL2-proteins for the treatment of solid tumours. Adv Med. 2014;2014:943648. doi:10.1155/2014/94364826556430
  • WangG, Nikolovska-ColeskaZ, YangC-Y, et al. Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J Med Chem. 2006;49(21):6139–6142. doi:10.1021/jm060460o17034116
  • HanZ, LiangJ, LiY, HeJ. Drugs and clinical approaches targeting the antiapoptotic protein: a review. Biomed Res Int. 2019;2019:1212369. doi:10.1155/2019/121236931662966
  • MehnerM, KubeltC, AdamskiV, SchmittC, SynowitzM, Held-FeindtJ. Combined treatment of AT101 and demethoxycurcumin yields an enhanced anti-proliferative effect in human primary glioblastoma cells. J Cancer Res Clin Oncol. 2020;146(1):117–126. doi:10.1007/s00432-019-03107-731844979
  • SteinMN, GoodinS, GounderM, et al. A Phase I study of AT-101, a BH3 mimetic, in combination with paclitaxel and carboplatin in solid tumors. Invest New Drugs. 2020;38(3):855–865. doi:10.1007/s10637-019-00807-231388792
  • SchelmanWR, MohammedTA, TraynorAM, et al. A phase I study of AT-101 with cisplatin and etoposide in patients with advanced solid tumors with an expanded cohort in extensive-stage small cell lung cancer. Invest New Drugs. 2014;32(2):295–302. doi:10.1007/s10637-013-9999-723860642
  • ReadyN, KarasevaNA, OrlovSV, et al. Double-blind, placebo-controlled, randomized Phase 2 study of the proapoptotic agent AT-101 plus docetaxel, in second-line non-small cell lung cancer. J Thorac Oncol. 2011;6(4):781–785. doi:10.1097/JTO.0b013e31820a0ea621289522
  • Van PoznakC, SeidmanAD, ReidenbergMM, et al. Oral gossypol in the treatment of patients with refractory metastatic breast cancer: a phase I/II clinical trial. Breast Cancer Res Treat. 2001;66:239–248. doi:10.1023/A:101068620473611510695
  • XieH, YinJ, ShahMH, et al. A phase II study of the orally administered negative enantiomer of gossypol (AT-101), a BH3 mimetic, in patients with advanced adrenal cortical carcinoma. Invest New Drugs. 2019;37(4):755–762. doi:10.1007/s10637-019-00797-131172443
  • SteinMN, HussainM, StadlerWM, et al. A Phase II study of AT-101 to overcome Bcl-2-mediated resistance to androgen deprivation therapy in patients with newly diagnosed castration-sensitive metastatic prostate cancer. Clin Genitourin Cancer. 2016;14:22–27. doi:10.1016/j.clgc.2015.09.01026476589
  • SonpavdeG, MatveevV, BurkeJM, et al. Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer. Ann Oncol. 2012;23:1803–1808. doi:10.1093/annonc/mdr55522112969
  • BaggstromMQ, QiY, KoczywasM, et al. A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer. J Thorac Oncol. 2011;6:1757–1760. doi:10.1097/JTO.0b013e31822e294121918390
  • Suk HeistR, FainJ, ChinnasamiB, et al. Phase I/II study of AT-101 with topotecan in relapsed and refractory small cell lung cancer. J Thorac Oncol. 2010;5:1637–1643. doi:10.1097/JTO.0b013e3181e8f4dc20808253
  • LiuG, KellyWK, WildingG, LeopoldL, BrillK, SomerB. An open-label, multicenter, phase I/II study of single-agent AT-101 in men with castrate-resistant prostate cancer. Clin Cancer Res. 2009;15(9):3172–3176. doi:10.1158/1078-0432.CCR-08-298519366825
  • LiguerosM, JeoungD, TangB, HochhauserD, ReidenbergMM, SonenbergM. Gossypol inhibition of mitosis, cyclin D1 and Rb protein in human mammary cancer cells and cyclin-D1 transfected human fibrosarcoma cells. Br J Cancer. 1997;76(1):21–28. doi:10.1038/bjc.1997.3309218727
  • RekhaGK, SladekNE. Inhibition of human class 3 aldehyde dehydrogenase, and sensitization of tumor cells that express significant amounts of this enzyme to oxazaphosphorines, by the naturally occurring compound gossypol. Adv Exp Med Biol. 1997;414:133–146.9059615
  • YangD, QuJ, QuX, et al. Gossypol sensitizes the antitumor activity of 5-FU through down-regulation of thymidylate synthase in human colon carcinoma cells. Cancer Chemother Pharmacol. 2015;76(3):575–586. doi:10.1007/s00280-015-2749-026208739
  • SoderquistRS, DanilovAV, EastmanA. Gossypol increases expression of the pro-apoptotic BH3-only protein NOXA through a novel mechanism involving phospholipase A2, cytoplasmic calcium, and endoplasmic reticulum stress. J Biol Chem. 2014;289(23):16190–16199. doi:10.1074/jbc.M114.56290024778183
  • ZubairH, AzimS, KhanHY, et al. Mobilization of intracellular copper by gossypol and apogossypolone leads to reactive oxygen species-mediated cell death: putative anticancer mechanism. Int J Mol Sci. 2016;17(5):973. doi:10.3390/ijms17060973
  • LuY, LiJ, DongC-E, HuangJ, ZhouH-B, WangW. Recent advances in gossypol derivatives and analogs: a chemistry and biology view. Future Med Chem. 2017;9:1243–1275. doi:10.4155/fmc-2017-004628722469
  • TangG, Nikolovska-ColeskaZ, QiuS, YangC-Y, GuoJ, WangS. Acylpyrogallols as inhibitors of antiapoptotic Bcl-2 proteins. J Med Chem. 2008;51(4):717–720. doi:10.1021/jm701358v18237106
  • YanF, CaoXX, JiangHX, et al. A novel water-soluble gossypol derivative increases chemotherapeutic sensitivity and promotes growth inhibition in colon cancer. J Med Chem. 2010;53:5502–5510. doi:10.1021/jm100169820684596
  • IonovM, GordiyenkoN, OlchowikE, et al. The immobilization of gossypol derivative on N-polyvinylpyrrolidone increases its water solubility and modifies membrane-active properties. J Med Chem. 2009;52:4119–4125. doi:10.1021/jm900250719603832
  • GuikemaJE, AmiotM, ElderingE. Exploiting the pro-apoptotic function of NOXA as a therapeutic modality in cancer. Expert Opin Ther Targets. 2017;21:767–779. doi:10.1080/14728222.2017.134975428670929
  • AlbershardtTC, SalerniBL, SoderquistRS, et al. Multiple BH3 mimetics antagonize antiapoptotic MCL1 protein by inducing the endoplasmic reticulum stress response and up-regulating BH3-only protein NOXA. J Biol Chem. 2011;286:24882–24895. doi:10.1074/jbc.M111.25582821628457
  • MengY, TangW, DaiY, et al. Natural BH3 mimetic (-)-gossypol chemosensitizes human prostate cancer via Bcl-xL inhibition accompanied by increase of Puma and Noxa. Mol Cancer Ther. 2008;7:2192–2202. doi:10.1158/1535-7163.MCT-08-033318645028
  • ZhouW, XuJ, LiH, et al. Neddylation E2 UBE2F promotes the survival of lung cancer cells by activating CRL5 to degrade NOXA via the K11 linkage. Clin Cancer Res. 2017;23:1104–1116. doi:10.1158/1078-0432.CCR-16-158527591266
  • WuX, LuoQ, LiuZ. Ubiquitination and deubiquitination of MCL1 in cancer: deciphering chemoresistance mechanisms and providing potential therapeutic options. Cell Death Dis. 2020;11(7):556. doi:10.1038/s41419-020-02760-y32699213
  • WertzIE, KusamS, LamC, et al. Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature. 2011;471(7336):110–114. doi:10.1038/nature0977921368834
  • DingQ, HeX, HsuJ-M, et al. Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol Cell Biol. 2007;27:4006–4017. doi:10.1128/MCB.00620-0617387146
  • ChoudharyGS, Al-HarbiS, MazumderS, et al. MCL-1 and BCL-xL-dependent resistance to the BCL-2 inhibitor ABT-199 can be overcome by preventing PI3K/AKT/mTOR activation in lymphoid malignancies. Cell Death Dis. 2015;6:e1593. doi:10.1038/cddis.2014.52525590803
  • MazumderS, ChoudharyGS, Al-HarbiS, AlmasanA. Mcl-1 phosphorylation defines ABT-737 resistance that can be overcome by increased NOXA expression in leukemic B cells. Cancer Res. 2012;72(12):3069–3079. doi:10.1158/0008-5472.CAN-11-410622525702
  • YamaguchiR, PerkinsG. Mcl-1 levels need not be lowered for cells to be sensitized for ABT-263/737-induced apoptosis. Cell Death Dis. 2011;2:e227. doi:10.1038/cddis.2011.10922071632
  • YeciesD, CarlsonNE, DengJ, LetaiA. Acquired resistance to ABT-737 in lymphoma cells that up-regulate MCL-1 and BFL-1. Blood. 2010;115(16):3304–3313. doi:10.1182/blood-2009-07-23330420197552
  • KotschyA, SzlavikZ, MurrayJ, et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature. 2016;538:477–482. doi:10.1038/nature1983027760111
  • Tai-ShunL, SchinaziRF, ZhuJ, et al. Anti-HIV-1 activity and cellular pharmacology of various analogs of gossypol. Biochem Pharmacol. 1993;46(2):251–255. doi:10.1016/0006-2952(93)90411-O8347147
  • ZhaoY, XiongX, SunY. Cullin-RING ligase 5: functional characterization and its role in human cancers. Semin Cancer Biol. 2020;67:61–79. doi:10.1016/j.semcancer.2020.04.00332334051