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  3. Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents)
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Volume 24, Issue 18
  • ISSN: 1871-5206
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Abstract

Background

The incidence of lung cancer is steadily on the rise, posing a growing threat to human health. The search for therapeutic drugs from natural active substances and elucidating their mechanism have been the focus of anti-tumor research.

Objective

Silibinin (SiL) has been shown to be a natural product with a wide range of pharmacological activities, including anti-tumour activity. In our work, SiL was chosen as a possible substance that could inhibit lung cancer. Moreover, its effects on inducing tumor cell death were also studied.

Methods

CCK-8 analysis and morphological observation were used to assess the cytotoxic impacts of SiL on lung cancer cells . The alterations in mitochondrial membrane potential (MMP) and apoptosis rate of cells were detected by flow cytometry. The level of lactate dehydrogenase (LDH) release out of cells was measured. The expression changes of apoptosis or necroptosis-related proteins were detected using western blotting. Protein interactions among RIPK1, RIPK3, and MLKL were analyzed using the co-immunoprecipitation (co-IP) technique. Necrosulfonamide (Nec, an MLKL inhibitor) was used to carry out experiments to assess the changes in apoptosis following the blockade of cell necroptosis. , SiL was evaluated for its antitumor effects using LLC tumor-bearing mice with mouse lung cancer.

Results

With an increased dose of SiL, the proliferation ability of A549 cells was considerably inhibited, and the accompanying cell morphology changed. The results of flow cytometry showed that after SiL treatment, MMP levels decreased, and the proportion of cells undergoing apoptosis increased. There was an increase in cleaved caspase-9, caspase-3, and PARP, with a down-regulation of Bcl-2 and an up-regulation of Bax. In addition, the amount of LDH released from the cells increased following SiL treatment, accompanied by augmented expression and phosphorylation levels of necroptosis-related proteins (MLKL, RIPK1, and RIPK3), and the co-IP assay further confirmed the interactions among these three proteins, indicating the necrosome formation induced by SiL. Furthermore, Nec increased the apoptotic rate of SiL-treated cells and aggravated the cytotoxic effect of SiL, indicating that necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL on A549 cells. In LLC-bearing mice, gastric administration of SiL significantly inhibited tumor growth, and H&E staining showed significant damage to the tumour tissue. The results of the IHC showed that the expression of RIPK1, RIPK3, and MLKL was more pronounced in the tumor tissue.

Conclusion

This study confirmed the dual effect of SiL, as it can induce both biological processes, apoptosis and necroptosis, in lung cancer. SiL-induced apoptosis involved the mitochondrial pathway, as indicated by changes in caspase-9, Bcl-2, and Bax. Necroptosis may be activated due to the changes in the expression of associated proteins in tumour cells and tissues. It has been observed that blocking necroptosis by SiL increased cell death efficiency. This study helps clarify the anti-tumor mechanism of SiL against lung cancer, elucidating its role in the dual induction of apoptosis and necroptosis. Our work provides an experimental basis for the research on cell death induced by SiL and reveals its possible applications for improving the management of lung cancer.

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2024-11-01
2024-11-29

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References

  1. BrayF. LaversanneM. SungH. FerlayJ. SiegelR.L. SoerjomataramI. JemalA. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202474322926310.3322/caac.21834 38572751
     [Google Scholar]
  2. SahuP. DonovanC. PaudelK.R. PicklesS. ChimankarV. KimR.Y. HorvartJ.C. DuaK. IeniA. NuceraF. Bielefeldt-OhmannH. MazilliS. CaramoriG. LyonsJ.G. HansbroP.M. Pre-clinical lung squamous cell carcinoma mouse models to identify novel biomarkers and therapeutic interventions.Front. Oncol.202313126041110.3389/fonc.2023.1260411 37817767
     [Google Scholar]
  3. AndoK. KishinoY. HommaT. KusumotoS. YamaokaT. TanakaA. OhmoriT. OhnishiT. SagaraH. Nivolumab plus Ipilimumab versus existing immunotherapies in patients with PD-L1-positive advanced non-small cell lung cancer: A systematic review and network meta-analysis.Cancers (Basel)2020127190510.3390/cancers12071905 32679702
     [Google Scholar]
  4. Lemjabbar-AlaouiH. HassanO.U. YangY.W. BuchananP. Lung cancer: Biology and treatment options.Biochim. Biophys. Acta201518562189210 26297204
     [Google Scholar]
  5. MottT.F. Lung Cancer: Management.FP Essent.20184642730 29313655
     [Google Scholar]
  6. HirschF.R. ScagliottiG.V. MulshineJ.L. KwonR. CurranW.J.Jr WuY.L. Paz-AresL. Lung cancer: current therapies and new targeted treatments.Lancet20173891006629931110.1016/S0140‑6736(16)30958‑8 27574741
     [Google Scholar]
  7. ShiK. WangG. PeiJ. ZhangJ. WangJ. OuyangL. WangY. LiW. Emerging strategies to overcome resistance to third-generation EGFR inhibitors.J. Hematol. Oncol.20221519410.1186/s13045‑022‑01311‑6 35840984
     [Google Scholar]
  8. SinghS. SadhukhanS. SonawaneA. 20 years since the approval of first EGFR-TKI, gefitinib: Insight and foresight.Biochim. Biophys. Acta Rev. Cancer20231878618896710.1016/j.bbcan.2023.188967 37657684
     [Google Scholar]
  9. ZhangJ. LiuS. ChenX. XuX. XuF. Non-immune cell components in tumor microenvironment influencing lung cancer Immunotherapy.Biomed. Pharmacother.202316611533610.1016/j.biopha.2023.115336 37591126
     [Google Scholar]
  10. ZhangM. ChenX. RadacsiN. New tricks of old drugs: Repurposing non-chemo drugs and dietary phytochemicals as adjuvants in anti-tumor therapies.J. Control. Release20213299612010.1016/j.jconrel.2020.11.047 33259852
     [Google Scholar]
  11. Al-YozbakiM. WilkinP.J. GuptaG.K. WilsonC.M. Therapeutic potential of natural compounds in lung cancer.Curr. Med. Chem.202128397988800210.2174/0929867328666210322103906 33749551
     [Google Scholar]
  12. NaeemA. HuP. YangM. ZhangJ. LiuY. ZhuW. ZhengQ. Natural products as anticancer agents: Current status and future perspectives.Molecules20222723836710.3390/molecules27238367 36500466
     [Google Scholar]
  13. TalibW.H. AwajanD. HamedR.A. AzzamA.O. MahmodA.I. AL-Yasari, I.H. Combination anticancer therapies using selected phytochemicals.Molecules20222717545210.3390/molecules27175452 36080219
     [Google Scholar]
  14. Bosch-BarreraJ. QueraltB. MenendezJ.A. Targeting STAT3 with silibinin to improve cancer therapeutics.Cancer Treat. Rev.201758616910.1016/j.ctrv.2017.06.003 28686955
     [Google Scholar]
  15. FanoudiS. AlaviM.S. KarimiG. HosseinzadehH. Milk thistle (Silybum Marianum) as an antidote or a protective agent against natural or chemical toxicities: A review.Drug Chem. Toxicol.202043324025410.1080/01480545.2018.1485687 30033764
     [Google Scholar]
  16. KřenV. ValentováK. Silybin and its congeners: from traditional medicine to molecular effects.Nat. Prod. Rep.20223961264128110.1039/D2NP00013J 35510639
     [Google Scholar]
  17. AbenavoliL. IzzoA.A. MilićN. CicalaC. SantiniA. CapassoR. Milk thistle (Silybum marianum): A concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases.Phytother. Res.201832112202221310.1002/ptr.6171 30080294
     [Google Scholar]
  18. WadhwaK. PahwaR. KumarM. KumarS. SharmaP.C. SinghG. VermaR. MittalV. SinghI. KaushikD. JeandetP. Mechanistic insights into the pharmacological significance of Silymarin.Molecules20222716532710.3390/molecules27165327 36014565
     [Google Scholar]
  19. ZiX. GrassoA.W. KungH.J. AgarwalR. A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells.Cancer Res.199858919201929 9581834
     [Google Scholar]
  20. ZiX. AgarwalR. Silibinin decreases prostate-specific antigen with cell growth inhibition via G 1 arrest, leading to differentiation of prostate carcinoma cells: Implications for prostate cancer intervention.Proc. Natl. Acad. Sci. USA199996137490749510.1073/pnas.96.13.7490 10377442
     [Google Scholar]
  21. FallahM. DavoodvandiA. NikmanzarS. AghiliS. MirazimiS.M.A. AschnerM. RashidianA. HamblinM.R. ChamanaraM. NaghshN. MirzaeiH. Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer.Biomed. Pharmacother.202114211202410.1016/j.biopha.2021.112024 34399200
     [Google Scholar]
  22. IqbalM.A. ChattopadhyayS. SiddiquiF.A. Ur RehmanA. SiddiquiS. PrakasamG. KhanA. SultanaS. BamezaiR.N.K. Silibinin induces metabolic crisis in triple‐negative breast cancer cells by modulating EGFR‐MYC‐TXNIP axis: Potential therapeutic implications.FEBS J.2021288247148510.1111/febs.15353 32356386
     [Google Scholar]
  23. JafariS. HeydarianS. LaiR. MehdizadehA.E. MolaviO. Silibinin induces immunogenic cell death in cancer cells and enhances the induced immunogenicity by chemotherapy.Bioimpacts2023131516110.34172/bi.2022.23698 36816998
     [Google Scholar]
  24. TuliH.S. MittalS. AggarwalD. ParasharG. ParasharN.C. UpadhyayS.K. BarwalT.S. JainA. KaurG. SavlaR. SakK. KumarM. VarolM. IqubalA. SharmaA.K. Path of Silibinin from diet to medicine: A dietary polyphenolic flavonoid having potential anti-cancer therapeutic significance.Semin. Cancer Biol.20217319621810.1016/j.semcancer.2020.09.014 33130037
     [Google Scholar]
  25. VerduraS. CuyàsE. Ruiz-TorresV. MicolV. JovenJ. Bosch-BarreraJ. MenendezJ.A. Lung cancer management with silibinin: A historical and translational perspective.Pharmaceuticals (Basel)202114655910.3390/ph14060559 34208282
     [Google Scholar]
  26. SiL. FuJ. LiuW. HayashiT. MizunoK. HattoriS. FujisakiH. OnoderaS. IkejimaT. Silibinin-induced mitochondria fission leads to mitophagy, which attenuates silibinin-induced apoptosis in MCF-7 and MDA-MB-231 cells.Arch. Biochem. Biophys.202068510828410.1016/j.abb.2020.108284 32014401
     [Google Scholar]
  27. MaoY.X. CaiW.J. SunX.Y. DaiP.P. LiX.M. WangQ. HuangX.L. HeB. WangP.P. WuG. MaJ.F. HuangS.B. RAGE-dependent mitochondria pathway: a novel target of silibinin against apoptosis of osteoblastic cells induced by advanced glycation end products.Cell Death Dis.20189667410.1038/s41419‑018‑0718‑3 29867140
     [Google Scholar]
  28. HamJ. LimW. BazerF.W. SongG. Silibinin stimluates apoptosis by inducing generation of ROS and ER stress in human choriocarcinoma cells.J. Cell. Physiol.201823321638164910.1002/jcp.26069 28657208
     [Google Scholar]
  29. ZengJ. SunY. WuK. LiL. ZhangG. YangZ. WangZ. ZhangD. XueY. ChenY. ZhuG. WangX. HeD. Chemopreventive and chemotherapeutic effects of intravesical silibinin against bladder cancer by acting on mitochondria.Mol. Cancer Ther.201110110411610.1158/1535‑7163.MCT‑10‑0577 21220495
     [Google Scholar]
  30. SameriS. MohammadiC. MehrabaniM. NajafiR. Targeting the hallmarks of cancer: the effects of silibinin on proliferation, cell death, angiogenesis, and migration in colorectal cancer.BMC Complementary Med. Ther.202121116010.1186/s12906‑021‑03330‑1 34059044
     [Google Scholar]
  31. JahanafroozZ. MotamedN. RinnerB. MokhtarzadehA. BaradaranB. Silibinin to improve cancer therapeutic, as an apoptotic inducer, autophagy modulator, cell cycle inhibitor, and microRNAs regulator.Life Sci.201821323624710.1016/j.lfs.2018.10.009 30308184
     [Google Scholar]
  32. MateenS. RainaK. AgarwalR. Chemopreventive and anti-cancer efficacy of silibinin against growth and progression of lung cancer.Nutr. Cancer201365Suppl. 131110.1080/01635581.2013.785004
     [Google Scholar]
  33. LinsF.V. BispoE.C.I. RodriguesN.S. SilvaM.V.S. CarvalhoJ.L. GelfusoG.M. Saldanha-AraujoF. Ibrutinib modulates proliferation, migration, mitochondrial homeostasis, and apoptosis in melanoma Cells.Biomedicines2024125101210.3390/biomedicines12051012 38790974
     [Google Scholar]
  34. RostampourS. EslamiF. BabaeiE. MostafaviH. MahdaviM. An active compound from the pyrazine family induces apoptosis by targeting the Bax/Bcl2 and Survivin expression in chronic myeloid leukemia K562 cells.Anticancer. Agents Med. Chem.202424320321210.2174/0118715206272359231121105713 38038011
     [Google Scholar]
  35. ÖzerkanD. The Determination of cisplatin and luteolin synergistic effect on colorectal cancer cell apoptosis and mitochondrial dysfunction by fluorescence labelling.J. Fluoresc.20233331217122510.1007/s10895‑023‑03145‑y 36652047
     [Google Scholar]
  36. ZhangL.N. XiaY.Z. ZhangC. ZhangH. LuoJ.G. YangL. KongL.Y. Vielanin K enhances doxorubicin-induced apoptosis via activation of IRE1α- TRAF2 - JNK pathway and increases mitochondrial Ca2 + influx in MCF-7 and MCF-7/MDR cells.Phytomedicine20207815332910.1016/j.phymed.2020.153329 32896708
     [Google Scholar]
  37. ZangW. CaoH. GeJ. ZhaoD. Structures, physical properties and antibacterial activity of silver nanoparticles of Lactiplantibacillus plantarum exopolysaccharide.Int. J. Biol. Macromol.2024263Pt 213008310.1016/j.ijbiomac.2024.130083 38423905
     [Google Scholar]
  38. DelmasD. XiaoJ. VejuxA. AiresV. Silymarin and cancer: A dual strategy in both in chemoprevention and chemosensitivity.Molecules2020259200910.3390/molecules25092009 32344919
     [Google Scholar]
  39. DegterevA. HuangZ. BoyceM. LiY. JagtapP. MizushimaN. CunyG.D. MitchisonT.J. MoskowitzM.A. YuanJ. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.Nat. Chem. Biol.20051211211910.1038/nchembio711 16408008
     [Google Scholar]
  40. AiY. MengY. YanB. ZhouQ. WangX. The biochemical pathways of apoptotic, necroptotic, pyroptotic, and ferroptotic cell death.Mol. Cell202484117017910.1016/j.molcel.2023.11.040 38181758
     [Google Scholar]
  41. WendlochaD. KubinaR. KrzykawskiK. Mielczarek-PalaczA. Selected flavonols targeting cell death pathways in cancer therapy: The latest achievements in research on apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis.Nutrients2024168120110.3390/nu16081201 38674891
     [Google Scholar]
  42. ShiY. WuC. ShiJ. GaoT. MaH. LiL. ZhaoY. Protein phosphorylation and kinases: Potential therapeutic targets in necroptosis.Eur. J. Pharmacol.202497017650810.1016/j.ejphar.2024.176508 38493913
     [Google Scholar]
  43. GreenD.R. The coming decade of cell death research: Five riddles.Cell201917751094110710.1016/j.cell.2019.04.024 31100266
     [Google Scholar]
  44. SunL. WangH. WangZ. HeS. ChenS. LiaoD. WangL. YanJ. LiuW. LeiX. WangX. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase.Cell20121481-221322710.1016/j.cell.2011.11.031 22265413
     [Google Scholar]
  45. McNamaraD.E. QuaratoG. GuyC.S. GreenD.R. MoldoveanuT. Characterization of MLKL-mediated plasma membrane rupture in necroptosis.J. Vis. Exp.201813858088 30148498
     [Google Scholar]
  46. YangY. XieE. DuL. YangY. WuB. SunL. WangS. OuYangB. Positive Charges in the Brace Region Facilitate the Membrane Disruption of MLKL-NTR in Necroptosis.Molecules20212617519410.3390/molecules26175194 34500630
     [Google Scholar]
  47. WeineltN. WächtershäuserK.N. CelikG. JeilerB. GollinI. ZeinL. SmithS. AndrieuxG. DasT. RoedigJ. FeistL. RotterB. BoerriesM. PampaloniF. van WijkS.J.L. LUBAC-mediated M1 Ub regulates necroptosis by segregating the cellular distribution of active MLKL.Cell Death Dis.20241517710.1038/s41419‑024‑06447‑6 38245534
     [Google Scholar]
  48. RamirezR.X. CampbellO. PradhanA.J. Atilla-GokcumenG.E. Monje-GalvanV. Modeling the molecular fingerprint of protein-lipid interactions of MLKL on complex bilayers.Front Chem.202310108805810.3389/fchem.2022.1088058 36712977
     [Google Scholar]
  49. ZhaoJ. JitkaewS. CaiZ. ChoksiS. LiQ. LuoJ. LiuZ.G. Mixed lineage kinase domain-like is a key receptor interacting protein 3 downstream component of TNF-induced necrosis.Proc. Natl. Acad. Sci. USA2012109145322532710.1073/pnas.1200012109 22421439
     [Google Scholar]
  50. WangN. LiC.Y. YaoT.F. KangX.D. GuoH.S. OSW-1 triggers necroptosis in colorectal cancer cells through the RIPK1/RIPK3/MLKL signaling pathway facilitated by the RIPK1-p62/SQSTM1 complex.World J. Gastroenterol.202430152155217410.3748/wjg.v30.i15.2155 38681991
     [Google Scholar]
  51. GuanS. QuX. WangJ. ZhangD. LuJ. 3-Monochloropropane-1,2-diol esters induce HepG2 cells necroptosis via CTSB/TFAM/ROS pathway.Food Chem. Toxicol.202418611452510.1016/j.fct.2024.114525 38408632
     [Google Scholar]
  52. ZhangY. ZhouX. Targeting regulated cell death (RCD) in hematological malignancies: Recent advances and therapeutic potential.Biomed. Pharmacother.202417511666710.1016/j.biopha.2024.116667 38703504
     [Google Scholar]
  53. LiuR.J. YuX.D. YanS.S. GuoZ.W. ZaoX.B. ZhangY.S. Ferroptosis, pyroptosis and necroptosis in hepatocellular carcinoma immunotherapy: Mechanisms and immunologic landscape (Review).Int. J. Oncol.20246466310.3892/ijo.2024.5651 38757345
     [Google Scholar]
  54. NajafovA. ChenH. YuanJ. Necroptosis and cancer.Trends Cancer20173429430110.1016/j.trecan.2017.03.002 28451648
     [Google Scholar]
  55. YanJ. WanP. ChoksiS. LiuZ.G. Necroptosis and tumor progression.Trends Cancer202281212710.1016/j.trecan.2021.09.003 34627742
     [Google Scholar]
  56. ZangX. SongJ. LiY. HanY. Targeting necroptosis as an alternative strategy in tumor treatment: From drugs to nanoparticles.J. Control. Release202234921322610.1016/j.jconrel.2022.06.060 35793737
     [Google Scholar]
  57. LiuZ. JiaoD. Necroptosis, tumor necrosis and tumorigenesis.Cell Stress2020411810.15698/cst2020.01.208 31922095
     [Google Scholar]
  58. QinY. ShengY. RenM. HouZ. XiaoL. ChenR. Identification of necroptosis-related gene signatures for predicting the prognosis of ovarian cancer.Sci. Rep.20241411113310.1038/s41598‑024‑61849‑y 38750159
     [Google Scholar]
  59. ChongL.H. YipA.K. FarmH.J. MahmoudL.N. ZengY. ChiamK.H. The role of cell-matrix adhesion and cell migration in breast tumor growth and progression.Front. Cell Dev. Biol.202412133925110.3389/fcell.2024.1339251 38374894
     [Google Scholar]
  60. HöckendorfU. YabalM. HeroldT. MunkhbaatarE. RottS. JilgS. KauschingerJ. MagnaniG. ReisingerF. HeuserM. KreipeH. SotlarK. EngleitnerT. RadR. WeichertW. PeschelC. RulandJ. HeikenwalderM. SpiekermannK. Slotta-HuspeninaJ. GroßO. JostP.J. RIPK3 restricts myeloid leukemogenesis by promoting cell death and differentiation of leukemia initiating cells.Cancer Cell2016301759110.1016/j.ccell.2016.06.002 27411587
     [Google Scholar]
  61. SeifertL. WerbaG. TiwariS. Giao LyN.N. AlothmanS. AlqunaibitD. AvanziA. BarillaR. DaleyD. GrecoS.H. Torres-HernandezA. PergamoM. OchiA. ZambirinisC.P. PansariM. RendonM. TippensD. HundeyinM. ManiV.R. HajduC. EngleD. MillerG. The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression.Nature2016532759824524910.1038/nature17403 27049944
     [Google Scholar]
  62. SeehawerM. HeinzmannF. D’ArtistaL. HarbigJ. RouxP.F. HoenickeL. DangH. KlotzS. RobinsonL. DoréG. RozenblumN. KangT.W. ChawlaR. BuchT. VucurM. RothM. ZuberJ. LueddeT. SiposB. LongerichT. HeikenwälderM. WangX.W. BischofO. ZenderL. Necroptosis microenvironment directs lineage commitment in liver cancer.Nature20185627725697510.1038/s41586‑018‑0519‑y 30209397
     [Google Scholar]
  63. QinX. MaD. TanY. WangH. CaiZ. The role of necroptosis in cancer: A double-edged sword?Biochim. Biophys. Acta Rev. Cancer20191871225926610.1016/j.bbcan.2019.01.006 30716362
     [Google Scholar]
  64. XueY. JiangX. WangJ. ZongY. YuanZ. MiaoS. MaoX. Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma.Biomark. Res.2023111210.1186/s40364‑022‑00433‑w 36600313
     [Google Scholar]
  65. ScimecaM. RovellaV. PalumboV. ScioliM.P. BonfiglioR. MelinoG. PiacentiniM. FratiL. AgostiniM. CandiE. MaurielloA. Tor, Centre.; Melino, G.; Piacentini, M.; Frati, L.; Agostini, M.; Candi, E.; Mauriello, A. Programmed cell death pathways in cholangiocarcinoma: Opportunities for targeted therapy.Cancers (Basel)20231514363810.3390/cancers15143638 37509299
     [Google Scholar]
  66. ThijssenR. Alvarez-DiazS. GraceC. GaoM. SegalD.H. XuZ. StrasserA. HuangD.C.S. Loss of RIPK3 does not impact MYC-driven lymphomagenesis or chemotherapeutic drug-induced killing of malignant lymphoma cells.Cell Death Differ.20202782531253310.1038/s41418‑020‑0576‑2 32555451
     [Google Scholar]
  67. RenaudC.C.N. NicolauC.A. MagheC. TrilletK. JardineJ. EscotS. DavidN. GavardJ. BidèreN. Necrosulfonamide causes oxidation of PCM1 and impairs ciliogenesis and autophagy.iScience202427410958010.1016/j.isci.2024.109580 38600973
     [Google Scholar]
  68. TangY. ZhuangC. Design, synthesis and anti-necroptosis activity of fused heterocyclic MLKL inhibitors.Bioorg. Med. Chem.202410211765910.1016/j.bmc.2024.117659 38442525
     [Google Scholar]
  69. OhJ.H. ParkS. HongE. ChoiM.A. KwonY.M. ParkJ. LeeA.H. ParkG.R. KimH.Y. LeeS.M. LeeJ.Y. BaeS.H. LeeJ.H. LeeJ.Y. JunD.W. Novel inhibitor of mixed-lineage kinase domain-like protein: The antifibrotic effects of a necroptosis antagonist.ACS Pharmacol. Transl. Sci.20236101471147910.1021/acsptsci.3c00131 37854622
     [Google Scholar]
  70. TongK. LiS. ChenG. MaC. LiuX. LiuS. ChenN. Inhibition of neural stem cell necroptosis mediated by RIPK1/MLKL promotes functional recovery after SCI.Mol. Neurobiol.20236042135214910.1007/s12035‑022‑03156‑z 36602703
     [Google Scholar]
  71. JiaoD. CaiZ. ChoksiS. MaD. ChoeM. KwonH.J. BaikJ.Y. RowanB.G. LiuC. LiuZ. Necroptosis of tumor cells leads to tumor necrosis and promotes tumor metastasis.Cell Res.201828886887010.1038/s41422‑018‑0058‑y 29941926
     [Google Scholar]
  72. LiuZ. ChoksiS. KwonH.J. JiaoD. LiuC. LiuZ. Tumor necroptosis-mediated shedding of cell surface proteins promotes metastasis of breast cancer by suppressing anti-tumor immunity.Breast Cancer Res.20232511010.1186/s13058‑023‑01604‑9 36703228
     [Google Scholar]
  73. LiF. SunH. YuY. CheN. HanJ. ChengR. ZhaoN. GuoY. HuangC. ZhangD. RIPK1-dependent necroptosis promotes vasculogenic mimicry formation via eIF4E in triple-negative breast cancer.Cell Death Dis.202314533510.1038/s41419‑023‑05841‑w 37217473
     [Google Scholar]
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Silibinin Induces Both Apoptosis and Necroptosis with Potential Anti-tumor Efficacy in Lung Cancer
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 24, 1327 (2024); https://doi.org/10.2174/0118715206295371240724092314
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  • Article Type:     Research Article
Keyword(s): apoptosis; cell death; lung cancer; mitochondria; MLKL; necroptosis; Silibinin

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