Skip to content
2000
Volume 26, Issue 1
  • ISSN: 1389-4501
  • E-ISSN: 1873-5592

Abstract

SERCA2, a P-type ATPase located on the endoplasmic reticulum of cells, plays an important role in maintaining calcium balance within cells by transporting calcium from the cytoplasm to the endoplasmic reticulum against its concentration gradient. A multitude of studies have demonstrated that the expression of SERCA2 is abnormal in a wide variety of tumor cells. Consequently, research exploring compounds that target SERCA2 may offer a promising avenue for the development of novel anti-tumor drugs. This review has summarized the anti-tumor compounds targeting SERCA2, including thapsigargin, dihydroartemisinin, curcumin, galangin, These compounds interact with SERCA2 on the endoplasmic reticulum membrane, disrupting intracellular calcium ion homeostasis, leading to tumor cell apoptosis, autophagy and cell cycle arrest, ultimately producing anti-tumor effects. Additionally, several potential research directions for compounds targeting SERCA2 as clinical anti-cancer drugs have been proposed in the review. In summary, SERCA2 is a promising anti-tumor target for drug discovery and development.

Loading

Article metrics loading...

/content/journals/cdt/10.2174/0113894501325497240918042654
2025-09-25
2025-01-13
Loading full text...

Full text loading...

References

  1. TorreL.A. SiegelR.L. WardE.M. JemalA. Global cancer incidence and mortality rates and trends — An update.Cancer Epidemiol. Biomarkers Prev.2016251162710.1158/1055‑9965.EPI‑15‑057826667886
    [Google Scholar]
  2. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.2166033538338
    [Google Scholar]
  3. WuC. LiM. MengH. LiuY. NiuW. ZhouY. ZhaoR. DuanY. ZengZ. LiX. LiG. XiongW. ZhouM. Analysis of status and countermeasures of cancer incidence and mortality in China.Sci. China Life Sci.201962564064710.1007/s11427‑018‑9461‑530900169
    [Google Scholar]
  4. CohenJ.B. BrownN.J. BrownS.A. DentS. van DorstD.C.H. HerrmannS.M. LangN.N. OuditG.Y. TouyzR.M. Cancer therapy–related hypertension: A scientific statement from the american heart association.Hypertension2023803e46e5710.1161/HYP.000000000000022436621810
    [Google Scholar]
  5. Shyam SunderS. SharmaU.C. PokharelS. Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management.Signal Transduct. Target. Ther.20238126210.1038/s41392‑023‑01469‑637414756
    [Google Scholar]
  6. PranziniE. PardellaE. MuccilloL. LeoA. NesiI. SantiA. ParriM. ZhangT. UribeA.H. LottiniT. SabatinoL. CaselliA. ArcangeliA. RaugeiG. ColantuoniV. CirriP. ChiarugiP. MaddocksO.D.K. PaoliP. TaddeiM.L. SHMT2-mediated mitochondrial serine metabolism drives 5-FU resistance by fueling nucleotide biosynthesis.Cell Rep.202240711123310.1016/j.celrep.2022.11123335977477
    [Google Scholar]
  7. ChambersP.J. JuracicE.S. FajardoV.A. TuplingA.R. Role of SERCA and sarcolipin in adaptive muscle remodeling.Am. J. Physiol. Cell Physiol.20223223C382C39410.1152/ajpcell.00198.202135044855
    [Google Scholar]
  8. RodriguezJ.B.R. Muzi-FilhoH. ValverdeR.H.F. QuintasL.E.M. NoelF. Einicker-LamasM. CunhaV.M.N. Rat vas deferens SERCA2 is modulated by Ca2+/calmodulin protein kinase II-mediated phosphorylation.Braz. J. Med. Biol. Res.201346322723410.1590/1414‑431X2012261623558856
    [Google Scholar]
  9. GorskiP.A. CeholskiD.K. YoungH.S. Structure-function relationship of the SERCA pump and its regulation by phospholamban and sarcolipin.Adv. Exp. Med. Biol.20179817711910.1007/978‑3‑319‑55858‑5_529594859
    [Google Scholar]
  10. ArbabianA. BroulandJ.P. GélébartP. KovàcsT. BobeR. EnoufJ. PappB. Endoplasmic reticulum calcium pumps and cancer.Biofactors201137313914910.1002/biof.14221674635
    [Google Scholar]
  11. FanM. GaoJ. ZhouL. XueW. WangY. ChenJ. LiW. YuY. LiuB. ShenY. XuQ. Highly expressed SERCA2 triggers tumor cell autophagy and is a druggable vulnerability in triple-negative breast cancer.Acta Pharm. Sin. B202212124407442310.1016/j.apsb.2022.05.00936561988
    [Google Scholar]
  12. SehgalP. SzalaiP. OlesenC. PraetoriusH.A. NissenP. ChristensenS.B. EngedalN. MøllerJ.V. Inhibition of the sarco/endoplasmic reticulum (ER) Ca2+-ATPase by thapsigargin analogs induces cell death via ER Ca2+ depletion and the unfolded protein response.J. Biol. Chem.201729248196561967310.1074/jbc.M117.79692028972171
    [Google Scholar]
  13. MahalingamD. WildingG. DenmeadeS. SarantopoulasJ. CosgroveD. CetnarJ. AzadN. BruceJ. KurmanM. AllgoodV.E. CarducciM. Mipsagargin, a novel thapsigargin-based PSMA-activated prodrug: Results of a first-in-man phase I clinical trial in patients with refractory, advanced or metastatic solid tumours.Br. J. Cancer2016114998699410.1038/bjc.2016.7227115568
    [Google Scholar]
  14. ZhangY. InabaK. Structural basis of the conformational and functional regulation of human SERCA2b, the ubiquitous endoplasmic reticulum calcium pump.BioEssays2022447220005210.1002/bies.20220005235560336
    [Google Scholar]
  15. MøllerJ.V. OlesenC. WintherA.M.L. NissenP. The sarcoplasmic Ca2+ -ATPase: Design of a perfect chemi-osmotic pump.Q. Rev. Biophys.201043450156610.1017/S003358351000017X20809990
    [Google Scholar]
  16. ToyoshimaC. NomuraH. Structural changes in the calcium pump accompanying the dissociation of calcium.Nature2002418689860561110.1038/nature0094412167852
    [Google Scholar]
  17. ToyoshimaC. MizutaniT. Crystal structure of the calcium pump with a bound ATP analogue.Nature2004430699952953510.1038/nature0268015229613
    [Google Scholar]
  18. SmolinN. RobiaS.L. A structural mechanism for calcium transporter headpiece closure.J. Phys. Chem. B201511941407141510.1021/jp511433v25531267
    [Google Scholar]
  19. BritzolakiA. SaurineJ. KlockeB. PitychoutisP.M. A role for SERCA Pumps in the neurobiology of neuropsychiatric and neurodegenerative disorders.Adv. Exp. Med. Biol.2020113113116110.1007/978‑3‑030‑12457‑1_631646509
    [Google Scholar]
  20. MusgaardM. ThøgersenL. SchiøttB. Protonation states of important acidic residues in the central Ca2+ ion binding sites of the Ca2+-ATPase: A molecular modeling study.Biochemistry20115051111091112010.1021/bi201164b22082179
    [Google Scholar]
  21. Aguayo-OrtizR. Espinoza-FonsecaL.M. Linking biochemical and structural states of SERCA: Achievements, challenges, and new opportunities.Int. J. Mol. Sci.20202111414610.3390/ijms2111414632532023
    [Google Scholar]
  22. ToyoshimaC. CorneliusF. New crystal structures of PII-type ATPases: Excitement continues.Curr. Opin. Struct. Biol.201323450751410.1016/j.sbi.2013.06.00523871101
    [Google Scholar]
  23. BublitzM. PoulsenH. MorthJ.P. NissenP. In and out of the cation pumps: P-Type ATPase structure revisited.Curr. Opin. Struct. Biol.201020443143910.1016/j.sbi.2010.06.00720634056
    [Google Scholar]
  24. AnderssonJ. HauserK. KarjalainenE.L. BarthA. Protonation and hydrogen bonding of Ca2+ site residues in the E2P phosphoenzyme intermediate of sarcoplasmic reticulum Ca2+-ATPase studied by a combination of infrared spectroscopy and electrostatic calculations.Biophys. J.200894260061110.1529/biophysj.107.11403317890386
    [Google Scholar]
  25. VangheluweP. SepúlvedaM.R. MissiaenL. RaeymaekersL. WuytackF. VanoevelenJ. Intracellular Ca2+ - and Mn2+ -Transport ATPases.Chem. Rev.2009109104733475910.1021/cr900013m19678701
    [Google Scholar]
  26. Kekenes-HuskeyP.M. MetzgerV.T. GrantB.J. Andrew McCammonJ. Calcium binding and allosteric signaling mechanisms for the sarcoplasmic reticulum Ca2+ ATPase.Protein Sci.201221101429144310.1002/pro.212922821874
    [Google Scholar]
  27. ToyoshimaC. How Ca2+-ATPase pumps ions across the sarcoplasmic reticulum membrane.Biochim. Biophys. Acta Mol. Cell Res.20091793694194610.1016/j.bbamcr.2008.10.00819010358
    [Google Scholar]
  28. WuytackF. RaeymaekersL. MissiaenL. Molecular physiology of the SERCA and SPCA pumps.Cell Calcium2002325-627930510.1016/S014341600200184712543090
    [Google Scholar]
  29. ZhihaoL. JingyuN. LanL. MichaelS. RuiG. XiyunB. XiaozhiL. GuanweiF. SERCA2a: A key protein in the Ca2+ cycle of the heart failure.Heart Fail. Rev.202025352353510.1007/s10741‑019‑09873‑331701344
    [Google Scholar]
  30. VandecaetsbeekI. VangheluweP. RaeymaekersL. WuytackF. VanoevelenJ. The Ca2+ pumps of the endoplasmic reticulum and Golgi apparatus.Cold Spring Harb. Perspect. Biol.201135a00418410.1101/cshperspect.a00418421441596
    [Google Scholar]
  31. GorskiP.A. TrieberC.A. LarivièreE. SchuermansM. WuytackF. YoungH.S. VangheluweP. Transmembrane helix 11 is a genuine regulator of the endoplasmic reticulum Ca2+ pump and acts as a functional parallel of β-subunit on α-Na+,K+-ATPase.J. Biol. Chem.201228724198761988510.1074/jbc.M111.33562022528494
    [Google Scholar]
  32. GélébartP. MartinV. EnoufJ. PappB. Identification of a new SERCA2 splice variant regulated during monocytic differentiation.Biochem. Biophys. Res. Commun.2003303267668410.1016/S0006‑291X(03)00405‑412659872
    [Google Scholar]
  33. ParkK.C. KimS.W. JeonJ.Y. JoA.R. ChoiH.J. KimJ. LeeH.G. KimY. MillsG.B. NohS.H. LeeM.G. ParkE.S. CheongJ.H. Survival of cancer stem-like cells under metabolic stress via camk2α-mediated upregulation of sarco/endoplasmic reticulum calcium ATPase expression.Clin. Cancer Res.20182471677169010.1158/1078‑0432.CCR‑17‑221929279319
    [Google Scholar]
  34. SeoJ. KimB. DhanasekaranD.N. TsangB.K. SongY.S. Curcumin induces apoptosis by inhibiting sarco/endoplasmic reticulum Ca2+ ATPase activity in ovarian cancer cells.Cancer Lett.20163711303710.1016/j.canlet.2015.11.02126607901
    [Google Scholar]
  35. FanL. LiA. LiW. CaiP. YangB. ZhangM. GuY. ShuY. SunY. ShenY. WuX. HuG. WuX. XuQ. Novel role of Sarco/endoplasmic reticulum calcium ATPase 2 in development of colorectal cancer and its regulation by F36, a curcumin analog.Biomed. Pharmacother.20146881141114810.1016/j.biopha.2014.10.01425458791
    [Google Scholar]
  36. SunluH. LuM. Mechanism of dihydroartemisinin binding SERCA2b and inducing apoptosis in colorectal cell HCT-116.Zhongguo Yike Daxue Xuebao202416
    [Google Scholar]
  37. LiW. OuyangZ. ZhangQ. WangL. ShenY. WuX. GuY. ShuY. YuB. WuX. SunY. XuQ. SBF-1 exerts strong anticervical cancer effect through inducing endoplasmic reticulum stress-associated cell death via targeting sarco/endoplasmic reticulum Ca2+-ATPase 2.Cell Death Dis.2014512e158110.1038/cddis.2014.53825522275
    [Google Scholar]
  38. YangB. ZhangM. GaoJ. LiJ. FanL. XiangG. WangX. WangX. WuX. SunY. WuX. LiangG. ShenY. XuQ. Small molecule RL71 targets SERCA2 at a novel site in the treatment of human colorectal cancer.Oncotarget2015635376133762510.18632/oncotarget.606826608678
    [Google Scholar]
  39. ZhangL. ChengX. XuS. BaoJ. YuH. Curcumin induces endoplasmic reticulum stress-associated apoptosis in human papillary thyroid carcinoma BCPAP cells via disruption of intracellular calcium homeostasis.Medicine (Baltimore)20189724e1109510.1097/MD.000000000001109529901626
    [Google Scholar]
  40. WangL. WangL. SongR. ShenY. SunY. GuY. ShuY. XuQ. Targeting sarcoplasmic/endoplasmic reticulum Ca2+-ATPase 2 by curcumin induces ER stress-associated apoptosis for treating human liposarcoma.Mol. Cancer Ther.201110346147110.1158/1535‑7163.MCT‑10‑081221282356
    [Google Scholar]
  41. ChenC.C. ChenB.R. WangY. CurmanP. BeilinsonH.A. BrechtR.M. LiuC.C. FarrellR.J. de Juan-SanzJ. CharbonnierL.M. KajimuraS. RyanT.A. SchatzD.G. ChatilaT.A. WikstromJ.D. TylerJ.K. SleckmanB.P. Sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) activity is required for V(D)J recombination.J. Exp. Med.20212188e2020170810.1084/jem.2020170834033676
    [Google Scholar]
  42. IsaacsJ.T. BrennenW.N. ChristensenS.B. DenmeadeS.R. Mipsagargin: The beginning—not the end—of thapsigargin prodrug-based cancer therapeutics.Molecules20212624746910.3390/molecules2624746934946547
    [Google Scholar]
  43. ChenP. LiY. ZhouZ. PanC. ZengL. Lathyrol promotes ER stress-induced apoptosis and proliferation inhibition in lung cancer cells by targeting SERCA2.Biomed. Pharmacother.202315811412310.1016/j.biopha.2022.11412336521248
    [Google Scholar]
  44. WangR. WangY. NiuY. HeD. JinS. LiZ. ZhuL. ChenL. WuX. DingC. WuT. ShiX. ZhangH. LiC. WangX. XieZ. LiW. LiuY. Deep learning-predicted dihydroartemisinin rescues osteoporosis by maintaining mesenchymal stem cell stemness through activating histone 3 lys 9 acetylation.ACS Cent. Sci.20239101927194310.1021/acscentsci.3c0079437901168
    [Google Scholar]
  45. LeeA.Y. ParkJ.Y. ChunJ.M. MoonB.C. KangB.K. SeoY.B. ShinH.K. KimH.K. Optimization of extraction condition for alisol B and alisol B acetate in alismatis rhizoma using response surface methodology.J. Liq. Chromatogr. Relat. Technol.201336451352410.1080/10826076.2012.66873323335845
    [Google Scholar]
  46. KothaR.R. LuthriaD.L. Curcumin: Biological, pharmaceutical, nutraceutical, and analytical aspects.Molecules20192416293010.3390/molecules2416293031412624
    [Google Scholar]
  47. Deepika MauryaPK. Benefits of quercetin in age-related diseases.Molecules2022278249810.3390/molecules27082498
    [Google Scholar]
  48. HossainU. DasA.K. GhoshS. SilP.C. An overview on the role of bioactive α-glucosidase inhibitors in ameliorating diabetic complications.Food Chem. Toxicol.202014511173810.1016/j.fct.2020.11173832916220
    [Google Scholar]
  49. ZhaoZ. NianM. QiaoH. YangX. WuS. ZhengX. Review of bioactivity and structure-activity relationship on baicalein (5,6,7-trihydroxyflavone) and wogonin (5,7-dihydroxy-8-metho- xyflavone) derivatives: Structural modifications inspired from flavonoids in Scutellaria baicalensis.Eur. J. Med. Chem.202224311473310.1016/j.ejmech.2022.11473336155355
    [Google Scholar]
  50. ChagasM.S.S. BehrensM.D. Moragas-TellisC.J. PenedoG.X.M. SilvaA.R. Gonçalves-de-AlbuquerqueC.F. Flavonols and flavones as potential anti-inflammatory, antioxidant, and antibacterial compounds.Oxid. Med. Cell. Longev.2022202212110.1155/2022/996675036111166
    [Google Scholar]
  51. KurisawaN. IwasakiA. TeranumaK. DanS. ToyoshimaC. HashimotoM. SuenagaK. Structural determination, total synthesis, and biological activity of iezoside, a highly potent Ca2+ -ATPase inhibitor from the marine cyanobacterium Leptochromothrix valpauliae.J. Am. Chem. Soc.202214424110191103210.1021/jacs.2c0445935673891
    [Google Scholar]
  52. LvX. ZhangW. XiaS. HuangZ. ShiP. Clioquinol inhibits cell growth in a SERCA2-dependent manner.J. Biochem. Mol. Toxicol.2021355e2272710.1002/jbt.2272733511738
    [Google Scholar]
  53. JohnsonA.J. HsuA.L. LinH.P. SongX. ChenC.S. The cyclo-oxygenase-2 inhibitor celecoxib perturbs intracellular calcium by inhibiting endoplasmic reticulum Ca2+-ATPases: A plausible link with its anti-tumour effect and cardiovascular risks.Biochem. J.2002366383183710.1042/bj2002027912076251
    [Google Scholar]
  54. WangA. ZhengY. ZhuW. YangL. YangY. PengJ. Melittin-based nano-delivery systems for cancer therapy.Biomolecules202212111810.3390/biom1201011835053266
    [Google Scholar]
  55. IwasakiA. OhnoO. KatsuyamaS. MoritaM. SasazawaY. DanS. SimizuS. YamoriT. SuenagaK. Identification of a molecular target of kurahyne, an apoptosis-inducing lipopeptide from marine cyanobacterial assemblages.Bioorg. Med. Chem. Lett.201525225295529810.1016/j.bmcl.2015.09.04426428873
    [Google Scholar]
  56. HorngC.T. ChiangN.N. ChenI.L. LiangW.Z. ChenI.S. KuoD.H. ShiehP.C. JanC.R. Effect of clotrimazole on cytosolic Ca2+ rise and viability in HA59T human hepatoma cells.J. Recept. Signal Transduct. Res.2013332899510.3109/10799893.2013.76432123384009
    [Google Scholar]
  57. JaskulskaA. JaneckaA.E. Gach-JanczakK. Thapsigargin—from traditional medicine to anticancer drug.Int. J. Mol. Sci.2020221410.3390/ijms2201000433374919
    [Google Scholar]
  58. PeterkováL. KmoníčkováE. RumlT. RimpelováS. Sarco/endoplasmic reticulum calcium atpase inhibitors: beyond anticancer perspective.J. Med. Chem.20206351937196310.1021/acs.jmedchem.9b0150932030976
    [Google Scholar]
  59. LawB.Y.K. WangM. MaD.L. Al-MousaF. MichelangeliF. ChengS.H. NgM.H.L. ToK.F. MokA.Y.F. KoR.Y.Y. LamS.K. ChenF. CheC.M. ChiuP. KoB.C.B. Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis.Mol. Cancer Ther.20109371873010.1158/1535‑7163.MCT‑09‑070020197400
    [Google Scholar]
  60. ZhangJ. LiY. WangJ.G. FengJ.Y. HuangG.D. LuoC.G. Dihydroartemisinin affects STAT3/DDA1 signaling pathway and reverses breast cancer resistance to cisplatin.Am. J. Chin. Med.202351244545910.1142/S0192415X2350023436891981
    [Google Scholar]
  61. WangY. YangZ. ZhuW. ChenY. HeX. LiJ. HanZ. YangY. LiuW. ZhangK. Dihydroartemisinin inhibited stem cell-like properties and enhanced oxaliplatin sensitivity of colorectal cancer via AKT/mTOR signaling.Drug Dev. Res.202384598899810.1002/ddr.2206737132439
    [Google Scholar]
  62. MaY. ZhangP. ZhangQ. WangX. MiaoQ. LyuX. CuiB. MaH. Dihydroartemisinin suppresses proliferation, migration, the Wnt/β-catenin pathway and EMT via TNKS in gastric cancer.Oncol. Lett.202122468810.3892/ol.2021.1294934457043
    [Google Scholar]
  63. DaiX. ChenW. QiaoY. ChenX. ChenY. ZhangK. ZhangQ. DuanX. LiX. ZhaoJ. TianF. LiuK. DongZ. LuJ. Dihydroartemisinin inhibits the development of colorectal cancer by GSK-3β/TCF7/MMP9 pathway and synergies with capecitabine.Cancer Lett.202458221659610.1016/j.canlet.2023.21659638101610
    [Google Scholar]
  64. ImranM. RaufA. Abu-IzneidT. NadeemM. ShariatiM.A. KhanI.A. ImranA. Orhani.e. RizwanM. AtifM. GondalT.A. MubarakM.S. Luteolin, a flavonoid, as an anticancer agent: A review.Biomed. Pharmacother.201911210861210.1016/j.biopha.2019.10861230798142
    [Google Scholar]
  65. KuharM. SenS. SinghN. Role of mitochondria in quercetin-enhanced chemotherapeutic response in human non-small cell lung carcinoma H-520 cells.Anticancer Res.2006262A1297130316619537
    [Google Scholar]
  66. OgunbayoO.A. HarrisR.M. WaringR.H. KirkC.J. MichelangeliF. Inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+ -ATPase by flavonoids: A quantitative structure-activity relationship study.IUBMB Life2008601285385810.1002/iub.13218785622
    [Google Scholar]
  67. LuoY. XuC. LuoB. LiangG. ZhangQ. Melittin treatment prevents colorectal cancer from progressing in mice through ER stress-mediated apoptosis.J. Pharm. Pharmacol.202375564565410.1093/jpp/rgad00836966363
    [Google Scholar]
  68. BartolommeiG. Tadini-BuoninsegniF. HuaS. MoncelliM.R. InesiG. GuidelliR. Clotrimazole inhibits the Ca2+-ATPase (SERCA) by interfering with Ca2+ binding and favoring the E2 conformation.J. Biol. Chem.2006281149547955110.1074/jbc.M51055020016452481
    [Google Scholar]
  69. HuangH. ChenA.Y. YeX. GuanR. RankinG.O. ChenY.C. Galangin, a flavonoid from lesser galangal, induced apoptosis via p53-dependent pathway in ovarian cancer cells.Molecules2020257157910.3390/molecules2507157932235536
    [Google Scholar]
  70. HowellsL.M. IwujiC.O.O. IrvingG.R.B. BarberS. WalterH. SidatZ. Griffin-TeallN. SinghR. ForemanN. PatelS.R. MorganB. StewardW.P. GescherA. ThomasA.L. BrownK. Curcumin combined with FOLFOX chemotherapy is safe and tolerable in patients with metastatic colorectal cancer in a randomized phase IIa trial.J. Nutr.201914971133113910.1093/jn/nxz02931132111
    [Google Scholar]
  71. SøhoelH. LiljeforsT. LeyS.V. OliverS.F. AntonelloA. SmithM.D. OlsenC.E. IsaacsJ.T. ChristensenS.B. Total synthesis of two novel subpicomolar sarco/endoplasmatic reticulum Ca2+-ATPase inhibitors designed by an analysis of the binding site of thapsigargin.J. Med. Chem.200548227005701110.1021/jm058036v16250659
    [Google Scholar]
  72. LindnerP. ChristensenS.B. NissenP. MøllerJ.V. EngedalN. Cell death induced by the ER stressor thapsigargin involves death receptor 5, a non-autophagic function of MAP1LC3B, and distinct contributions from unfolded protein response components.Cell Commun. Signal.20201811210.1186/s12964‑019‑0499‑z31987044
    [Google Scholar]
  73. ZhangJ. HuangW. SunH. LiuY. ZhaoX. TangS. SunM. WangS. LiJ. ZhangL. ZhouJ. PanQ. ChenH. Structure identification and in vitro anticancer activity of lathyrol-3-phenylacetate-5,15-diacetate.Molecules2017229141210.3390/molecules2209141228841191
    [Google Scholar]
  74. ZhouXW. TanWF. XieFY. XinB. ChenJ. Research progress on anti-cancer pharmacological mechanism of dihydroartemisinin.J. Pharm. Pract.2019373206211
    [Google Scholar]
  75. MuD Study on the anti-lung cancer effect and mechanism of dihydroartemisinin.Thesis, Fourth military medical university of chinese2008
    [Google Scholar]
  76. OgunbayoO.A. MichelangeliF. Related flavonoids cause cooperative inhibition of the sarcoplasmic reticulum Ca2+ ATP ase by multimode mechanisms.FEBS J.2014281376677710.1111/febs.1262124238016
    [Google Scholar]
  77. LinY.T. YangJ.S. LinH.J. TanT.W. TangN.Y. ChaingJ.H. ChangY.H. LuH.F. ChungJ.G. Baicalein induces apoptosis in SCC-4 human tongue cancer cells via a Ca2+-dependent mitochondrial pathway. In vivo 20072161053105818210755
    [Google Scholar]
  78. LiK.S. HeM.L. PiR.B. LiuA.M. Research progress on anti-cancer mechanism of classical antibacterial chloroiodoquine.Zhongguo Xin Yao Zazhi2015240910021006
    [Google Scholar]
  79. WhiteM.C. JohnsonG.G. ZhangW. HobrathJ.V. PiazzaG.A. GrimaldiM. Sulindac sulfide inhibits sarcoendoplasmic reticulum Ca2+ ATPase, induces endoplasmic reticulum stress response, and exerts toxicity in glioma cells: Relevant similarities to and important differences from celecoxib.J. Neurosci. Res.201391339340610.1002/jnr.2316923280445
    [Google Scholar]
  80. VossJ.C. MahaneyJ.E. ThomasD.D. Mechanism of Ca-ATPase inhibition by melittin in skeletal sarcoplasmic reticulum.Biochemistry199534393093910.1021/bi00003a0277827051
    [Google Scholar]
  81. SenftD. RonaiZ.A. UPR, autophagy, and mitochondria crosstalk underlies the ER stress response.Trends Biochem. Sci.201540314114810.1016/j.tibs.2015.01.00225656104
    [Google Scholar]
  82. KroemerG. GalluzziL. BrennerC. Mitochondrial membrane permeabilization in cell death.Physiol. Rev.20078719916310.1152/physrev.00013.200617237344
    [Google Scholar]
  83. ChipukJ.E. GreenD.R. How do BCL-2 proteins induce mitochondrial outer membrane permeabilization?Trends Cell Biol.200818415716410.1016/j.tcb.2008.01.00718314333
    [Google Scholar]
  84. LiZ. ZhangR. YinX. LiN. CuiS. WangT. TanX. ShenM. GuoY. WangJ. GuoD. XuR. Realgar (As4S4), a traditional Chinese medicine, induces acute promyelocytic leukemia cell death via the Bcl-2/Bax/Cyt-C/AIF signaling pathway in vitro .Aging (Albany NY)202214177109712510.18632/aging.20428136098742
    [Google Scholar]
  85. ChenX. LiS. ZengZ. GuZ. YuY. zhengF. ZhouY. WangH. Notch1 signalling inhibits apoptosis of human dental follicle stem cells via both the cytoplasmic mitochondrial pathway and nuclear transcription regulation.Int. J. Biochem. Cell Biol.201782182710.1016/j.biocel.2016.11.01327888063
    [Google Scholar]
  86. SongM. ZhangJ. HuoS. ZhangX. CuiY. LiY. Mitophagy alleviates AIF-mediated spleen apoptosis induced by AlCl3 through Parkin stabilization in mice.Food Chem. Toxicol.202317611376210.1016/j.fct.2023.11376237028746
    [Google Scholar]
  87. ZongL. LiangZ. Apoptosis-inducing factor: A mitochondrial protein associated with metabolic diseases — A narrative review.Cardiovasc. Diagn. Ther.202312360962210.21037/cdt‑23‑12337405018
    [Google Scholar]
  88. ZhangJ. GuoJ. YangN. HuangY. HuT. RaoC. Endoplasmic reticulum stress-mediated cell death in liver injury.Cell Death Dis.20221312105110.1038/s41419‑022‑05444‑x36535923
    [Google Scholar]
  89. RakeshR. PriyaDharshiniL.C. SakthivelK.M. RasmiR.R. Role and regulation of autophagy in cancer.Biochim. Biophys. Acta Mol. Basis Dis.20221868716640010.1016/j.bbadis.2022.16640035341960
    [Google Scholar]
  90. Da Costa MacHadoA.K. MacHadoC.B. De Pinho PessoaF.M.C. BarretoI.V. GadelhaR.B. De Sousa OliveiraD. Monteiro RibeiroR. Silva LopesG. De Moraes FilhoM.O. Amaral De MoraesM.E. KhayatA.S. Moreira-NunesC.A. Development and clinical applications of PI3K/AKT/mTOR pathway inhibitors as a therapeutic option for leukemias.Cancer Diagn. Progn.20244192410.21873/cdp.1027938173664
    [Google Scholar]
  91. LiaoW.T. ChiangY.J. Yang-YenH.F. HsuL.C. ChangZ.F. YenJ.J.Y. Correction: CBAP regulates the function of Akt-associated TSC protein complexes to modulate mTORC1 signaling.J. Biol. Chem.2024300210568610.1016/j.jbc.2024.10568638290174
    [Google Scholar]
  92. HeZ. XuY. RaoZ. ZhangZ. ZhouJ. ZhouT. WangH. The role of α7-nAChR-mediated PI3K/AKT pathway in lung cancer induced by nicotine.Sci. Total Environ.202491216960410.1016/j.scitotenv.2023.16960438157907
    [Google Scholar]
  93. ChenL. ZhuL. ShiH. XieZ.Y. JiangZ.L. XuZ.Y. ZhangZ.J. WuX.T. Endoplasmic reticulum stress-mediated autophagy alleviates lipopolysaccharide-induced nucleus pulposus cell pyroptosis by inhibiting CHOP signaling in vitro .J. Biochem. Mol. Toxicol.2024381e2352310.1002/jbt.2352337654027
    [Google Scholar]
  94. KhezriM.R. HsuehH.Y. MohammadipanahS. Khalili FardJ. Ghasemnejad-BerenjiM. The interplay between the PI3K/AKT pathway and circadian clock in physiologic and cancer-related pathologic conditions.Cell Prolif.2024577e1360810.1111/cpr.1360838336976
    [Google Scholar]
  95. WisemanR.L. MesgarzadehJ.S. HendershotL.M. Reshaping endoplasmic reticulum quality control through the unfolded protein response.Mol. Cell20228281477149110.1016/j.molcel.2022.03.02535452616
    [Google Scholar]
  96. HuX. PanG. LuoJ. GaoX. MuY. WangZ. HuX. LiC. AbbasM.N. ZhangK. ZhengY. CuiH. Kuwanon H inhibits melanoma growth through cytotoxic endoplasmic reticulum stress and impaired autophagy flux.J. Agric. Food Chem.20237137137681378210.1021/acs.jafc.3c0225737672659
    [Google Scholar]
  97. GeY. ZhouM. ChenC. WuX. WangX. Role of AMPK mediated pathways in autophagy and aging.Biochimie202219510011310.1016/j.biochi.2021.11.00834838647
    [Google Scholar]
  98. MihaylovaM.M. ShawR.J. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism.Nat. Cell Biol.20111391016102310.1038/ncb232921892142
    [Google Scholar]
  99. HerzigS. ShawR.J. AMPK: Guardian of metabolism and mitochondrial homeostasis.Nat. Rev. Mol. Cell Biol.201819212113510.1038/nrm.2017.9528974774
    [Google Scholar]
  100. ZhangJ. YangL. HanX. LiC. LiuR. MaZ. HanB. XieR. YangQ. Endoplasmic reticulum stress in hepatic stellate cells induced by tunicamycin promotes apoptosis and cell cycle arrest.Xibao Yu Fenzi Mianyixue Zazhi202137979480034533126
    [Google Scholar]
  101. KhanM.G.M. WangY. Cell cycle-related clinical applications.Methods Mol. Biol.20222579354610.1007/978‑1‑0716‑2736‑5_336045196
    [Google Scholar]
  102. Heber-KatzE. ZhangY. BedelbaevaK. SongF. ChenX. StocumD.L. Cell cycle regulation and regeneration.Curr. Top. Microbiol. Immunol.201236725327610.1007/82_2012_29423263201
    [Google Scholar]
  103. KahlC.R. MeansA.R. Regulation of cell cycle progression by calcium/calmodulin-dependent pathways.Endocr. Rev.200324671973610.1210/er.2003‑000814671000
    [Google Scholar]
  104. HuangY. YangM. HuangW. 14-3-3 σ: A potential biomolecule for cancer therapy.Clin. Chim. Acta2020511505810.1016/j.cca.2020.09.00932950519
    [Google Scholar]
  105. BourougaaK. NaskiN. BoularanC. MlynarczykC. CandeiasM.M. MarulloS. FåhraeusR. Endoplasmic reticulum stress induces G2 cell-cycle arrest via mRNA translation of the p53 isoform p53/47.Mol. Cell2010381788810.1016/j.molcel.2010.01.04120385091
    [Google Scholar]
  106. AgarwalP. DeInnocentesP. BirdR.C. Evaluation of 14-3-3 sigma as a potential partner of p16 in quiescence and differentiation. in vitro Cell. Dev. Biol. Anim.201854965866510.1007/s11626‑018‑0291‑130168069
    [Google Scholar]
  107. ChanT.A. HermekingH. LengauerC. KinzlerK.W. VogelsteinB. 14-3-3σ is required to prevent mitotic catastrophe after DNA damage.Nature1999401675361662010.1038/4418810524633
    [Google Scholar]
/content/journals/cdt/10.2174/0113894501325497240918042654
Loading
/content/journals/cdt/10.2174/0113894501325497240918042654
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test