Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Recent Advances in Drug Delivery and Formulation
  4. Volume 18, Issue 4
  5. Article
Volume 18, Issue 4
  • ISSN: 2667-3878
  • E-ISSN: 2667-3886

Abstract

Background

Autophagy plays a crucial role in modulating the proliferation of cancer diseases. However, the application of Naringenin (Nar), a compound with potential benefits against these diseases, has been limited due to its poor solubility and bioavailability.

Objective

This study aimed to develop solid lipid nanoparticles (Nar-SLNs) loaded with Nar to enhance their therapeutic impact.

Methods

experiments using Rin-5F cells exposed to Nar and Nar-SLNs were carried out to investigate the protective effects of Nar and its nanoformulation against the pancreatic cancer cell line of Rin-5F.

Results

Treatment with Nar and Nar-SLN led to an increase in autophagic markers (Akt, LC3, Beclin1, and ATG genes) and a decrease in the level of miR-21. Both Nar and Nar-SLN treatments inhibited cell proliferation and reduced the expression of autophagic markers. Notably, Nar-SLNs exhibited greater efficacy compared to free Nar.

Conclusion

These findings suggest that SLNs effectively enhance the cytotoxic impact of Nar, making Nar-SLNs a promising candidate for suppressing or preventing Rin-5F cell growth.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/raddf/10.2174/0126673878297658240804192222
2024-12-01
2025-06-23

  • From This Site

    /content/journals/raddf/10.2174/0126673878297658240804192222
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. OwensD.K. DavidsonK.W. KristA.H. Screening for pancreatic cancer: US preventive services task force reaffirmation recommendation statement.JAMA2019322543844410.1001/jama.2019.10232 31386141
     [Google Scholar]
  2. LuoW. TaoJ. ZhengL. ZhangT. Current epidemiology of pancreatic cancer: Challenges and opportunities.Chin. J. Cancer Res.202032670571910.21147/j.issn.1000‑9604.2020.06.04 33446994
     [Google Scholar]
  3. JagadeesanB. HaranP.H. PraveenD. ChowdaryP.R. AanandhiM.V. A comprehensive review on pancreatic cancer.Res J Pharm Technol202114155255410.5958/0974‑360X.2021.00100.1
     [Google Scholar]
  4. HuJ.X. ZhaoC.F. ChenW.B. Pancreatic cancer: A review of epidemiology, trend, and risk factors.World J. Gastroenterol.202127274298432110.3748/wjg.v27.i27.4298 34366606
     [Google Scholar]
  5. ChengJin LingBai Pancreatic cancer: Current situation and challenges.Gastroenterol Hepatol Lett2020211310.18063/ghl.v2i1.243
     [Google Scholar]
  6. MeniniS. IacobiniC. VitaleM. PesceC. PuglieseG. Diabetes and pancreatic cancer—A dangerous liaison relying on carbonyl stress.Cancers202113231310.3390/cancers13020313 33467038
     [Google Scholar]
  7. LiangJ.Q. TeohN. XuL. Dietary cholesterol promotes steatohepatitis related hepatocellular carcinoma through dysregulated metabolism and calcium signaling.Nat. Commun.201891449010.1038/s41467‑018‑06931‑6 30367044
     [Google Scholar]
  8. KlionskyD.J. EmrS.D. Autophagy as a regulated pathway of cellular degradation.Science200029054971717172110.1126/science.290.5497.1717 11099404
     [Google Scholar]
  9. EbatoC. UchidaT. ArakawaM. Autophagy is important in islet homeostasis and compensatory increase of beta cell mass in response to high-fat diet.Cell Metab.20088432533210.1016/j.cmet.2008.08.009 18840363
     [Google Scholar]
  10. BoyaP González-Polo RA, Casares N, et al. Inhibition of macroautophagy triggers apoptosis.Mol. Cell. Biol.20052531025104010.1128/MCB.25.3.1025‑1040.2005 15657430
     [Google Scholar]
  11. TsujimotoY. ShimizuS. Another way to die: Autophagic programmed cell death.Cell Death Differ.200512Suppl. 21528153410.1038/sj.cdd.4401777 16247500
     [Google Scholar]
  12. EltschingerS. LoewithR. TOR complexes and the maintenance of cellular homeostasis.Trends Cell Biol.201626214815910.1016/j.tcb.2015.10.003 26546292
     [Google Scholar]
  13. LevineB. KroemerG. SnapShot: Macroautophagy.Cell Death Differ.2008132116210.1016/j.cell.2007.12.026
     [Google Scholar]
  14. LimY.M. LimH. HurK.Y. Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes.Nat. Commun.201451493410.1038/ncomms5934 25255859
     [Google Scholar]
  15. ShibataM. YoshimuraK. FuruyaN. The MAP1-LC3 conjugation system is involved in lipid droplet formation.Biochem. Biophys. Res. Commun.2009382241942310.1016/j.bbrc.2009.03.039 19285958
     [Google Scholar]
  16. SinghJ.A. SaagK.G. BridgesS.L.Jr 2015 American college of rheumatology guideline for the treatment of rheumatoid arthritis.Arthritis Rheumatol.201668112610.1002/art.39480 26545940
     [Google Scholar]
  17. ZhangY. GoldmanS. BaergaR. ZhaoY. KomatsuM. JinS. Adipose-specific deletion of autophagy-related gene 7 (atg7) in mice reveals a role in adipogenesis.Proc. Natl. Acad. Sci. USA200910647198601986510.1073/pnas.0906048106 19910529
     [Google Scholar]
  18. DeshpandeS. AbdollahiM. WangM. LantingL. KatoM. NatarajanR. Reduced autophagy by a microRNA-mediated signaling cascade in diabetes-induced renal glomerular hypertrophy.Sci. Rep.201881695410.1038/s41598‑018‑25295‑x 29725042
     [Google Scholar]
  19. EstrellaS. Garcia-DiazD.F. CodnerE. Camacho-GuillénP. Pérez-BravoF. Expression of miR-22 and miR-150 in type 1 diabetes mellitus: Possible relationship with autoimmunity and clinical characteristics.J Medicina Clínica20161476245247 27377214
     [Google Scholar]
  20. MadhyasthaR. MadhyasthaH. NakajimaY. OmuraS. MaruyamaM. MicroRNA signature in diabetic wound healing: Promotive role of miR‐21 in fibroblast migration.Int. Wound J.20129435536110.1111/j.1742‑481X.2011.00890.x 22067035
     [Google Scholar]
  21. OlivieriF. SpazzafumoL. BonafèM. MiR-21-5p and miR-126a-3p levels in plasma and circulating angiogenic cells: Relationship with type 2 diabetes complications.Oncotarget20156343537235382 26498351
     [Google Scholar]
  22. ZhongX. ChungA.C.K. ChenH.Y. miR-21 is a key therapeutic target for renal injury in a mouse model of type 2 diabetes.Diabetologia201356366367410.1007/s00125‑012‑2804‑x 23292313
     [Google Scholar]
  23. GuoY.B. JiT.F. ZhouH.W. YuJ.L. Retracted article: Effects of microRNA-21 on nerve cell regeneration and neural function recovery in diabetes mellitus combined with cerebral infarction rats by targeting pdcd4.Mol. Neurobiol.20185532494250510.1007/s12035‑017‑0484‑8 28389999
     [Google Scholar]
  24. ZhangY. MicroRNA-22 promotes renal tubulointerstitial fibrosis by targeting PTEN and suppressing autophagy in diabetic nephropathy.J. Diabetes Res.201820184728645
     [Google Scholar]
  25. ChenZ. LiY.B. HanJ. The double-edged effect of autophagy in pancreatic beta cells and diabetes.Autophagy201171121610.4161/auto.7.1.13607 20935505
     [Google Scholar]
  26. YangL.C. HsiehC.C. WenC.L. ChiuC.H. LinW.C. Structural characterization of an immunostimulating polysaccharide from the stems of a new medicinal Dendrobium species: Dendrobium Taiseed Tosnobile.Int. J. Biol. Macromol.20171031185119310.1016/j.ijbiomac.2017.05.185 28579460
     [Google Scholar]
  27. HidayatA.F.A. ChanC.K. MohamadJ. KadirH.A. Leptospermum flavescens Sm. Protect pancreatic β cell function from streptozotocin involving apoptosis and autophagy signaling pathway in in vitro and in vivo case study.J. Ethnopharmacol.201822612013110.1016/j.jep.2018.08.020 30118836
     [Google Scholar]
  28. VarshneyR. GuptaS. RoyP. Cytoprotective effect of kaempferol against palmitic acid-induced pancreatic β-cell death through modulation of autophagy via AMPK/mTOR signaling pathway.Mol. Cell. Endocrinol.201744812010.1016/j.mce.2017.02.033 28237721
     [Google Scholar]
  29. FattahiA. NiyaziF. ShahbaziB. FarzaeiM.H. BahramiG. Antidiabetic mechanisms of Rosa canina fruits: An in vitro evaluation.J. Evid. Based Complementary Altern. Med.201722112713310.1177/2156587216655263 27352916
     [Google Scholar]
  30. NouriZ. FakhriS. El-SendunyF.F. On the neuroprotective effects of naringenin: Pharmacological targets, signaling pathways, molecular mechanisms, and clinical perspective.Biomolecules201991169010.3390/biom9110690 31684142
     [Google Scholar]
  31. NouriZ. HajialyaniM. IzadiZ. BahramsoltaniR. FarzaeiM.H. AbdollahiM. Nanophytomedicines for the prevention of metabolic syndrome: A pharmacological and biopharmaceutical review.Front. Bioeng. Biotechnol.2020842510.3389/fbioe.2020.00425 32478050
     [Google Scholar]
  32. MishraV. BansalK.K. VermaA. Solid lipid nanoparticles: Emerging colloidal nano drug delivery systems.Pharmaceutics201810419110.3390/pharmaceutics10040191 30340327
     [Google Scholar]
  33. JiP. YuT. LiuY. Naringenin-loaded solid lipid nanoparticles: Preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics.Drug Des. Devel. Ther.201610911925 27041995
     [Google Scholar]
  34. NouriZ. SajadimajdS. HoseinzadehL. Neuroprotective effect of naringenin‐loaded solid lipid nanoparticles against streptozocin‐induced neurotoxicity through autophagy blockage.J. Food Biochem.20224612e1440810.1111/jfbc.14408 36129161
     [Google Scholar]
  35. AhmadifardZ. AhmedaA. RasekhianM. MoradiS. ArkanE. Chitosan-coated magnetic solid lipid nanoparticles for controlled release of letrozole.J. Drug Deliv. Sci. Technol.20205710162110.1016/j.jddst.2020.101621
     [Google Scholar]
  36. SajadimajdS. BahramiG. MohammadiB. NouriZ. FarzaeiM.H. ChenJ.T. Protective effect of the isolated oligosaccharide from Rosa canina in STZ‐treated cells through modulation of the autophagy pathway.J. Food Biochem.20204410e1340410.1111/jfbc.13404 32761921
     [Google Scholar]
  37. VisticaD.T. SkehanP. ScudieroD. MonksA. PittmanA. BoydM.R. Tetrazolium-based assays for cellular viability: A critical examination of selected parameters affecting formazan production.Cancer Res.1991511025152520 2021931
     [Google Scholar]
  38. LivakK.J. SchmittgenT.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) method.Methods200125440240810.1006/meth.2001.1262 11846609
     [Google Scholar]
  39. HashemiM. MirdamadiM.S.A. TalebiY. Pre-clinical and clinical importance of miR-21 in human cancers: Tumorigenesis, therapy response, delivery approaches and targeting agents.Pharmacol. Res.202318710656810.1016/j.phrs.2022.106568 36423787
     [Google Scholar]
  40. ZhaoQ. ChenS. ZhuZ. miR-21 promotes EGF-induced pancreatic cancer cell proliferation by targeting Spry2.Cell Death Dis.2018912115710.1038/s41419‑018‑1182‑9 30464258
     [Google Scholar]
  41. SuiX. ChenR. WangZ. Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment.Cell Death Dis.2013410e838810.1038/cddis.2013.350 24113172
     [Google Scholar]
  42. TraceyN. CreedonH. KempA.J. HO-1 drives autophagy as a mechanism of resistance against HER2-targeted therapies.Breast Cancer Res. Treat.2020179354355510.1007/s10549‑019‑05489‑1 31705351
     [Google Scholar]
  43. ClarkC.A. GuptaH.B. CurielT.J. Tumor cell-intrinsic CD274/PD-L1: A novel metabolic balancing act with clinical potential.Autophagy201713598798810.1080/15548627.2017.1280223 28368722
     [Google Scholar]
  44. QuX. YuJ. BhagatG. Promotion of tumorigenesis by heterozygous disruption of the beclin 1 autophagy gene.J. Clin. Invest.2003112121809182010.1172/JCI20039 14638851
     [Google Scholar]
  45. YueZ. JinS. YangC. LevineA.J. HeintzN. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.Proc. Natl. Acad. Sci. USA200310025150771508210.1073/pnas.2436255100 14657337
     [Google Scholar]
  46. TakamuraA. KomatsuM. HaraT. Autophagy-deficient mice develop multiple liver tumors.Genes Dev.201125879580010.1101/gad.2016211 21498569
     [Google Scholar]
  47. JungY.Y. LeeY.K. KooJ.S. The potential of Beclin 1 as a therapeutic target for the treatment of breast cancer.Expert Opin. Ther. Targets201620216717810.1517/14728222.2016.1085971 26357854
     [Google Scholar]
  48. YangS. WangX. ContinoG. Pancreatic cancers require autophagy for tumor growth.Genes Dev.201125771772910.1101/gad.2016111 21406549
     [Google Scholar]
  49. AlgulD. DumanG. OzdemirS. AcarE.T. YenerG. Preformulation, characterization, and in vitro release studies of caffeine-loaded solid lipid nanoparticles.J. Cosmet. Sci.2018693165173 30052191
     [Google Scholar]
  50. HuF. HongY. YuanH. Preparation and characterization of solid lipid nanoparticles containing peptide.Int. J. Pharm.20042731-2293510.1016/j.ijpharm.2003.12.016 15010127
     [Google Scholar]
  51. BollimpelliV.S. KumarP. KumariS. KondapiA.K. Neuroprotective effect of curcumin-loaded lactoferrin nano particles against rotenone induced neurotoxicity.Neurochem. Int.201695374510.1016/j.neuint.2016.01.006 26826319
     [Google Scholar]
  52. BrunetA. BonniA. ZigmondM.J. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor.Cell199996685786810.1016/S0092‑8674(00)80595‑4 10102273
     [Google Scholar]
  53. JohnA. RazaH. Azadirachtin attenuates lipopolysaccharide-induced ROS production, DNA damage, and apoptosis by regulating JNK/Akt and AMPK/mTOR-dependent pathways in Rin-5F pancreatic beta cells.Biomedicines20219121943 34944759
     [Google Scholar]
  54. HuoD. JiangS. QinZ. Omethoate induces pharyngeal cancer cell proliferation and G1/S cell cycle progression by activation of Akt/GSK-3β/cyclin D1 signaling pathway.Toxicology201942715229810.1016/j.tox.2019.152298 31574243
     [Google Scholar]
  55. MartindaleJ.L. HolbrookN.J. Cellular response to oxidative stress: Signaling for suicide and survival.J. Cell. Physiol.2002192111510.1002/jcp.10119 12115731
     [Google Scholar]
  56. JiangP. MizushimaN. Autophagy and human diseases.Cell Res.2014241697910.1038/cr.2013.161 24323045
     [Google Scholar]
  57. OrnatowskiW. LuQ. YegambaramM. Complex interplay between autophagy and oxidative stress in the development of pulmonary disease.Redox Biol.20203610167910.1016/j.redox.2020.101679 32818797
     [Google Scholar]
  58. ChenX. LiL. XuS. Ultraviolet B radiation down-regulates ULK1 and ATG7 expression and impairs the autophagy response in human keratinocytes.J. Photochem. Photobiol. B201817815216410.1016/j.jphotobiol.2017.08.043 29154199
     [Google Scholar]
  59. Madrigal-MatuteJ. CuervoA.M. Regulation of liver metabolism by autophagy.Gastroenterology2016150232833910.1053/j.gastro.2015.09.042 26453774
     [Google Scholar]
  60. YangY. FiskusW. YongB. Acetylated hsp70 and KAP1-mediated Vps34 SUMOylation is required for autophagosome creation in autophagy.Proc. Natl. Acad. Sci. USA2013110176841684610.1073/pnas.1217692110 23569248
     [Google Scholar]
  61. YangK. CaoF. WangW. TianZ. YangL. The relationship between HMGB1 and autophagy in the pathogenesis of diabetes and its complications.Front. Endocrinol.202314114151610.3389/fendo.2023.1141516 37065747
     [Google Scholar]
  62. EssickE.E. SamF. Oxidative stress and autophagy in cardiac disease, neurological disorders, aging and cancer.Oxid. Med. Cell. Longev.20103316817710.4161/oxim.3.3.12106 20716941
     [Google Scholar]
  63. BrimsonJ.M. PrasanthM.I. MalarD.S. Plant polyphenols for aging health: Implication from their autophagy modulating properties in age-associated diseases.Pharmaceuticals2021141098210.3390/ph14100982 34681206
     [Google Scholar]
  64. WangZ. QuanW. ZengM. Regulation of autophagy by plant‐based polyphenols: A critical review of current advances in glucolipid metabolic diseases and food industry applications.Food Front.2023431039106710.1002/fft2.255
     [Google Scholar]
  65. BarthS. GlickD. MacleodK.F. Autophagy: Assays and artifacts.J. Pathol.2010221211712410.1002/path.2694 20225337
     [Google Scholar]
  66. HsuC.P. OkaS. ShaoD. HariharanN. SadoshimaJ. Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes.Circ. Res.2009105548149110.1161/CIRCRESAHA.109.203703 19661458
     [Google Scholar]
  67. SalminenA. KaarnirantaK. SIRT1: Regulation of longevity via autophagy.Cell. Signal.20092191356136010.1016/j.cellsig.2009.02.014 19249351
     [Google Scholar]
  68. MaguraJ. HassanD. MoodleyR. MackrajI. Hesperidin-loaded nanoemulsions improve cytotoxicity, induce apoptosis, and downregulate miR-21 and miR-155 expression in MCF-7.J. Microencapsul.2021387-848649510.1080/02652048.2021.1979673 34510994
     [Google Scholar]
  69. FahmyA.M. LabontéP. The autophagy elongation complex (ATG5-12/16L1) positively regulates HCV replication and is required for wild-type membranous web formation.Sci. Rep.2017714035110.1038/srep40351 28067309
     [Google Scholar]
  70. ChenJ. ZhangL. ZhouH. Inhibition of autophagy promotes cisplatin-induced apoptotic cell death through Atg5 and Beclin 1 in A549 human lung cancer cells.Mol. Med. Rep.20181756859686510.3892/mmr.2018.8686 29512762
     [Google Scholar]
  71. UstunerD. KolacU.K. UstunerM.C. Naringenin ameliorate carbon tetrachloride-induced hepatic damage through inhibition of endoplasmic reticulum stress and autophagy in rats.J. Med. Food202023111192120010.1089/jmf.2019.0265 32125927
     [Google Scholar]
  72. XuZ. HanX. OuD. Targeting PI3K/AKT/mTOR-mediated autophagy for tumor therapy.Appl. Microbiol. Biotechnol.2020104257558710.1007/s00253‑019‑10257‑8 31832711
     [Google Scholar]
  73. WangX. JiangY. ZhuL. Autophagy protects PC12 cells against deoxynivalenol toxicity via the class III PI3K/beclin 1/Bcl‐2 pathway.J. Cell. Physiol.2020235117803781510.1002/jcp.29433 31930515
     [Google Scholar]
  74. XuL. ShenJ. YuL. Role of autophagy in sevoflurane-induced neurotoxicity in neonatal rat hippocampal cells.Brain Res. Bull.201814029129810.1016/j.brainresbull.2018.05.020 29857124
     [Google Scholar]
  75. Eisenberg-LernerA. BialikS. SimonH-U. KimchiA. Life and death partners: Apoptosis, autophagy and the cross-talk between them.Cell Death Differ.200916796697510.1038/cdd.2009.33 19325568
     [Google Scholar]
  76. GaoY. LiJ. WuL. Tetrahydrocurcumin provides neuroprotection in rats after traumatic brain injury: Autophagy and the PI3K/AKT pathways as a potential mechanism.J. Surg. Res.20162061677610.1016/j.jss.2016.07.014 27916377
     [Google Scholar]
  77. LiY. ChoM.H. LeeS.S. LeeD.E. CheongH. ChoiY. Hydroxychloroquine-loaded hollow mesoporous silica nanoparticles for enhanced autophagy inhibition and radiation therapy.J. Control. Release202032510011010.1016/j.jconrel.2020.06.025 32621826
     [Google Scholar]
  78. BaiY. SuX. PiaoL. JinZ. JinR. Involvement of astrocytes and microRNA dysregulation in neurodegenerative diseases: From pathogenesis to therapeutic potential.Front. Mol. Neurosci.20211455621510.3389/fnmol.2021.556215 33815055
     [Google Scholar]
  79. YuX. LiR. ShiW. Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells.Biomed. Pharmacother.201677374410.1016/j.biopha.2015.11.005 26796263
     [Google Scholar]
  80. MengX. ZhangY. HuangX.R. RenG. LiJ. LanH.Y. Treatment of renal fibrosis by rebalancing TGF-β/Smad signaling with the combination of asiatic acid and naringenin.Oncotarget2015635369843699710.18632/oncotarget.6100 26474462
     [Google Scholar]
  81. ShiL.B. TangP.F. ZhangW. ZhaoY.P. ZhangL.C. ZhangH. Naringenin inhibits spinal cord injury-induced activation of neutrophils through miR-223.Gene2016592112813310.1016/j.gene.2016.07.037 27432064
     [Google Scholar]
/content/journals/raddf/10.2174/0126673878297658240804192222
Loading
Cytotoxic Impact of Naringenin-Loaded Solid Lipid Nanoparticles on RIN5F Pancreatic β Cells via Autophagy Blockage
Recent Advances in Drug Delivery and Formulation 18, 304 (2024); https://doi.org/10.2174/0126673878297658240804192222
/content/journals/raddf/10.2174/0126673878297658240804192222
/content/journals/raddf/10.2174/0126673878297658240804192222
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): Autophagy; DNA mutations; miRNA; naringenin-loaded solid lipid nanoparticle; pancreatic cancer; Rin-5F cells

Most Cited Most Cited RSS feed

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