Skip to content
2000
Volume 17, Issue 1
  • ISSN: 1874-4672
  • E-ISSN: 1874-4702

Abstract

Background:

Lung cancer (LC) incidence is rising globally and is reflected as a leading cause of cancer-associated deaths. Lung cancer leads to multistage carcinogenesis with gradually increasing genetic and epigenetic changes.

Aims:

Sanguinarine (sang) mediated the anticancer effect in LCC lines by involving the stimulation of reactive oxygen species (ROS), impeding Bcl2, and enhancing Bax and other apoptosis-associated protein Caspase-3, -9, and -PARP, subsequently inhibiting the LC invasion and migration.

Objective:

This study was conducted to investigate the apoptotic rate and mechanism of Sang in human LC cells (LCC) H522 and H1299.

Methods:

MTT assay to determine the IC, cell morphology, and colony formation assay were carried out to show the sanguinarine effect on the LC cell line. Moreover, scratch assay and transwell assay were performed to check the migration. Western blotting and qPCR were done to show its effects on targeted proteins and genes. ELISA was performed to show the VEGF effect after Sanguinarine treatment. Immunofluorescence was done to check the interlocution of the targeted protein.

Results:

Sang significantly inhibited the growth of LCC lines in both time- and dose-dependent fashions. Flow cytometry examination and Annexin-V labeling determined that Sang increased the apoptotic cell percentage. H522 and H1299 LCC lines treated with Sang showed distinctive characteristics of apoptosis, including morphological changes and DNA fragmentation.

Conclusion:

Sang exhibited anticancer potential in LCC lines and could induce apoptosis and impede the invasion and migration of LCC, emerging as a promising anticancer natural agent in lung cancer management.

This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Loading

Article metrics loading...

/content/journals/cmp/10.2174/0118761429269383231119062233
2024-01-01
2024-11-26
Loading full text...

Full text loading...

/deliver/fulltext/cmp/17/1/BMS-CMP-2023-194.html?itemId=/content/journals/cmp/10.2174/0118761429269383231119062233&mimeType=html&fmt=ahah

References

  1. DuruisseauxM. EstellerM. Lung cancer epigenetics: From knowledge to applications.Semin. Cancer Biol.20185111612810.1016/j.semcancer.2017.09.00528919484
    [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. JemalA. MurrayT. WardE. SamuelsA. TiwariR.C. GhafoorA. FeuerE.J. ThunM.J. Cancer Statistics, 2005.CA Cancer J. Clin.2005551103010.3322/canjclin.55.1.1015661684
    [Google Scholar]
  4. JangB.C. ParkJ.G. SongD.K. BaekW.K. YooS.K. JungK.H. ParkG.Y. LeeT.Y. SuhS.I. Sanguinarine induces apoptosis in A549 human lung cancer cells primarily via cellular glutathione depletion.Toxicol. In Vitro200923228128710.1016/j.tiv.2008.12.01319135517
    [Google Scholar]
  5. KerrJ F R. WyllieA.H. CurrieA.R. Apoptosis: A basic biological phenomenon with wide-ranging implications in tissue kinetics.Br. J. Cancer197226423925710.1038/bjc.1972.334561027
    [Google Scholar]
  6. MariñoG. Niso-SantanoM. BaehreckeE.H. KroemerG. Self-consumption: The interplay of autophagy and apoptosis.Nat. Rev. Mol. Cell Biol.2014152819410.1038/nrm373524401948
    [Google Scholar]
  7. HengartnerM.O. Genetic control of programmed cell death and aging in the nematode Caenorhabditis elegans.Exp. Gerontol.1997324-536337410.1016/S0531‑5565(96)00167‑29315441
    [Google Scholar]
  8. FuchsY. StellerH. Programmed cell death in animal development and disease.Cell2011147474275810.1016/j.cell.2011.10.03322078876
    [Google Scholar]
  9. PanganibanR.A. SnowA. DayR. Mechanisms of radiation toxicity in transformed and non-transformed cells.Int. J. Mol. Sci.2013148159311595810.3390/ijms14081593123912235
    [Google Scholar]
  10. MortezaeeK. SalehiE. Mirtavoos-mahyariH. MotevaseliE. NajafiM. FarhoodB. RosengrenR.J. SahebkarA. Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy.J. Cell. Physiol.20192348125371255010.1002/jcp.2812230623450
    [Google Scholar]
  11. NajafiM. MotevaseliE. ShiraziA. GerailyG. RezaeyanA. NorouziF. RezapoorS. AbdollahiH. Mechanisms of inflammatory responses to radiation and normal tissues toxicity: Clinical implications.Int. J. Radiat. Biol.201894433535610.1080/09553002.2018.144009229504497
    [Google Scholar]
  12. BoldR.J. TermuhlenP.M. McConkeyD.J. Apoptosis, cancer and cancer therapy.Surg. Oncol.19976313314210.1016/S0960‑7404(97)00015‑79576629
    [Google Scholar]
  13. KoffJ. RamachandiranS. Bernal-MizrachiL. A time to kill: Targeting apoptosis in cancer.Int. J. Mol. Sci.20151622942295510.3390/ijms1602294225636036
    [Google Scholar]
  14. WangX. WeiL. CramerJ.M. LeibowitzB.J. JudgeC. EpperlyM. GreenbergerJ. WangF. LiL. StelznerM.G. DunnJ.C.Y. MartinM.G. LagasseE. ZhangL. YuJ. Pharmacologically blocking p53-dependent apoptosis protects intestinal stem cells and mice from radiation.Sci. Rep.201551856610.1038/srep0856625858503
    [Google Scholar]
  15. Balcer-KubiczekE.K. Apoptosis in radiation therapy: A double-edged sword.Exp. Oncol.201234327728523070013
    [Google Scholar]
  16. BrentnallM. Rodriguez-MenocalL. De GuevaraR.L. CeperoE. BoiseL.H. Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis.BMC Cell Biol.20131413210.1186/1471‑2121‑14‑3223834359
    [Google Scholar]
  17. IqbalH. RazzaqA. UzairB. Ul AinN. SajjadS. AlthobaitiN.A. AlbalawiA.E. MenaaB. HaroonM. KhanM. KhanN.U. MenaaF. Breast cancer inhibition by biosynthesized titanium dioxide nanoparticles is comparable to free doxorubicin but appeared safer in BALB/c mice.Materials20211412315510.3390/ma1412315534201266
    [Google Scholar]
  18. HanM.H. KimG.Y. YooY.H. ChoiY.H. Sanguinarine induces apoptosis in human colorectal cancer HCT-116 cells through ROS-mediated Egr-1 activation and mitochondrial dysfunction.Toxicol. Lett.2013220215716610.1016/j.toxlet.2013.04.02023660334
    [Google Scholar]
  19. PelicanoH. CarneyD. HuangP. ROS stress in cancer cells and therapeutic implications.Drug Resist. Updat.2004729711010.1016/j.drup.2004.01.00415158766
    [Google Scholar]
  20. KimI.H. KimS.W. KimS.H. LeeS.O. LeeS.T. KimD.G. LeeM.J. ParkW.H. Parthenolide-induced apoptosis of hepatic stellate cells and anti-fibrotic effects in an in vivo rat model.Exp. Mol. Med.201244744845610.3858/emm.2012.44.7.05122581380
    [Google Scholar]
  21. SusinS.A. ZamzamiN. KroemerG. Mitochondria as regulators of apoptosis: Doubt no more.Biochim. Biophys. Acta Bioenerg.199813661-215116510.1016/S0005‑2728(98)00110‑89714783
    [Google Scholar]
  22. IqbalH. MenaaF. KhanN.U. RazzaqA. KhanZ.U. UllahK. KamalR. SohailM. ThiripuranatharG. UzairB. RanaN.F. KhanB.A. MenaaB. Two promising anti-cancer compounds, 2-hydroxycinnaldehyde and 2- benzoyloxycinnamaldehyde: Where do we stand?Comb. Chem. High Throughput Screen.202225580881810.2174/138620732466621021609442833593253
    [Google Scholar]
  23. UllahA. LeongS.W. WangJ. WuQ. GhauriM.A. SarwarA. SuQ. ZhangY. Cephalomannine inhibits hypoxia-induced cellular function via the suppression of APEX1/HIF-1α interaction in lung cancer.Cell Death Dis.202112549010.1038/s41419‑021‑03771‑z33990544
    [Google Scholar]
  24. AminiP. Mirtavoos-MahyariH. MotevaseliE. ShabeebD. MusaA.E. ChekiM. FarhoodB. YahyapourR. ShiraziA. GoushbolaghN.A. NajafiM. Mechanisms for radioprotection by melatonin; can it be used as a radiation countermeasure?Curr. Mol. Pharmacol.201912121110.2174/187446721166618080216444930073934
    [Google Scholar]
  25. YahyapourR. ShabeebD. ChekiM. MusaA.E. FarhoodB. RezaeyanA. AminiP. FallahH. NajafiM. Radiation protection and mitigation by natural antioxidants and flavonoids: Implications to radiotherapy and radiation disasters.Curr. Mol. Pharmacol.201811428530410.2174/187446721166618061912565329921213
    [Google Scholar]
  26. MahadyG. BeecherC. Quercetin-induced benzophenanthridine alkaloid production in suspension cell cultures of Sanguinaria canadensis.Planta Med.199460655355710.1055/s‑2006‑9595707809211
    [Google Scholar]
  27. TandonR.K. SinghD.S. AroraR.R. LalP. TandonB.N. Epidemic dropsy in New Delhi.Am. J. Clin. Nutr.197528888388710.1093/ajcn/28.8.8831146749
    [Google Scholar]
  28. ZhangQ. LyuY. HuangJ. ZhangX. YuN. WenZ. ChenS. Antibacterial activity and mechanism of sanguinarine against Providencia rettgeri in vitro.PeerJ20208e954310.7717/peerj.954332864203
    [Google Scholar]
  29. FuC. GuanG. WangH. The anticancer effect of sanguinarine: A review.Curr. Pharm. Des.201824242760276410.2174/138161282466618082910060130156147
    [Google Scholar]
  30. AchkarI.W. MraicheF. MohammadR.M. UddinS. Anticancer potential of sanguinarine for various human malignancies.Future Med. Chem.20179993395010.4155/fmc‑2017‑004128636454
    [Google Scholar]
  31. SuQ. FanM. WangJ. UllahA. GhauriM.A. DaiB. ZhanY. ZhangD. ZhangY. Sanguinarine inhibits epithelial–mesenchymal transition via targeting HIF-1α/TGF-β feed-forward loop in hepatocellular carcinoma.Cell Death Dis.2019101293910.1038/s41419‑019‑2173‑131819036
    [Google Scholar]
  32. SuQ. WangJ. FanM. GhauriM.A. UllahA. WangB. DaiB. ZhanY. ZhangD. ZhangY. Sanguinarine disrupts the colocalization and interaction of HIF-1α with tyrosine and serine phosphorylated-STAT3 in breast cancer.J. Cell. Mol. Med.20202463756376110.1111/jcmm.1505632065498
    [Google Scholar]
  33. SuQ. WangJ. WuQ. UllahA. GhauriM.A. SarwarA. ChenL. LiuF. ZhangY. Sanguinarine combats hypoxia-induced activation of EphB4 and HIF-1α pathways in breast cancer.Phytomedicine20218415350310.1016/j.phymed.2021.15350333636580
    [Google Scholar]
  34. GhauriM.A. SuQ. UllahA. WangJ. SarwarA. WuQ. ZhangD. ZhangY. Sanguinarine impedes metastasis and causes inversion of epithelial to mesenchymal transition in breast cancer.Phytomedicine20218415350010.1016/j.phymed.2021.15350033626427
    [Google Scholar]
  35. WangJ. SuQ. WuQ. ChenK. UllahA. GhauriM.A. ZhangY. Sanguinarine impairs lysosomal function and induces ROS-dependent mitophagy and apoptosis in human hepatocellular carcinoma cells.Arch. Pharm. Res.202144111025103610.1007/s12272‑021‑01356‑034751932
    [Google Scholar]
  36. ShahS.L. BashirK. RasheedH.M. RahmanJ.U. IkramM. ShahA.J. MajrashiK.A. AlnasserS.M. MenaaF. KhanT. LC-MS/MS-based metabolomic profiling of constituents from glochidion velutinum and its activity against cancer cell lines.Molecules20222724901210.3390/molecules2724901236558144
    [Google Scholar]
  37. WangH. RaoB. LouJ. LiJ. LiuZ. LiA. CuiG. RenZ. YuZ. The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma.Front. Cell Dev. Biol.202085510.3389/fcell.2020.0005532117981
    [Google Scholar]
  38. WangH. CuiH. YangX. PengL. TUBA1C: A new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression.BMC Cancer202323125810.1186/s12885‑023‑10707‑736941595
    [Google Scholar]
  39. XieF. ZhuH. ZhangH. LangQ. TangL. HuangQ. YuL. In vitro and in vivo characterization of a benzofuran derivative, a potential anticancer agent, as a novel Aurora B kinase inhibitor.Eur. J. Med. Chem.20158931031910.1016/j.ejmech.2014.10.04425462247
    [Google Scholar]
  40. YanW. MaX. ZhaoX. ZhangS. Baicalein induces apoptosis and autophagy of breast cancer cells via inhibiting PI3K/AKT pathway in vivo and vitro.Drug Des. Devel. Ther.2018123961397210.2147/DDDT.S18193930510404
    [Google Scholar]
  41. SumnerG. GeorgarosC. RafiqueA. DiCioccioT. MartinJ. PapadopoulosN. DalyT. TorriA. Anti-VEGF drug interference with VEGF quantitation in the R&D systems human quantikine VEGF ELISA kit.Bioanalysis201911538139210.4155/bio‑2018‑009630892063
    [Google Scholar]
  42. KuoC.T. ChenC.L. LiC.C. HuangG.S. MaW.Y. HsuW.F. LinC.H. LuY.S. WoA.M. Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models.Sci. Rep.2019911089810.1038/s41598‑019‑45319‑431358767
    [Google Scholar]
  43. HuangC. KohnoN. InufusaH. KodamaK. TakiT. MiyakeM. Overexpression of bax associated with mutations in the loop-sheet-helix motif of p53.Am. J. Pathol.1999155395596510.1016/S0002‑9440(10)65195‑410487853
    [Google Scholar]
  44. GongQ. LiuC. WangC. ZhuangL. ZhangL. WangX. Effect of silencing TEM8 gene on proliferation, apoptosis, migration and invasion of XWLC‑05 lung cancer cells.Mol. Med. Rep.20181791191729115620
    [Google Scholar]
  45. FolkmanJ. Angiogenesis and apoptosis.Semin. Cancer Biol.200313215916710.1016/S1044‑579X(02)00133‑512654259
    [Google Scholar]
  46. ZhaoQ. ZhangB. LiZ. TangW. DuL. SangH. Effects of IncRNA PROX1-AS1 on proliferation, migration, invasion and apoptosis of lung cancer cells by regulating MiR-1305.J. Healthc. Eng.202220221910.1155/2022/957090035281529
    [Google Scholar]
  47. KoJ. WinslowM.M. SageJ. Mechanisms of small cell lung cancer metastasis.EMBO Mol. Med.2021131e1312210.15252/emmm.20201312233296145
    [Google Scholar]
  48. AlbuquerqueC. ManguinhasR. CostaJ.G. GilN. Codony-ServatJ. CastroM. MirandaJ.P. FernandesA.S. RosellR. OliveiraN.G. A narrative review of the migration and invasion features of non-small cell lung cancer cells upon xenobiotic exposure: insights from in vitro studies.Transl. Lung Cancer Res.20211062698271410.21037/tlcr‑21‑12134295671
    [Google Scholar]
  49. Gomez-LarrauriA. OuroA. TruebaM. Gomez-MuñozA. Regulation of cell growth, survival and migration by ceramide 1-phosphate - implications in lung cancer progression and inflammation.Cell. Signal.20218310998010.1016/j.cellsig.2021.10998033727076
    [Google Scholar]
  50. FeitelsonM.A. ArzumanyanA. KulathinalR.J. BlainS.W. HolcombeR.F. MahajnaJ. MarinoM. Martinez-ChantarM.L. NawrothR. Sanchez-GarciaI. SharmaD. SaxenaN. K. SinghN. VlachostergiosP.J. GuoS. HonokiK. FujiiH. GeorgakilasA.G. BilslandA. AmedeiA. NiccolaiE. AminA. AshrafS.S. BoosaniC.S. GuhaG. CirioloM.R. AquilanoK. ChenS. MohammedS.I. AzmiA.S. BhaktaD. HalickaD. KeithW.N. NowsheenS. Sustained proliferation in cancer: Mechanisms and novel therapeutic targets.Seminars in can-cer biology201535S25S54
    [Google Scholar]
  51. KlaunigJ.E. Oxidative stress and cancer.Curr. Pharm. Des.201924404771477810.2174/138161282566619021512171230767733
    [Google Scholar]
  52. ZhuY. XieN. ChaiY. NieY. LiuK. LiuY. YangY. SuJ. ZhangC. Apoptosis induction, a sharp edge of berberine to exert anti-cancer effects, focus on breast, lung, and liver cancer.Front. Pharmacol.20221380371710.3389/fphar.2022.80371735153781
    [Google Scholar]
  53. NishiharaS. YamaokaT. IshikawaF. HiguchiK. HasebeY. ManabeR. KishinoY. KusumotoS. AndoK. KurodaY. OhmoriT. SagaraH. YoshidaH. TsurutaniJ. Mechanisms of EGFR-TKI-induced apoptosis and strategies targeting apoptosis in EGFR-mutated non-small cell lung cancer.Genes20221312218310.3390/genes1312218336553449
    [Google Scholar]
  54. XuL. HuangX. LouY. XieW. ZhaoH. Regulation of apoptosis, autophagy and ferroptosis by non‑coding RNAs in metastatic non‑small cell lung cancer (Review).Exp. Ther. Med.202223535210.3892/etm.2022.1127935493430
    [Google Scholar]
  55. GongJ. SalgiaR. Managing patients with relapsed small-cell lung cancer.J. Oncol. Pract.201814635936610.1200/JOP.18.0020429894664
    [Google Scholar]
  56. QiF. ZhaoL. ZhouA. ZhangB. LiA. WangZ. HanJ. The advantages of using traditional Chinese medicine as an adjunctive therapy in the whole course of cancer treatment instead of only terminal stage of cancer.Biosci. Trends201591163410.5582/bst.2015.0101925787906
    [Google Scholar]
  57. UllahA. AzizT. UllahN. NawazT. Molecular mechanisms of Sanguinarine in cancer prevention and treatment.Anticancer. Agents Med. Chem.202323776577810.2174/187152062266622083112432136045531
    [Google Scholar]
  58. CroakerA. KingG. PyneJ. Anoopkumar-DukieS. LiuL. Sanguinaria canadensis: Traditional medicine, phytochemical composition, biological activities and current uses.Int. J. Mol. Sci.2016179141410.3390/ijms1709141427618894
    [Google Scholar]
  59. ObengE. Apoptosis (programmed cell death) and its signals - A review.Braz. J. Biol.20218141133114310.1590/1519‑6984.22843733111928
    [Google Scholar]
  60. LichanC. YanyunZ. Shu-FengZ. Role of apoptosis in cancer resistance to chemotherapy.In Current Understanding of Apoptosis YusufT. IntechOpenRijeka2018
    [Google Scholar]
  61. LiuL. FanJ. AiG. LiuJ. LuoN. LiC. ChengZ. Berberine in combination with cisplatin induces necroptosis and apoptosis in ovarian cancer cells.Biol. Res.20195213710.1186/s40659‑019‑0243‑631319879
    [Google Scholar]
  62. ChoiW.Y. KimG.Y. LeeW.H. ChoiY.H. Sanguinarine, a benzophenanthridine alkaloid, induces apoptosis in MDA-MB-231 human breast carcinoma cells through a reactive oxygen species-mediated mitochondrial pathway.Chemotherapy200854427928710.1159/00014971918667818
    [Google Scholar]
/content/journals/cmp/10.2174/0118761429269383231119062233
Loading
/content/journals/cmp/10.2174/0118761429269383231119062233
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keyword(s): Apoptosis; Cytometry; Flow; Lung cancer; Reactive oxygen species; Sanguinarine; Vegf
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