Skip to content
2000
Volume 12, Issue 1
  • ISSN: 2215-0838
  • E-ISSN: 2215-0846
file format text download EPUB
file format pdf download PDF
side by side viewer icon HTML

Abstract

Objective

Cancer is one of the major public health challenges globally and the second cause of death in developed countries. Studies have shown that natural products can be effective in treating cancer. The present study was conducted on the cytotoxicity and apoptogenic effects of stylosin on the HepG2 and U87 cell lines.

Materials and Methods

First, the cytotoxicity effect of stylosin was investigated using the MTT method. Also, the production of reactive oxygen species was measured. The amount of cell apoptosis was determined by the Sub G1 Peak method. Finally, to investigate the cellular and molecular mechanisms involved in stylosin toxicity, the expression of P53, BAX, Bcl-2, Caspase 3, Caspase 9, and p53 genes were evaluated by the RT-PCR method.

Results

Stylosin causes cytotoxicity in HepG2 and U87 cells in a time and concentration-dependent pattern. It also significantly increases ROS production and stimulates apoptosis. It induced a substantial enhancement in the expression of BAX, caspase3, and Caspase9 genes in HepG2 while decreasing Bcl-2 production and up-regulation of Caspase 3, Caspase 9, and p53 in U87 cells.

Discussion

The current study discusses the cytotoxic effects of stylosin on U87 and HepG2 cell lines. The findings revealed the effects of stylosin in increasing the cell death elevation of free radicals, apoptotic cells, and increased Bax, caspase3, and caspase 9. Cancer treatment poses as an important issue, especially for researchers and therapists. HCC is the most common type of liver cancer, which was identified because of its progressiveness, lethality, and resistance to common cancer therapies.

Conclusion

It is concluded that Stylosin can probably inhibit the proliferation of the cancer cell line by affecting the expression of genes involved in apoptosis and the production of ROS.

© 2026 The Author(s). Published by Bentham Science Publishers.
This is an open access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode
Loading

Article metrics loading...

/content/journals/ctm/10.2174/0122150838313458240524054119
2024-06-27
2026-01-03

  • From This Site

    /content/journals/ctm/10.2174/0122150838313458240524054119
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

/deliver/fulltext/ctm/12/1/CTM-12-E270624231396.html?itemId=/content/journals/ctm/10.2174/0122150838313458240524054119&mimeType=html&fmt=ahah

References

  1. FarhoodB. GerailyG. AlizadehA. Incidence and mortality of various cancers in Iran and compare to other countries: A review article.Iran. J. Public Health201847330931629845017
     [Google Scholar]
  2. BrayF. FerlayJ. SoerjomataramI. SiegelR. TorreL. JemalF. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.2018686394424
     [Google Scholar]
  3. ChenW. SunK. ZhengR. Cancer incidence and mortality in China, 2014.Chin. J. Cancer Res.201830111210.21147/j.issn.1000‑9604.2018.01.0129545714
     [Google Scholar]
  4. SungH. FerlayJ. SiegelR.L. 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]
  5. WenN. CaiY. LiF. The clinical management of hepatocellular carcinoma worldwide: A concise review and comparison of current guidelines: 2022 update.Biosci. Trends2022161203010.5582/bst.2022.0106135197399
     [Google Scholar]
  6. McGlynnK.A. PetrickJ.L. El-SeragH.B. Epidemiology of hepatocellular carcinoma.Hepatology202173S141310.1002/hep.3128832319693
     [Google Scholar]
  7. MareelM. LeroyA. Clinical, cellular, and molecular aspects of cancer invasion.Physiol. Rev.200383233737610.1152/physrev.00024.200212663862
     [Google Scholar]
  8. CampbellC. WangT. McNaughtonA.L. BarnesE. MatthewsP.C. Risk factors for the development of hepatocellular carcinoma (HCC) in chronic hepatitis B virus (HBV) infection: A systematic review and meta‐analysis.J. Viral Hepat.202128349350710.1111/jvh.1345233305479
     [Google Scholar]
  9. Ramos-TovarE. MurielP. Molecular mechanisms that link oxidative stress, inflammation, and fibrosis in the liver.Antioxidants2020912127910.3390/antiox912127933333846
     [Google Scholar]
  10. HanifF. MuzaffarK. PerveenK. MalhiS.M. SimjeeShU. Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment.APJCP20171813928239999
     [Google Scholar]
  11. StrobelH. BaischT. FitzelR. Temozolomide and other alkylating agents in glioblastoma therapy.Biomedicines2019736910.3390/biomedicines703006931505812
     [Google Scholar]
  12. BehranvandN. NasriF. EmamehZ.R. Chemotherapy: A double-edged sword in cancer treatment.Cancer Immunol. Immunother.202271350752610.1007/s00262‑021‑03013‑334355266
     [Google Scholar]
  13. GoldarS. KhanianiM.S. DerakhshanS.M. BaradaranB. Molecular mechanisms of apoptosis and roles in cancer development and treatment.Asian Pac. J. Cancer Prev.20151662129214410.7314/APJCP.2015.16.6.212925824729
     [Google Scholar]
  14. BukowskiK. KciukM. KontekR. Mechanisms of multidrug resistance in cancer chemotherapy.Int. J. Mol. Sci.2020219323310.3390/ijms2109323332370233
     [Google Scholar]
  15. JanR. ChaudhryG.S. Understanding apoptosis and apoptotic pathways targeted cancer therapeutics.Adv. Pharm. Bull.20199220521810.15171/apb.2019.02431380246
     [Google Scholar]
  16. HazafaA. RehmanK.U. JahanN. JabeenZ. The role of polyphenol (flavonoids) compounds in the treatment of cancer cells.Nutr. Cancer202072338639710.1080/01635581.2019.163700631287738
     [Google Scholar]
  17. HosseiniA. GhorbaniA. Cancer therapy with phytochemicals: Evidence from clinical studies.Avicenna J. Phytomed.201552849725949949
     [Google Scholar]
  18. SakK. Chemotherapy and dietary phytochemical agents.Chemother. Res. Pract.2012201228257010.1155/2012/282570
     [Google Scholar]
  19. OlivaM.A. StaffieriS. CastaldoS. GiangasperoF. EspositoV. ArcellaA. Characterization of primary glioma cell lines derived from the patients according to 2016 CNS tumour WHO classification and comparison with their parental tumours.J. Neurooncol.2021151212313310.1007/s11060‑020‑03673‑833398536
     [Google Scholar]
  20. Gomez-LechonM. DonatoM. LahozA. CastellJ. Cell lines: A tool for in vitro drug metabolism studies.Curr. Drug Metab.20089111110.2174/13892000878333108618220566
     [Google Scholar]
  21. ŠtamparM. BreznikB. FilipičM. ŽeguraB. Characterization of in vitro 3D cell model developed from human hepatocellular carcinoma (HepG2) Cell Line.Cells2020912255710.3390/cells912255733260628
     [Google Scholar]
  22. RassouliF.B. MatinM.M. IranshahiM. BahramiA.R. Investigating the cytotoxic and apoptosis inducing effects of monoterpenoid stylosin in vitro.Fitoterapia201182574274910.1016/j.fitote.2011.03.00521459136
     [Google Scholar]
  23. GoftariS.N. SadeghianH. BahramiA.R. MalekiF. MatinM.M. Stylosin and some of its synthetic derivatives induce apoptosis in prostate cancer cells as 15-lipoxygenase enzyme inhibitors.Naunyn Schmiedebergs Arch. Pharmacol.2019392121491150210.1007/s00210‑019‑01689‑031297564
     [Google Scholar]
  24. ValiahdiS.M. IranshahiM. SahebkarA. Cytotoxic activities of phytochemicals from Ferula species.Daru20132113910.1186/2008‑2231‑21‑3923701832
     [Google Scholar]
  25. Jalili-NikM. SabriH. ZamiriE. Cytotoxic effects of ferula Latisecta on human glioma U87 cells.Drug Res.2019691266567010.1055/a‑0986‑654331499542
     [Google Scholar]
  26. JavidH. AfshariA.R. MousaviS.H. Ferula gummosa gum exerts cytotoxic effects against human malignant glioblastoma multiforme in vitro.Res. Pharm. Sci.202217558559310.4103/1735‑5362.35521536386486
     [Google Scholar]
  27. HosseiniA. AlaviM.S. ShahrakiA.R. Psidium guajava induces cytotoxicity in human malignant glioblastoma cell line: Role of reactive oxygen species.Toxicol. In Vitro20238910556710.1016/j.tiv.2023.10556736758825
     [Google Scholar]
  28. TümenD. HeumannP. GülowK. Pathogenesis and current treatment strategies of hepatocellular carcinoma.Biomedicines20221012320210.3390/biomedicines1012320236551958
     [Google Scholar]
  29. MuzykaL. GoffN.K. ChoudharyN. KoltzM.T. Systematic review of molecular targeted therapies for adult-type diffuse glioma: An analysis of clinical and laboratory studies.Int. J. Mol. Sci.202324131045610.3390/ijms24131045637445633
     [Google Scholar]
  30. IsmailN.I. IbharmS.F. Chemotherapy–Types, Side Effects and Resistance.J Tomograp Syst Sensor Appl202032
     [Google Scholar]
  31. SarwarM.S. ZhangH.J. TsangS.W. Perspectives of plant natural products in inhibition of cancer invasion and metastasis by regulating multiple signaling pathways.Curr. Med. Chem.201925385057508710.2174/092986732466617091812341328925869
     [Google Scholar]
  32. MachanaS. WeerapreeyakulN. BarusruxS. Anticancer effect of the extracts from Polyalthia evecta against human hepatoma cell line (HepG2).Asian Pac. J. Trop. Biomed.20122536837410.1016/S2221‑1691(12)60058‑623569932
     [Google Scholar]
  33. MachadoT.Q. da FonsecaA.C. DuarteA. RobbsB.K. de SousaD.P. A narrative review of the antitumor activity of monoterpenes from essential oils: An update.BioMed Res. Int.202220226317201
     [Google Scholar]
  34. MahmoudvandH. Ghasemian YadegariJ. KhalafA.K. HashemiM.J. DastyarhaghighiS. SalimikiaI. Chemical composition, antileishmanial, and cytotoxic effects Ferula macrecolea essential oil against Leishmania tropica.Parasite Epidemiol. Control202219e0027010.1016/j.parepi.2022.e0027036118048
     [Google Scholar]
  35. IranshahiM. BarthomeufC. Bayet-RobertM. Drimane-type sesquiterpene coumarins from Ferula gummosa fruits enhance doxorubicin uptake in doxorubicin-resistant human breast cancer cell line.J. Tradit. Complement. Med.20144211812510.4103/2225‑4110.12618124860735
     [Google Scholar]
  36. ForouzmandS.H. MousaviS.H. VazifedanV. Synergistic effects of Ferula gummosa and radiotherapy on induction of cytotoxicity in HeLa cell line.Avicenna J. Phytomed.20188543947730345231
     [Google Scholar]
  37. IranshahiM. RezaeeR. NajafiN.M. HaghbinA. KasaianJ. Cytotoxic activity of the genus Ferula (Apiaceae) and its bioactive constituents.Avicenna J. Phytomed.20188429631230377589
     [Google Scholar]
  38. TalebpourA. AlipourR. SajjadiS.M. OsmaniF. SarabG.A. In vitro cytotoxicity of ferula asafoetida gum extract on human chronic myelogenous leukemia K562 cells.Pharm. Chem. J.202256224525310.1007/s11094‑022‑02627‑w
     [Google Scholar]
  39. MoradzadehM. SadeghniaH.R. MousaviS.H. MahmoodiM. HosseiniA. Ferula gummosa gum induces apoptosis via ROS mechanism in human leukemic cells.Cell. Mol. Biol.20176311172210.14715/cmb/2017.63.11.429208170
     [Google Scholar]
  40. TazikZ. RahnamaK. WhiteJ.F. SoltanlooH. HasanpourM. IranshahiM. LC-MS based identification of stylosin and tschimgine from fungal endophytes associated with Ferula ovina.Iran. J. Basic Med. Sci.202023121565157033489030
     [Google Scholar]
  41. SadeghiS. TabriziH.M. FarhadiA. Folic acid-chitosan coated stylosin nanostructured lipid carriers: Fabrication, in vitro–in vivo assessment in breast malignant cells.J. Biomater. Sci. Polym. Ed.202334679180910.1080/09205063.2022.214586836345914
     [Google Scholar]
  42. YaoK. XingH.C. WuB. Effect of TIEG1 on apoptosis and expression of Bcl-2/Bax and Pten in leukemic cell lines.Genet. Mol. Res.20151411968197410.4238/2015.March.20.625867342
     [Google Scholar]
  43. CarpenterR. BradyM.F. BAX gene.In:StatPearls.Treasure Island, FLStatPearls Publishing2020
     [Google Scholar]
  44. JangJ.H. SurhY.J. Potentiation of cellular antioxidant capacity by Bcl-2: Implications for its antiapoptotic function.Biochem. Pharmacol.20036681371137910.1016/S0006‑2952(03)00487‑814555211
     [Google Scholar]
  45. ReedJC MiyashitaT TakayamaS BCL-2 family proteins: Regulators of cell death involved in the pathogenesis of cancer and resistance to therapy.J Cell Biochem 1996601233210.1002/(SICI)1097‑4644(19960101)60:123::AID‑JCB53.0.CO;2‑58825412
     [Google Scholar]
  46. KellyP.N. StrasserA. The role of Bcl-2 and its pro-survival relatives in tumourigenesis and cancer therapy.Cell Death Differ.20111891414142410.1038/cdd.2011.1721415859
     [Google Scholar]
  47. HemannM.T. LoweS.W. The p53–Bcl-2 connection.Cell Death Differ.20061381256125910.1038/sj.cdd.440196216710363
     [Google Scholar]
  48. ProchazkovaJ. LichnovskyV. KylarovaD. ErdosovaB. VrankaP. Involvement of p53 and Bcl-2 family proteins in regulating programmed cell death and proliferation in human embryogenesis.Gen. Physiol. Biophys.200423220922915696860
     [Google Scholar]
  49. MiyashitaT. KrajewskiS. KrajewskaM. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo.Oncogene199496179918058183579
     [Google Scholar]
  50. ElmoreS. Apoptosis: A review of programmed cell death.Toxicol. Pathol.200735449551610.1080/0192623070132033717562483
     [Google Scholar]
  51. SilvaB.I.M. NascimentoE.A. SilvaC.J. SilvaT.G. AguiarJ.S. Anticancer activity of monoterpenes: A systematic review.Mol. Biol. Rep.20214875775578510.1007/s11033‑021‑06578‑534304392
     [Google Scholar]
  52. JayakumarT. LiuC.H. WuG.Y. Hinokitiol inhibits migration of A549 lung cancer cells via suppression of MMPs and induction of antioxidant enzymes and apoptosis.Int. J. Mol. Sci.201819493910.3390/ijms1904093929565268
     [Google Scholar]
/content/journals/ctm/10.2174/0122150838313458240524054119
Loading
Stylosin Exerts Cytotoxic and Apoptogenic Effects in Human Malignant Glioblastoma Line and Hepatocellular Carcinoma Cells: The Role of Reactive Oxygen Species
Current Traditional Medicine 12, E270624231396 (2026); https://doi.org/10.2174/0122150838313458240524054119
/content/journals/ctm/10.2174/0122150838313458240524054119
/content/journals/ctm/10.2174/0122150838313458240524054119
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): apoptosis; cancer; cytotoxicity; HepG2; Stylosin; U87

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