Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Proteomics
  4. Volume 21, Issue 5
  5. Article
Volume 21, Issue 5
  • ISSN: 1570-1646
  • E-ISSN: 1875-6247

Abstract

Background

Saffron (), also known as Red Gold has shown anticancer activity, but the molecular mechanisms underlying its potential therapeutic effects are not fully understood.

Objective

This study investigates the anticancer effects of safranal on cervical cancer, one of the most common cancer types in women worldwide, and elucidates the molecular mechanism underlying these effects through bioinformatics analysis RNA-sequencing.

Methods

The molecular mechanisms and key genes underlying the antiproliferative effect of safranal (400μM) on cervical cancer cells were determined with RNA sequencing bioinformatics analysis.

Results

The total number of expressed genes in HeLa and C- 4 I was determined as 1101 and 1190, respectively after 24 hours of incubation of safranal. KDA showed the key driver genes EIF2AK2, USP18, PARP14, GBP1, SAMD9L, SP110, DDX60, IFI44L and MX2 of the HeLa group, while in the C- 4 I group, key driver genes are DNAJC3, DNAJB9, DNAJB8, SRPX2, PRSS8, MRC2, IER2, RPS19BP1, CRELD2 and SDF2L1. KEGG and GO analysis revealed that safranal induced cell arrest in the G1 phase, cell death apoptosis, and necroptosis in cervical cancer cells. These antiproliferative effects were shown based on regulated signaling pathways: MAPK, TGF-beta, p-53, TNF and FoxO signaling pathways.

Conclusion

Based on the results obtained by RNA sequencing, it can be concluded that safranal has a potential antiproliferative effect and could be used in the clinic as an anticancer agent.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cp/10.2174/0115701646318807240830052736
2025-01-01
2025-06-26

  • From This Site

    /content/journals/cp/10.2174/0115701646318807240830052736
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. BaykaraO. Kanser Tedavisinde Güncel Yaklaşımlar.Balıkesir Sağlık Bilimleri Dergisi201653154165
     [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. HosseinzadehE. BanaeeN. NedaieH.A. Cancer and treatment modalities.Curr. Cancer Ther. Rev.2017131172710.2174/1573394713666170531081818
     [Google Scholar]
  4. SiegelR.L. MillerK.D. JemalA. Cancer statistics, 2020.CA Cancer J. Clin.202070173010.3322/caac.2159031912902
     [Google Scholar]
  5. HosseinzadehH. ShamsaieF. MehriS. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal.Pharmacogn. Mag.2009520419
     [Google Scholar]
  6. SaririR. SabbaghzadehR. PoumohamadF. In-vitro antioxidant and anti-tyrosinase activity of methanol extracts from Crocus sativus flowers.Pharmacologyonline20113111
     [Google Scholar]
  7. MadanK. NandaS. In-vitro evaluation of antioxidant, anti-elastase, anti-collagenase, anti-hyaluronidase activities of safranal and determination of its sun protection factor in skin photoaging.Bioorg. Chem.20187715916710.1016/j.bioorg.2017.12.03029353733
     [Google Scholar]
  8. PanP-K. QiaoL-Y. WenX-N. Safranal prevents rotenone-induced oxidative stress and apoptosis in an in vitro model of Parkinson’s disease through regulating Keap1/Nrf2 signaling pathway.Cell. Mol. Biol.20166214111710.14715/cmb/2016.62.14.228145852
     [Google Scholar]
  9. SamarghandianS. Azimi-NezhadM. FarkhondehT. Immunomodulatory and antioxidant effects of saffron aqueous extract ( Crocus sativus L.) on streptozotocin-induced diabetes in rats.Indian Heart J.201769215115910.1016/j.ihj.2016.09.00828460761
     [Google Scholar]
  10. BaluchnejadmojaradT. Mohamadi-ZarchS.M. RoghaniM. Safranal, an active ingredient of saffron, attenuates cognitive deficits in amyloid β-induced rat model of Alzheimer’s disease: Underlying mechanisms.Metab. Brain Dis.20193461747175910.1007/s11011‑019‑00481‑631422512
     [Google Scholar]
  11. ZhangY. ZhaoY. GuoJ. CuiH. LiuS. Anticancer activity of safranal against colon carcinoma is due to induction of apoptosis and G2/M cell cycle arrest mediated by suppression of mTOR/PI3K/Akt pathway.J. BUON201823357457830003721
     [Google Scholar]
  12. KoulA. AbrahamS.K. Efficacy of crocin and safranal as protective agents against genotoxic stress induced by gamma radiation, urethane and procarbazine in mice.Hum. Exp. Toxicol.2018371132010.1177/096032711668971528111973
     [Google Scholar]
  13. LozonL. SalehE. MenonV. RamadanW.S. AminA. El-AwadyR. Effect of safranal on the response of cancer cells to topoisomerase I inhibitors: Does sequence matter?Front. Pharmacol.20221393847110.3389/fphar.2022.93847136120345
     [Google Scholar]
  14. AshrafianS. ZarrinehM. JensenP. NawrockiA. RezadoostH. AnsariA.M. FarahmandL. GhassempourA. LarsenM.R. Quantitative phosphoproteomics and acetylomics of safranal anticancer effects in triple-negative breast cancer cells.J. Proteome Res.202221112566258510.1021/acs.jproteome.2c0016836173113
     [Google Scholar]
  15. ZarrinehM. AshrafianS. JensenP. NawrockiA. AnsariA.M. RezadoostH. GhassempourA. LarsenM.R. Comprehensive proteomics and sialiomics of the anti-proliferative activity of safranal on triple negative MDA-MB-231 breast cancer cell lines.J. Proteomics202225910453910.1016/j.jprot.2022.10453935240313
     [Google Scholar]
  16. AliS.A. Karabulut-BulanO. ÖzcanF.G. Evaluation of the Antiproliferative Effect of Safranal in C-4 I Cervical Cancer Cell Line.East Black Sea J. Health Sci.20242117128
     [Google Scholar]
  17. CheriyamundathS. ChoudharyS. LopusM. Safranal inhibits HeLa cell viability by perturbing the reassembly potential of microtubules.Phytother. Res.201832117017310.1002/ptr.593829024138
     [Google Scholar]
  18. SamarghandianS. BorjiA. DelkhoshM.B. SaminiF. Safranal treatment improves hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced diabetic rats.J. Pharm. Pharm. Sci.201316235236210.18433/J3ZS3Q23958204
     [Google Scholar]
  19. AbdallaY. AbdallaA. HamzaA.A. AminA. Safranal prevents liver cancer through inhibiting oxidative stress and alleviating inflammation.Front. Pharmacol.20221277750010.3389/fphar.2021.77750035177980
     [Google Scholar]
  20. YangX. LuD. SunY. WeiT. ManD. ChenA. LuoT. ZhaoF. LiuX. ChengB. WangX. ZhaoP. WangD. LiX. Network pharmacology and experimental verification reveal the mechanism of safranal against glioblastoma (GBM).Front. Oncol.202313125516410.3389/fonc.2023.125516437736545
     [Google Scholar]
  21. ForouzanfarF. AsadpourE. HosseinzadehH. BoroushakiM.T. AdabA. DastpeimanS.H. SadeghniaH.R. Safranal protects against ischemia-induced PC12 cell injury through inhibiting oxidative stress and apoptosis.Naunyn Schmiedebergs Arch. Pharmacol.2021394470771610.1007/s00210‑020‑01999‑833128592
     [Google Scholar]
  22. Al-HroutA.A. ChaiboonchoeA. KhraiweshB. Safranal induces DNA double-strand breakage and ER-stress-mediated cell death in hepatocellular carcinom cells.Sci. Rep.2018811695110.1038/s41598‑018‑34855‑030446676
     [Google Scholar]
  23. RafieipourF. HadipourE. EmamiS.A. AsiliJ. Tayarani-NajaranZ. Safranal protects against beta-amyloid peptide-induced cell toxicity in PC12 cells via MAPK and PI3 K pathways.Metab. Brain Dis.201934116517210.1007/s11011‑018‑0329‑930402809
     [Google Scholar]
  24. JiangX. LiY. FengJ. Nik NabilW.N. WuR. LuY. LiuH. XiZ. XuH. Safrana l prevents prostate cancer recurrence by blocking theRe-activation of quiescent cancer cells via downregulation of S-phase kinase-associated protein 2.Front. Cell Dev. Biol.2020859862010.3389/fcell.2020.59862033392189
     [Google Scholar]
  25. IARCGlobocan Cancer TODAY.2022Available From: https://gco.iarc.fr/today/en/dataviz/pie?mode=population&cancers=39&group_populations=0&types=0&sexes=2
  26. ParkinD.M. BrayF. Chapter 2: The burden of HPV-related cancers.Vaccine200624Suppl. 3S11S2510.1016/j.vaccine.2006.05.11116949997
     [Google Scholar]
  27. ZhangS.P. HuangJ.N. JinN. WangX. L. JinC.C. Safranal inhibits the migration and invasion of human oral squamous cell carcinoma cells by overcoming epithelial-mesenchymal transition.Biomed. Res.2017282217221
     [Google Scholar]
  28. ZhangS. XuH. ZhangL. QiaoY. Cervical cancer: Epidemiology, risk factors and screening.Chin. J. Cancer Res.202032672072810.21147/j.issn.1000‑9604.2020.06.0533446995
     [Google Scholar]
  29. del Toro-ArreolaS. García-ChagollánM. Jave-SuárezL.F. [Escape mechanisms to the innate immune response in HPV-associated cervical cancer].Rev. Med. Inst. Mex. Seguro Soc.201553Suppl. 2S194S19926462516
     [Google Scholar]
  30. CohenP.A. JhingranA. OakninA. DennyL. Cervical cancer.Lancet20193931016716918210.1016/S0140‑6736(18)32470‑X30638582
     [Google Scholar]
  31. BalasubramaniamS.D. BalakrishnanV. OonC.E. KaurG. Key molecular events in cervical cancer development.Medicina (Kaunas)201955738410.3390/medicina5507038431319555
     [Google Scholar]
  32. RíosJ.L. RecioM.C. GinerR.M. MáñezS. An update review of saffron and its active constituents.Phytother. Res.199610318919310.1002/(SICI)1099‑1573(199605)10:3<189::AID‑PTR754>3.0.CO;2‑C
     [Google Scholar]
  33. MollazadehH. EmamiS.A. HosseinzadehH. Razi’s Al-Hawi and saffron (Crocus sativus): A review.Iran. J. Basic Med. Sci.201518121153116626877844
     [Google Scholar]
  34. EscribanoJ. AlonsoG.L. Coca-PradosM. FernándezJ.A. Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro.Cancer Lett.19961001-2233010.1016/0304‑3835(95)04067‑68620447
     [Google Scholar]
  35. RezaeeR. HosseinzadehH. Safranal: From an aromatic natural product to a rewarding pharmacological agent.Iran. J. Basic Med. Sci.2013161122623638289
     [Google Scholar]
  36. RameshradM. RazaviB.M. HosseinzadehH. Saffron and its derivatives, crocin, crocetin and safranal: A patent review.Expert Opin. Ther. Pat.201828214716510.1080/13543776.2017.135590928705037
     [Google Scholar]
  37. DograA. KotwalP. GourA. BhattS. SinghG. MukherjeeD. NandiU. Description of druglike properties of safranal and its chemistry behind low oral exposure.ACS Omega20205179885989110.1021/acsomega.0c0016032391475
     [Google Scholar]
  38. HosseinzadehH. Nassiri-AslM. Avicenna’s (Ibn Sina) the canon of medicine and saffron (Crocus sativus): A review.Phytother. Res.201327447548310.1002/ptr.478422815242
     [Google Scholar]
  39. Dagdeviren OzsoylemezO. OzcanG. The antiproliferative activity of colchicum umbrosum plant extract and paclitaxel on C-4 I and vero cells.European J. Biol.2019772818810.26650/EurJBiol.2018.0016
     [Google Scholar]
  40. KukurbaK.R. MontgomeryS.B. RNA sequencing and analysis.Cold Spring Harb. Protoc.2015201511pdb.top08497010.1101/pdb.top08497025870306
     [Google Scholar]
  41. CockP.J.A. FieldsC.J. GotoN. HeuerM.L. RiceP.M. The Sanger FASTQ file format for sequences with quality scores, and the Solexa/Illumina FASTQ variants.Nucleic Acids Res.20103861767177110.1093/nar/gkp113720015970
     [Google Scholar]
  42. KimD. LangmeadB. SalzbergS.L. HISAT: A fast spliced aligner with low memory requirements.Nat. Methods201512435736010.1038/nmeth.331725751142
     [Google Scholar]
  43. AliS.A. ÖzcanF.G. BulanÖ.K. Bioinformatic analysis of the anti-cancer effects of Safranal via the p53 signaling pathway in cervical cancer cell lines.Proceedings202410314110.3390/proceedings2024103041
     [Google Scholar]
  44. ChenJ. ZhaoK.N. HPV-p53-miR-34a axis in HPV-associated cancers.Ann. Transl. Med.201532133126734641
     [Google Scholar]
  45. DolmaL. MullerP.A.J. GOF mutant p53 in cancers: A therapeutic challenge.Cancers (Basel)20221420509110.3390/cancers1420509136291874
     [Google Scholar]
  46. Todorović-RakovićN. MilovanovićJ. Nikolić-VukosavljevićD. TGF-β and its coreceptors in cancerogenesis: An overview.Biomarkers Med.20115685586310.2217/bmm.11.5922103622
     [Google Scholar]
  47. GuoY.J. PanW.W. LiuS.B. ShenZ.F. XuY. HuL.L. ERK/MAPK signalling pathway and tumorigenesis.Exp. Ther. Med.20201931997200732104259
     [Google Scholar]
  48. BerettaG.L. CornoC. ZaffaroniN. PeregoP. Role of FoxO proteins in cellular response to antitumor agents.Cancers (Basel)20191119010.3390/cancers1101009030646603
     [Google Scholar]
  49. GrabarekB. BednarczykM. MazurekU. The characterization of tumor necrosis factor alpha (TNF-α), its role in cancerogenesis and cardiovascular system diseases and possibilities of using this cytokine as a molecular marker.Acta Universitatis Lodziensis Folia Biologica et Oecol.201913118
     [Google Scholar]
  50. ChangL. KarinM. Mammalian MAP kinase signalling cascades.Nature20014106824374010.1038/3506500011242034
     [Google Scholar]
  51. GollobJ.A. WilhelmS. CarterC. KelleyS.L. Role of Raf kinase in cancer: Therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway.Semin. Oncol.2006334392406
     [Google Scholar]
  52. YoshidaS. KajitaniN. SatsukaA. NakamuraH. SakaiH. Ras modifies proliferation and invasiveness of cells expressing human papillomavirus oncoproteins.J. Virol.200882178820882710.1128/JVI.02363‑0718579583
     [Google Scholar]
  53. DaviesS.P. ReddyH. CaivanoM. CohenP. Specificity and mechanism of action of some commonly used protein kinase inhibitors.Biochem. J.200035119510510.1042/bj351009510998351
     [Google Scholar]
  54. KersemaekersA.M.F. FleurenG.J. KenterG.G. Van den BroekL.J. UljeeS.M. HermansJ. Van de VijverM.J. Oncogene alterations in carcinomas of the uterine cervix: Overexpression of the epidermal growth factor receptor is associated with poor prognosis.Clin. Cancer Res.19995357758610100709
     [Google Scholar]
  55. LiQ. TangY. ChengX. JiJ. ZhangJ. ZhouX. EGFR protein expression and gene amplification in squamous intraepithelial lesions and squamous cell carcinomas of the cervix.Int. J. Clin. Exp. Pathol.20147273374124551297
     [Google Scholar]
  56. YueJ. LópezJ.M. Understanding MAPK signaling pathways in apoptosis.Int. J. Mol. Sci.2020217234610.3390/ijms2107234632231094
     [Google Scholar]
/content/journals/cp/10.2174/0115701646318807240830052736
Loading
Molecular Mechanisms of Antiproliferative Effects of Safranal on Cervical Cancer: Evidence from Bioinformatics Analysis
Curr. Proteomics 21, 392 (2024); https://doi.org/10.2174/0115701646318807240830052736
/content/journals/cp/10.2174/0115701646318807240830052736
/content/journals/cp/10.2174/0115701646318807240830052736
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): antiproliferative; apoptosis; cell cycle; cervical cancer; genes; necroptosis; RNA seq; Safranal

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