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2000
Volume 25, Issue 17
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Background

In the past few years, the antiproliferative activities of chrysin (5,7-dihydroxyflavone) have garnered significant attention in anticancer drug discovery due to its promising ability to suppress cancer cell proliferation. However, studies on its effects on cervical cancer are limited and have primarily focused on HeLa cells.

Objective

In order to better understand its therapeutic potential for cervical cancer, we assessed the antiproliferative and anti-migratory effects of chrysin in a wide range of human-derived cell lines comprising C33A (human papillomavirus/HPV-negative), HeLa (HPV 18-positive), SiHa (HPV 16-positive), and CaSKi (HPV 16 and 18-positive), in comparison to a human epithelial cell line derived from spontaneously immortalized cell, HaCaT.

Methods

Cell viability was determined using the MTT assay, while the clonogenic assay evaluated long-term cytotoxicity. Morphological alterations were observed light microscopy, and cell death was assessed using Annexin V FITC/propidium iodide (PI) staining. Total reactive oxygen species (ROS) levels were measured by fluorescence microscopy, the mitochondrial transmembrane potential was assessed using TMRE, and lipid peroxidation was analyzed using DPPP. Additionally, wound healing migration and cell invasion assays were conducted.

Results

Chrysin selectively inhibited cell proliferation and induced apoptosis in every cervical cancer cell line assessed while exerting minimal effects on HaCaT cells. Additionally, it triggered mitochondrial redox imbalance and significantly suppressed both migration and invasion of cervical cancer cells.

Conclusion

Based on these results, chrysin appears to be a promising candidate as an anticancer agent for both HPV-associated and HPV-independent cervical cancers, emphasizing the necessity for further exploration in subsequent studies.

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2025-03-21
2025-09-08

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References

  1. SinghD. VignatJ. LorenzoniV. EslahiM. GinsburgO. Lauby-SecretanB. ArbynM. BasuP. BrayF. VaccarellaS. Global estimates of incidence and mortality of cervical cancer in 2020: A baseline analysis of the WHO Global Cervical cancer elimination initiative.Lancet Glob. Health2023112e197e20610.1016/S2214‑109X(22)00501‑0 36528031
     [Google Scholar]
  2. BriantiP. De FlammineisE. MercuriS.R. Review of HPV-related diseases and cancers.New Microbiol.20174028085 28368072
     [Google Scholar]
  3. LorussoD. PetrelliF. CoinuA. RaspagliesiF. BarniS. RaspagliesiF. A systematic review comparing cisplatin and carboplatin plus paclitaxel-based chemotherapy for recurrent or metastatic cervical cancer.Gynecol. Oncol.2014133111712310.1016/j.ygyno.2014.01.042 24486604
     [Google Scholar]
  4. BarraF. LorussoD. MaggioreU.L.R. DittoA. BoganiG. RaspagliesiF. FerreroS. Investigational drugs for the treatment of cervical cancer.Expert Opin. Investig. Drugs201726438940210.1080/13543784.2017.1302427 28274154
     [Google Scholar]
  5. VistadI. FossåS.D. DahlA.A. A critical review of patient-rated quality of life studies of long-term survivors of cervical cancer.Gynecol. Oncol.2006102356357210.1016/j.ygyno.2006.03.050 16716379
     [Google Scholar]
  6. MishraN. SinghN. SachdevaM. GhatageP. Sexual dysfunction in cervical cancer survivors: A scoping review.Women's Health Reports20212159460710.1089/whr.2021.0035 35141708
     [Google Scholar]
  7. FuZ.Z. LiK. PengY. ZhengY. CaoL.Y. ZhangY.J. SunY.M. Efficacy and toxicity of different concurrent chemoradiotherapy regimens in the treatment of advanced cervical cancer.Medicine (Baltimore)2017962e585310.1097/MD.0000000000005853 28079819
     [Google Scholar]
  8. KinghornA.D. De BlancoE.J.C. LucasD.M. RakotondraibeH.L. OrjalaJ. SoejartoD.D. OberliesN.H. PearceC.J. WaniM.C. StockwellB.R. BurdetteJ. SwansonS.M. FuchsJ.R. PhelpsM.A. XuL. ZhangX. ShenY.Y. Discovery of anticancer agents of diverse natural origin.Anticancer Res.201636115623563810.21873/anticanres.11146 27793884
     [Google Scholar]
  9. de Freitas MeirellesL.E. de Assis CarvalhoA.R.B. Ferreira DamkeG.M.Z. SouzaR.P. DamkeE. de Souza Bonfim-MendonçaP. de Oliveira DembogurskiD.S. da SilvaD.B. ConsolaroM.E.L. da SilvaV.R.S. Antitumoral potential of Artepillin C, a compound derived from Brazilian propolis, against breast cancer cell lines.Anticancer. Agents Med. Chem.202424211712410.2174/0118715206270534231103074433 37957873
     [Google Scholar]
  10. SouzaR.P. Bonfim-MendonçaP.S. GimenesF. RattiB.A. KaplumV. BruschiM.L. NakamuraC.V. SilvaS.O. Maria-EnglerS.S. ConsolaroM.E.L. Oxidative stress triggered by apigenin induces apoptosis in a comprehensive panel of human cervical cancer-derived cell lines.Oxid. Med. Cell. Longev.201720171151274510.1155/2017/1512745 28191273
     [Google Scholar]
  11. KasalaE.R. BodduluruL.N. MadanaR.M. v, A.K.; Gogoi, R.; Barua, C.C. Chemopreventive and therapeutic potential of chrysin in cancer: Mechanistic perspectives.Toxicol. Lett.2015233221422510.1016/j.toxlet.2015.01.008 25596314
     [Google Scholar]
  12. FarkhondehT. SamarghandianS. BafandehF. The cardiovascular protective effects of chrysin: A narrative review on experimental research.Cardiovasc. Hematol. Agents Med. Chem.2019171172710.2174/1871525717666190114145137 30648526
     [Google Scholar]
  13. RyuS. LimW. BazerF.W. SongG. Chrysin induces death of prostate cancer cells by inducing ROS and ER stress.J. Cell. Physiol.2017232123786379710.1002/jcp.25861 28213961
     [Google Scholar]
  14. WooK.J. JeongY.J. ParkJ.W. KwonT.K. Chrysin-induced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells.Biochem. Biophys. Res. Commun.200432541215122210.1016/j.bbrc.2004.09.225 15555556
     [Google Scholar]
  15. LimW. RyuS. BazerF.W. KimS.M. SongG. Chrysin attenuates progression of ovarian cancer cells by regulating signaling cascades and mitochondrial dysfunction.J. Cell. Physiol.201823343129314010.1002/jcp.26150 28816359
     [Google Scholar]
  16. ZhangQ. ZhaoX.H. WangZ.J. Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line (KYSE-510) by induction of G2/M arrest and apoptosis.Toxicol. In vitro200923579780710.1016/j.tiv.2009.04.007 19397994
     [Google Scholar]
  17. KasalaE.R. BodduluruL.N. BaruaC.C. GogoiR. Chrysin and its emerging role in cancer drug resistance.Chem. Biol. Interact.20152367810.1016/j.cbi.2015.04.017 25912556
     [Google Scholar]
  18. LaishramS. MoirangthemD.S. BorahJ.C. PalB.C. SumanP. GuptaS.K. KalitaM.C. TalukdarN.C. Chrysin rich Scutellaria discolor Colebr. induces cervical cancer cell death via the induction of cell cycle arrest and caspase-dependent apoptosis.Life Sci.201514310511310.1016/j.lfs.2015.10.035 26541229
     [Google Scholar]
  19. TangQ. JiF. GuoJ. WangJ. LiY. BaoY. Directional modification of chrysin for exerting apoptosis and enhancing significantly anti-cancer effects of 10-hydroxy camptothecin.Biomed. Pharmacother.20168269370310.1016/j.biopha.2016.06.008 27470413
     [Google Scholar]
  20. ZhangT. ChenX. QuL. WuJ. CuiR. ZhaoY. Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis in Hela cells.Bioorg. Med. Chem.200412236097610510.1016/j.bmc.2004.09.013 15519155
     [Google Scholar]
  21. RainaR. AfrozeN. SundaramM.K. HaqueS. BajboujK. HamadM. HussainA. Chrysin inhibits propagation of HeLa cells by attenuating cell survival and inducing apoptotic pathways.Eur. Rev. Med. Pharmacol. Sci.202125522062220 33755959
     [Google Scholar]
  22. LeonI.E. Di VirgilioA.L. PorroV. MugliaC.I. NasoL.G. WilliamsP.A.M. Bollati-FogolinM. EtcheverryS.B. Antitumor properties of a vanadyl(iv) complex with the flavonoid chrysin [VO(chrysin)2EtOH]2 in a human osteosarcoma model: The role of oxidative stress and apoptosis.Dalton Trans.20134233118681188010.1039/c3dt50524c 23760674
     [Google Scholar]
  23. Di MeoS. ReedT.T. VendittiP. VictorV.M. Role of ROS and RNS sources in physiological and pathological conditions.Oxid. Med. Cell. Longev.201620161245049
     [Google Scholar]
  24. TwentymanP.R. LuscombeM. A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity.Br. J. Cancer198756279285
     [Google Scholar]
  25. FrankenN.A.P. RodermondH.M. StapJ. HavemanJ. van BreeC. Clonogenic assay of cells in vitro.Nat. Protoc.2006152315231910.1038/nprot.2006.339 17406473
     [Google Scholar]
  26. IqbalB. GhildiyalA. SahabjadaS. SinghS. ArshadM. MahdiA.A. TiwariS. Antiproliferative and apoptotic effect of curcumin and TRAIL (TNF related apoptosis inducing ligand) in chronic myeloid leukaemic cells.J. Clin. Diagn. Res.2016104XC01XC0510.7860/JCDR/2016/18507.7579 27190933
     [Google Scholar]
  27. ShuklaA.K. PatraS. DubeyV.K. Iridoid glucosides from Nyctanthes arbortristis result in increased reactive oxygen species and cellular redox homeostasis imbalance in Leishmania parasite.Eur. J. Med. Chem.201254495810.1016/j.ejmech.2012.04.034 22608855
     [Google Scholar]
  28. XuJ. HaoZ. GouX. TianW. JinY. CuiS. GuoJ. SunY. WangY. XuZ. Imaging of reactive oxygen species burst from mitochondria using laser scanning confocal microscopy.Microsc. Res. Tech.201376661261710.1002/jemt.22207 23580478
     [Google Scholar]
  29. OkimotoY. WatanabeA. NikiE. YamashitaT. NoguchiN. A novel fluorescent probe diphenyl‐1‐pyrenylphosphine to follow lipid peroxidation in cell membranes.FEBS Lett.20004742-313714010.1016/S0014‑5793(00)01587‑8 10838073
     [Google Scholar]
  30. LiangC.C. ParkA.Y. GuanJ.L. In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro.Nat. Protoc.20072232933310.1038/nprot.2007.30 17406593
     [Google Scholar]
  31. TominK. GoldfarbR.H. AlbertssonP. In vitro assessment of human natural killer cell migration and invasion.Methods Mol. Biol.20161441657410.1007/978‑1‑4939‑3684‑7_6 27177657
     [Google Scholar]
  32. PatelR.V. MistryB. SyedR. RathiA.K. LeeY.J. SungJ.S. ShinfH.S. KeumY.S. Chrysin-piperazine conjugates as antioxidant and anticancer agents.Eur. J. Pharm. Sci.20168816617710.1016/j.ejps.2016.02.011 26924226
     [Google Scholar]
  33. MistryB.M. PatelR.V. KeumY.S. KimD.H. Chrysin–benzothiazole conjugates as antioxidant and anticancer agents.Bioorg. Med. Chem. Lett.201525235561556510.1016/j.bmcl.2015.10.052 26514745
     [Google Scholar]
  34. ZhangQ. MaS. LiuB. LiuJ. ZhuR. LiM. Chrysin induces cell apoptosis via activation of the p53/Bcl-2/caspase-9 pathway in hepatocellular carcinoma cells.Exp. Ther. Med.201612146947410.3892/etm.2016.3282 27347080
     [Google Scholar]
  35. SiesH. Strategies of antioxidant defense.Eur. J. Biochem.1993215221321910.1111/j.1432‑1033.1993.tb18025.x 7688300
     [Google Scholar]
  36. AcharyaA. DasI. ChandhokD. SahaT. Redox regulation in cancer: A double-edged sword with therapeutic potential.Oxid. Med. Cell. Longev.201031233410.4161/oxim.3.1.10095 20716925
     [Google Scholar]
  37. SalimiA. RoudkenarM.H. SeydiE. SadeghiL. MohseniA. PirahmadiN. PourahmadJ. Chrysin as an anti-cancer agent exerts selective toxicity by directly inhibiting mitochondrial complex II and V in CLL B-lymphocytes.Cancer Invest.201735317418610.1080/07357907.2016.1276187 28301251
     [Google Scholar]
  38. ParkW. ParkS. LimW. SongG. Chrysin disrupts intracellular homeostasis through mitochondria-mediated cell death in human choriocarcinoma cells.Biochem. Biophys. Res. Commun.201850343155316110.1016/j.bbrc.2018.08.109 30139515
     [Google Scholar]
  39. DongreA. WeinbergR.A. New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer.Nat. Rev. Mol. Cell Biol.2019202698410.1038/s41580‑018‑0080‑4 30459476
     [Google Scholar]
  40. PuisieuxA. BrabletzT. CaramelJ. Oncogenic roles of EMT-inducing transcription factors.Nat. Cell Biol.201416648849410.1038/ncb2976 24875735
     [Google Scholar]
  41. PrangsaengtongO. AthikomkulchaiS. XuJ. KoizumiK. InujimaA. ShibaharaN. ShimadaY. TadtongS. AwaleS. Chrysin inhibits lymphangiogenesis in vitro.Biol. Pharm. Bull.201639446647210.1248/bpb.b15‑00543 27040620
     [Google Scholar]
  42. YangB. HuangJ. XiangT. YinX. LuoX. HuangJ. LuoF. LiH. LiH. RenG. Chrysin inhibits metastatic potential of human triple‐negative breast cancer cells by modulating matrix metalloproteinase‐10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway.J. Appl. Toxicol.201434110511210.1002/jat.2941 24122885
     [Google Scholar]
  43. YufeiZ. YuqiW. BinyueH. LingchenT. XiC. HoffeltD. FuliangH. Chrysin inhibits melanoma tumor metastasis via interfering with the FOXM1/β-Catenin signaling.J. Agric. Food Chem.202068359358936710.1021/acs.jafc.0c03123 32797754
     [Google Scholar]
  44. RainaR. AlmutaryA.G. BagabirS.A. AfrozeN. FagooneeS. HaqueS. HussainA. Chrysin modulates aberrant epigenetic variations and hampers migratory behavior of human cervical (HeLa) cells.Front. Genet.20221276813010.3389/fgene.2021.768130 35096000
     [Google Scholar]
  45. DongW. ChenA. ChaoX. LiX. CuiY. XuC. CaoJ. NingY. Chrysin inhibits proinflammatory factor-induced EMT phenotype and cancer stem cell-like features in HeLa Cells by blocking the NF-κB/Twist axis.Cell. Physiol. Biochem.20195251236125010.33594/000000084 31001962
     [Google Scholar]
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Chrysin Exhibits Selective Antiproliferative and Antimigratory Activities in a Wide Range of Human-derived Cervical Cancer Cell Lines
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 1311 (2025); https://doi.org/10.2174/0118715206366318250312052617
/content/journals/acamc/10.2174/0118715206366318250312052617
/content/journals/acamc/10.2174/0118715206366318250312052617
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  • Article Type:     Research Article
Keyword(s): antimigratory; antiproliferative; Cervical cancer; chrysin; HaCaT cells; treatment

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