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Volume 21, Issue 6
  • ISSN: 1573-4072
  • E-ISSN: 1875-6646

Abstract

Introduction

Cucurbitacin-induced apoptosis and inhibition of cell growth can render several cancers ineffective. The microbial transformation of cucurbitacin-E-glucoside to cucurbitacin-E was carried out by (NRRL 2178). Moreover, anticancer activity against the MCF-7 cell line as well as anticancer activity against dimethylbenz (a) anthracene (DMBA)-induced breast cancer in mice using cucurbitacin-E was evaluated.

Methods

The cucurbitacin-E-glucoside was biotransformed by to cucurbitacin-E, and the isolated compound was tested against the MCF-7 cell line, and its IC was calculated. LD of cucurbitacin-E was estimated in mice, and its protective activity against DMBA-induced cancer in mice was studied. Breast cancer induction was done by a single-dose subcutaneous administration of DMBA (50 mg). Plasma ALT, AST, ALP, and LDH, as well as GSH, SOD, GPx, MDA, TNF-α, IL-6, and tumor suppressor P53 assays, were used to assess cucurbitacin-E's capacity to protect the liver and breast against DMBA-induced toxicity. Moreover, by assessing the gene expression of tumor suppressor genes (BRCA 1 and 2) and conducting histopathological analysis, the suppressive effect of cucurbitacin-E was examined.

Results

The IC value of cucurbitacin-E against MCF-7 cell lines equals 72.15 ± 0.64 µg/ml. LD of cucurbitacin-E given orally in adult mice is equal to 1200 mg/kg b.w. The levels of plasma ALT, AST, ALP, and LDH were decreased significantly in DMBA-treated mice when administered with cucurbitacin-E at 1/50 LD (24 mg/kg/b.w.) and 1/20 LD (60 mg/kg/b.w.). In breast tissue, the levels of GSH, SOD, GPx, and P53 were significantly increased, as were decreased levels of TNF-α, IL-6, P53, and MDA. Conversely, there was a downregulation in the mRNA expression levels of BRCA1 and BRCA2. The histopathological analysis revealed that cucurbitacin-E management improved the tissue architecture of breast tumors.

Conclusion

These findings demonstrate the ability of cucurbitacin-E to inhibit cancer cells in the rat breast by controlling oxidative stress and inflammatory biomarkers, as well as downregulating the mRNA expression levels of BRCA1 and BRCA2.

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References

  1. WHO, Breast cancer2023Available from: https://www.who.int/news-room/fact-sheets/detail/breast-cancer (accessed on 31-8-2024)
  2. YinS.Y. WeiW.C. JianF.Y. YangN.S. Therapeutic applications of herbal medicines for cancer patients.Evid. Based Complement. Alternat. Med.2013201311510.1155/2013/302426 23956768
     [Google Scholar]
  3. ShirodeA.B. BharaliD.J. NallanthighalS. CoonJ.K. MousaS.A. RelieneR. Nanoencapsulation of pomegranate bioactive compounds for breast cancer chemoprevention.Int. J. Nanomedicine201510475484 25624761
     [Google Scholar]
  4. El GizawyH.A.E.H. HusseinM.A. Abdel-SattarE. Biological activities, isolated compounds and HPLC profile of Verbascum nubicum.Pharm. Biol.201957148549710.1080/13880209.2019.1643378 31401911
     [Google Scholar]
  5. HusseinM.A. Prophylactic effect of resveratrol against ethinylestradiol-induced liver cholestasis.J. Med. Food201316324625410.1089/jmf.2012.0183 23305807
     [Google Scholar]
  6. HusseinM.A. IsmailN.E.M. MohamedA.H. BorikR.M. AliA.A. MosaadY.O. Plasma phospholipids: A promising simple biochemical parameter to evaluate COVID-19 infection severity.Bioinform. Biol. Insights20211510.1177/11779322211055891 34840499
     [Google Scholar]
  7. ShehataM.R. MohamedM.M.A. ShoukryM.M. HusseinM.A. HusseinF.M. HusseinF.M. Synthesis, characterization, equilibria and biological activity of dimethyltin(IV) complex with 1,4-piperazine.J. Coord. Chem.20156861101111410.1080/00958972.2015.1007962
     [Google Scholar]
  8. Mohammed AbdallaH.Jr Soad MohamedA.G. In vivo hepato-protective properties of purslane extracts on paracetamol-induced liver damage.Malays. J. Nutr.2010161161170 22691863
     [Google Scholar]
  9. MohamadE.A. MohamedZ.N. HusseinM.A. ElneklawiM.S. GANE can improve lung fibrosis by reducing inflammation via promoting p38MAPK/TGF-β1/NF-κB signaling pathway downregulation.ACS Omega2022733109312010.1021/acsomega.1c06591 35097306
     [Google Scholar]
  10. El GizawyH.A. Abo-SalemH.M. AliA.A. HusseinM.A. Phenolic profiling and therapeutic potential of certain isolated compounds from Parkia roxburghii against AChE activity as well as GABA A α5, GSK-3β, and p38α MAP-kinase genes.ACS Omega2021631204922051110.1021/acsomega.1c02340 34395996
     [Google Scholar]
  11. GobbaN.A.E.K. Hussein AliA. El SharawyD.E. HusseinM.A. The potential hazardous effect of exposure to iron dust in Egyptian smoking and nonsmoking welders.Arch. Environ. Occup. Health201873318920210.1080/19338244.2017.1314930 28375782
     [Google Scholar]
  12. TeohP.L. LiauM. CheongB.E. PhylanodifloraL. Extracts ınduce apoptosis and cell cycle arrest in human breast cancer cell line, MCF-7.Nutr. Cancer201971466867510.1080/01635581.2018.1559942 30663402
     [Google Scholar]
  13. LiX. QuL. DongY. HanL. LiuE. FangS. ZhangY. WangT. A review of recent research progress on the astragalus genus.Molecules20141911188501888010.3390/molecules191118850 25407722
     [Google Scholar]
  14. ChenJ.C. ChiuM.H. NieR.L. CordellG.A. QiuS.X. Cucurbitacins and cucurbitane glycosides: structures and biological activities.Nat. Prod. Rep.200522338639910.1039/b418841c 16010347
     [Google Scholar]
  15. LeeD.H. IwanskiG.B. ThoennissenN.H. Cucurbitacin: Ancient compound shedding new light on cancer treatment.ScientificWorldJournal20101041341810.1100/tsw.2010.44 20209387
     [Google Scholar]
  16. Tannin-SpitzT. GrossmanS. DovratS. GottliebH.E. BergmanM. Growth inhibitory activity of cucurbitacin glucosides isolated from Citrullus colocynthis on human breast cancer cells.Biochem. Pharmacol.2007731566710.1016/j.bcp.2006.09.012 17049494
     [Google Scholar]
  17. WakimotoN. YinD. O’KellyJ. HarituniansT. KarlanB. SaidJ. XingH. KoefflerH.P. Cucurbitacin B has a potent antiproliferative effect on breast cancer cells in vitro and in vivo.Cancer Sci.20089991793179710.1111/j.1349‑7006.2008.00899.x 18627377
     [Google Scholar]
  18. YangL. WuS. ZhangQ. LiuF. WuP. 23,24-Dihydrocucurbitacin B induces G2/M cell-cycle arrest and mitochondria-dependent apoptosis in human breast cancer cells (Bcap37).Cancer Lett.2007256226727810.1016/j.canlet.2007.06.018 17681423
     [Google Scholar]
  19. ChoudharyM.I. ZafarS. KhanN.T. AhmadS. NoreenS. MarasiniB.P. Al-KhedhairyA.A. Atta-ur-Rahman, Biotransformation of dehydroepiandrosterone with Macrophomina phaseolina and β-glucuronidase inhibitory activity of transformed products.J. Enzyme Inhib. Med. Chem.201227334835510.3109/14756366.2011.590804 21774747
     [Google Scholar]
  20. DevkotaK.P. ChoudharyM.I. NawazS.A. LannangA.M. LentaB.N. FokouP.A. SewaldN. Microbial transformation of the steroidal alkaloid dictyophlebine by Rhizopus stolonifer.Chem. Pharm. Bull. (Tokyo)200755468268410.1248/cpb.55.682 17409573
     [Google Scholar]
  21. TongW.Y. DongX. Microbial biotransformation: Recent developments on steroid drugs.Recent Pat. Biotechnol.20093214115310.2174/187220809788700157 19519569
     [Google Scholar]
  22. HenryN.L. AzzouzF. DestaZ. LiL. NguyenA.T. LemlerS. HaydenJ. TarpinianK. YakimE. FlockhartD.A. StearnsV. HayesD.F. StornioloA.M. Predictors of aromatase inhibitor discontinuation as a result of treatment-emergent symptoms in early-stage breast cancer.J. Clin. Oncol.201230993694210.1200/JCO.2011.38.0261 22331951
     [Google Scholar]
  23. WangS. LuZ. LangB. WangX. LiY. ChenJ. Curvularia lunata and curvularia leaf spot of maize in china.ACS Omega2022751474624747010.1021/acsomega.2c03013 36591195
     [Google Scholar]
  24. HouJ.M. MaB.C. ZuoY.H. GuoL.L. GaoS.G. WangY.Y. LiuT. Rapid and sensitive detection of Curvularia lunata associated with maize leaf spot based on its Clg2p gene using semi-nested PCR.Lett. Appl. Microbiol.201356424525010.1111/lam.12040 23278833
     [Google Scholar]
  25. LuY. SongY. XueZ. Multiplex polymerase chain reaction detection of Curvularia lunata, Bipolaris maydis, and Aureobasidium zeae in infected maize leaf tissues.J. Basic Microbiol.201959986286610.1002/jobm.201900185 31330054
     [Google Scholar]
  26. PatilB.B. ChincholkarS. Influence of substrate preparation method on rifamycin oxidase activity of C. lunata.Indian J. Exp. Biol.199735917919
     [Google Scholar]
  27. HeS. OuR. WangW. JiL. GaoH. ZhuY. LiuX. ZhengH. LiuZ. WuP. LuL. Camptosorus sibiricus rupr aqueous extract prevents lung tumorigenesis via dual effects against ROS and DNA damage.J. Ethnopharmacol.2018220445610.1016/j.jep.2017.12.021 29258855
     [Google Scholar]
  28. YuyamaK.T. FortkampD. AbrahamW.R. Eremophilane-type sesquiterpenes from fungi and their medicinal potential.Biol. Chem.20173991132810.1515/hsz‑2017‑0171 28822220
     [Google Scholar]
  29. van de LoosdrechtA.A. BeelenR.H. OssenkoppeleG.J. BroekhovenM.G. A tetrazolium based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leukemia.J. Immunol. Methods19941741-231132010.1016/0022‑1759(94)90034‑5
     [Google Scholar]
  30. AbalP. LouzaoM. AnteloA. AlvarezM. CagideE. Vilariño, N.; Vieytes, M.; Botana, L. Acute oral toxicity of tetrodotoxin in mice: Determination of lethal dose 50 (LD50) and no observed adverse effect level (NOAEL).Toxins (Basel)2017937510.3390/toxins9030075 28245573
     [Google Scholar]
  31. RossD.S. SteeleG.Jr RodrickM.L. MilfordE. BledayR.S. LaheyS.J. DeasyJ.M. RaynerA.A. WilsonR.E. The effect of 1,2‐dimethylhydrazine (DMH) carcinogenesis on peripheral T cell subsets in the wistar furth rat.J. Surg. Oncol.198426423824410.1002/jso.2930260408 6236335
     [Google Scholar]
  32. KimC.S. ChoiS.J. ParkC.Y. LiC. ChoiJ.S. Effects of silybinin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen in rats.Anticancer Res.20103017985 20150620
     [Google Scholar]
  33. ReitmanS. FrankelS. A colorimetric method for the determination of plasma oxaloacetic acid and glutamic pyruvic transaminases.Am. J. Clin. Pathol.195728566310.1093/ajcp/28.1.56 13458125
     [Google Scholar]
  34. KindP.R.N. KingE.J. Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrine.J. Clin. Pathol.19547432232610.1136/jcp.7.4.322 13286357
     [Google Scholar]
  35. BuhlS.N. JacksonK.Y. Optimal conditions, and comparison of lactate dehydrogenase catalysis of the lactate to pyruvate to lactate reactions in human plasma at 25, 30 and 37 0C.Clin. Chem.1978241582810.1093/clinchem/24.5.828 25724
     [Google Scholar]
  36. UchiyamaM. MiharaM. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test.Anal. Biochem.197886127127810.1016/0003‑2697(78)90342‑1 655387
     [Google Scholar]
  37. ChanarinI. Textbook of Laboratory Hematology: An Account of Laboratory Techniques.New YorkChurchill Livingstone1989
     [Google Scholar]
  38. MarklundS. MarklundG. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase.Eur. J. Biochem.197447346947410.1111/j.1432‑1033.1974.tb03714.x 4215654
     [Google Scholar]
  39. PagliaD.E. ValentineW.N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase.J. Lab. Clin. Med.1967701158169 6066618
     [Google Scholar]
  40. AlturkistaniH.A. TashkandiF.M. MohammedsalehZ.M. Histological stains: A literature review and case study.Glob. J. Health Sci.201583727910.5539/gjhs.v8n3p72 26493433
     [Google Scholar]
  41. PetronelliA. PannitteriG. TestaU. Triterpenoids as new promising anticancer drugs.Anticancer Drugs2009201088089210.1097/CAD.0b013e328330fd90 19745720
     [Google Scholar]
  42. Garcia-GranadosA. MartinezA. ParraA. RivasF. Manoyl-oxide biotransformations with filamentous fungi.Curr. Org. Chem.200711867969210.2174/138527207780598774
     [Google Scholar]
  43. ArantesS. HansonJ. The biotransformation of sesquiterpenoids by Mucor plumbeus.Curr. Org. Chem.200711865766310.2174/138527207780598747
     [Google Scholar]
  44. ParraA. RivasF. Garcia-GranadosA. MartinezA. Microbial transformation of triterpenoids.Mini Rev. Org. Chem.20096430732010.2174/157019309789371569
     [Google Scholar]
  45. ChangtamC. SukcharoenO. YingyongnarongkulB. ChimnoiN. SuksamrarnA. Functional group-mediated biotransformation by Curvularia lunata NRRL 2178: Synthesis of 3-dehydro-2-deoxy-ecdysteroids from the 3-hydroxy-2-mesyloxy analogues.Tetrahedron200864112626263310.1016/j.tet.2008.01.033
     [Google Scholar]
  46. TangY. LiW. CaoJ. LiW. ZhaoY. Bioassay-guided isolation and identification of cytotoxic compounds from Bolbostemma paniculatum.J. Ethnopharmacol.2015169182310.1016/j.jep.2015.04.003 25882313
     [Google Scholar]
  47. JiangH. TanR. JiaoR. DengX. TanR. Herpecaudin from Herpetospermum caudigerum, a xanthine oxidase inhibitor with a novel isoprenoid scaffold.Planta Med.20168211/121122112710.1055/s‑0042‑108210 27272398
     [Google Scholar]
  48. ChengA.C. HsuY.C. TsaiC.C. The effects of cucurbitacin E on GADD45β‐trigger G2/M arrest and JNK‐independent pathway in brain cancer cells.J. Cell. Mol. Med.20192353512351910.1111/jcmm.14250 30912292
     [Google Scholar]
  49. HsuY-C. ChenM-J. HuangT-Y. Inducement of mitosis delay by cucurbitacin E, a novel tetracyclic triterpene from climbing stem of Cucumis melo L., through GADD45γ in human brain malignant glioma (GBM) 8401 cells.Cell Death Dis.201452e108710.1038/cddis.2014.22 24577085
     [Google Scholar]
  50. BorikR.M. HusseinM.A. Synthesis, molecular docking, biological potentials and structure-activity relationship of new quinazoline and quinazoline-4-one derivatives.Asian J. Chem.202133242343810.14233/ajchem.2021.23036
     [Google Scholar]
  51. BoshraS.A. HusseinM.A. Cranberry extract as a supplemented food in treatment of oxidative stress and breast cancer induced by N-Methyl-N-Nitrosourea in female virgin rats.Int. J. Phytomed.20168217227
     [Google Scholar]
  52. HusseinM.A. BorikR.M. A novel quinazoline-4-one derivatives as a promising cytokine inhibitor: Synthesis, molecular docking, and structure-activity relationship.Curr. Pharm. Biotechnol.20222391179120310.2174/1389201022666210601170650 34077343
     [Google Scholar]
  53. MostafaM.M. AminM.M. ZakariaM.Y. HusseinM.A. ShamaaM.M. Abd El-HalimS.M. Chitosan surface-modified PLGA nanoparticles loaded with cranberry powder extract as a potential oral delivery platform for targeting colon cancer cells.Pharmaceutics202315260610.3390/pharmaceutics15020606 36839928
     [Google Scholar]
  54. SonpavdeG. PondG.R. BerryW.R. de WitR. ArmstrongA.J. EisenbergerM.A. TannockI.F. Serum alkaline phosphatase changes predict survival independent of PSA changes in men with castration-resistant prostate cancer and bone metastasis receiving chemotherapy.Urol. Oncol.201230560761310.1016/j.urolonc.2010.07.002 20888271
     [Google Scholar]
  55. ChungS.O. KimY.J. ParkS.U. An updated review of Cucurbitacins and their biological and pharmacological activities.EXCLI J.20151456256610.17179/excli2015‑283 26648815
     [Google Scholar]
  56. LuJ. DingT. QinX. LiuM. WangX. In vitro and in vivo evaluation of cucurbitacin E on rat hepatic CYP2C11 expression and activity using LC-MS/MS.Sci. China Life Sci.201760221522410.1007/s11427‑015‑4911‑7 26354504
     [Google Scholar]
  57. XieH. TuoX. ZhangF. BowenL. ZhaoW. XuY. Dietary cucurbitacin e reduces high-strength altitude training induced oxidative stress, inflammation and immunosuppression.Acad. Bras. Cienc.2020924e20200012
     [Google Scholar]
  58. M Soliman, S.; Mosallam, S.; Mosallam, S.; Mamdouh, M.A.; Hussein, M.A.; M Abd El-Halim, S. Design and optimization of cranberry extract loaded bile salt augmented liposomes for targeting of MCP-1/STAT3/VEGF signaling pathway in DMN-intoxicated liver in rats.Drug Deliv.202229142743910.1080/10717544.2022.2032875 35098843
     [Google Scholar]
  59. ArulkumaranS. RamprasathV.R. ShanthiP. SachdanandamP. Alteration of DMBA-induced oxidative stress by additive action of a modified indigenous preparation-Kalpaamruthaa.Chem. Biol. Interact.200716729910610.1016/j.cbi.2007.01.013 17349985
     [Google Scholar]
  60. HusseinM.A. BorikR.M. A novel quinazoline-4-one derivatives as a promising cytokine inhibitors: Synthesis, molecular docking, and structure-activity relationship.Curr. Pharm. Biotechnol.20222391179120310.2174/1389201022666210601170650 34077343
     [Google Scholar]
  61. El-GizawyH.A. HusseinM.A. Fatty acids profile, nutritional values, anti-diabetic and antioxidant activity of the fixed oil of malvaparviflora growing in Egypt.Int. J. Phytomed.20157219230
     [Google Scholar]
  62. AhnJ. XiaT. KonnoH. KonnoK. RuizP. BarberG.N. Inflammation-driven carcinogenesis is mediated through STING.Nat. Commun.201451516610.1038/ncomms6166 25300616
     [Google Scholar]
  63. MosaadY.O. HusseinM.A. AteyyaH. MohamedA.H. AliA.A. Ramadan YoussufA. WinkM. El-KholyA.A. Vanin 1 gene role in modulation of iNOS/MCP-1/TGF-β1 signaling pathway in obese diabetic patients.J. Inflamm. Res.2022156745675910.2147/JIR.S386506 36540060
     [Google Scholar]
  64. ZhongH. HuangY. DengX. LiuM. LuoW. CucurbitacinB. Cucurbitacin B supplementation reduces inflammatory responses and alveolar bone loss via regulating MPO, COX-2 and RANK/RANKL/OPG signals in a rodent model of ligature-induced periodontitis.J. King Saud Univ. Sci.20203231889189510.1016/j.jksus.2020.01.028
     [Google Scholar]
  65. SongH. WangY. LiL. SuiH. WangP. WangF. CucurbitacinE. Cucurbitacin E inhibits proliferation and migration of intestinal epithelial cells via activating cofilin.Front. Physiol.20189109010.3389/fphys.2018.01090 30131725
     [Google Scholar]
  66. DeS. SarkarB. JadhavG.R. RamasamyS.K. BanerjeeS. MoorthyA. PairaP. K, A.K.S. Experimental and theoretical study on the biomolecular interaction of novel acenaphtho quinoxaline and dipyridophenazine analogues.ChemistrySelect2018338105931060210.1002/slct.201801448
     [Google Scholar]
  67. KuoY.C. YenM.H. DeS. RajeshR. TaiC.K. Optimized lipopolymers with curcumin to enhance AZD5582 and GDC0152 activity and downregulate inhibitors of apoptosis proteins in glioblastoma multiforme.Biomaterials Advances202315421363910.1016/j.bioadv.2023.213639 37793310
     [Google Scholar]
  68. KuoY.C. LinS.Y. DeS. RajeshR. Regeneration of pancreatic cells using optimized nanoparticles and L-glutamic acid-gelatin scaffolds with controlled topography and grafted activin A/BMP4.ACS Biomater. Sci. Eng.20239116208622410.1021/acsbiomaterials.3c00791 37882705
     [Google Scholar]
  69. DeS. Ashok KumarS.K. Development of highly potent Arene-Ru (II)-ninhydrin complexes for inhibition of cancer cell growth.Inorg. Chim. Acta202050811964110.1016/j.ica.2020.119641
     [Google Scholar]
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Cucurbitacin-E; Curvularia lunata Secondary Metabolite as a BRCA 1 and 2 Regulator in Mice Associated Breast Cancer
Curr. Bioact. Compd. 21, e15734072319208 (2025); https://doi.org/10.2174/0115734072319208240928142003
/content/journals/cbc/10.2174/0115734072319208240928142003
/content/journals/cbc/10.2174/0115734072319208240928142003
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  • Article Type:     Research Article
Keyword(s): BRCA1 and BRCA2; Cucurbitacin-E; Curvularia lunata; DMBA; MCF-7; P53

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