Skip to content
2000
Volume 33, Issue 7
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Aerobic glycolysis is crucial for cancer cells to survive, grow, and progress. In the current study, the anti-cancer effects of astragalin (ASG) on breast cancer cells and in the glycolytic pathway through AMPK/mTOR have been evaluated.

Objective

The objective of this study was to examine the impact of ASG, a natural flavonoid, on glycolysis targeting signalling in MDA-MB-231 breast cancer cells.

Methods

The study utilized ASG, which was isolated from The cells were treated with different concentrations of ASG (20 and 40 µg/mL), and anti-glycolytic activities were measured through cell proliferation, expression of glycolytic enzymes (), glucose uptake, and lactate concentration assays. The MTT assay was used to assess cellular proliferation, while the glucose uptake and lactate levels were determined by employing colorimetric assays. The mRNA expression of target glycolytic enzymes was determined by qRT-PCR. The protein levels of glycolytic targets, as well as that of and were determined by western blot. docking of ASG was done with and proteins.

Results

Astragalin exhibited dose- and time-dependent anti-proliferative effects in MDA-MB-231 cells. In breast cancer cells, the mRNA and protein expression of , , and were all significantly downregulated after receiving ASG treatments. Furthermore, after ASG treatments, MDA-MB231 cells showed a significant decrease in lactate and glucose uptake compared to control cells. Mechanistically, ASG increased activation and suppressed activation in these cells. The inhibitory role of ASG on aerobic glycolysis was prevented by treatments with compound C (an inhibitor). However, combined treatment of compound C and ASG could nullify the ASG-induced anti-glycolysis effect and restore the level of p-AMPK and in MDA-MB231 cells. The results from molecular docking predicted that ASG had the potential to bind and with free energy for binding, -8.2 kcal/mol and -8.1 kcal/mol, respectively.

Conclusion

Taken together, the findings from this study indicated that ASG might modulate the pathway to inhibit aerobic glycolysis and proliferation of MDA-MB231 breast cancer.

© 2026 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673304759240722064518
2024-07-25
2026-02-26

  • From This Site

    /content/journals/cmc/10.2174/0109298673304759240722064518
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. OngS.K. HaruyamaR. YipC.H. NganT.T. LiJ. LaiD. ZhangY. YiS. ShankarA. SuzannaE. JungS.Y. Feasibility of monitoring global breast cancer initiative framework key performance indicators in 21 asian national cancer centers alliance member countries.EClinicalMedicine20236710236510.1016/j.eclinm.2023.102365
     [Google Scholar]
  2. GuestiniF. McNamaraK.M. IshidaT. SasanoH. Triple negative breast cancer chemosensitivity and chemoresistance: current advances in biomarkers indentification.Expert Opin. Ther. Targets201620670572010.1517/14728222.2016.112546926607563
     [Google Scholar]
  3. GarmpisN. DamaskosC. GarmpiA. NikolettosK. DimitroulisD. DiamantisE. FarmakiP. PatsourasA. VoutyritsaE. SyllaiosA. Molecular classification and future therapeutic challenges of triple-negative breast cancer.In Vivo20203441715172710.21873/invivo.11965
     [Google Scholar]
  4. O’TooleS.A. BeithJ.M. MillarE.K.A. WestR. McLeanA. CazetA. SwarbrickA. OakesS.R. Therapeutic targets in triple negative breast cancer.J. Clin. Pathol.201366653054210.1136/jclinpath‑2012‑20136123436929
     [Google Scholar]
  5. TungmunnithumD. PinthongD. HanoC. Flavonoids from Nelumbo nucifera Gaertn., a medicinal plant: Uses in traditional medicine, phytochemistry and pharmacological activities.Medicines (Basel)20185412710.3390/medicines504012730477094
     [Google Scholar]
  6. AtanasovA.G. WaltenbergerB. Pferschy-WenzigE.M. LinderT. WawroschC. UhrinP. TemmlV. WangL. SchwaigerS. HeissE.H. RollingerJ.M. SchusterD. BreussJ.M. BochkovV. MihovilovicM.D. KoppB. BauerR. DirschV.M. StuppnerH. Discovery and resupply of pharmacologically active plant-derived natural products: A review.Biotechnol. Adv.20153381582161410.1016/j.biotechadv.2015.08.00126281720
     [Google Scholar]
  7. CraggG.M. PezzutoJ.M. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents.Med. Princ. Pract.201625Suppl 2Suppl. 2415910.1159/00044340426679767
     [Google Scholar]
  8. AbdelgaleilS.A.M. SaadM.M.G. ArieftaN.R. ShionoY. Antimicrobial and phytotoxic activities of secondary metabolites from Haplophyllum tuberculatum and Chrysanthemum coronarium.S. Afr. J. Bot.2020128354110.1016/j.sajb.2019.10.005
     [Google Scholar]
  9. Al-BurtamaniS.K.S. FatopeM.O. MarwahR.G. OnifadeA.K. Al-SaidiS.H. Chemical composition, antibacterial and antifungal activities of the essential oil of Haplophyllum tuberculatum from Oman.J. Ethnopharmacol.2005961-210711210.1016/j.jep.2004.08.03915588657
     [Google Scholar]
  10. UlubelenA. ÖztürkM. Alkaloids, coumarins and lignans from Haplophyllum species.Rec. Nat. Prod.2008235469
     [Google Scholar]
  11. KhalidS. WatermanP. Alkaloid, lignan and flavonoid constituents of Haplophyllum tuberculatum from Sudan.Planta Med.1981431014815210.1055/s‑2007‑97149117402027
     [Google Scholar]
  12. YuldashevM.P. Flavonoids and coumarins of Haplophyllum leptomerum and H. dubium. Chem. Nat. Compd.200238219219310.1023/A:1019608502696
     [Google Scholar]
  13. HamdiA. VianeJ. MahjoubM.A. MajouliK. GadM.H.H. KharbachM. DemeyerK. MarzoukZ. HeydenY.V. Polyphenolic contents, antioxidant activities and UPLC–ESI–MS analysis of Haplophyllum tuberculatum A. Juss leaves extracts.Int. J. Biol. Macromol.20181061071107910.1016/j.ijbiomac.2017.08.10728851641
     [Google Scholar]
  14. RiazA. RasulA. HussainG. ZahoorM.K. JabeenF. SubhaniZ. YounisT. AliM. SarfrazI. SelamogluZ. Astragalin: A bioactive phytochemical with potential therapeutic activities.Adv. Pharmacol. Sci.2018201811510.1155/2018/979462529853868
     [Google Scholar]
  15. AhmedH. MoawadA. OwisA. AbouZidS. AhmedO. Flavonoids of Calligonum polygonoides and their cytotoxicity.Pharm. Biol.201654102119212610.3109/13880209.2016.114677826922854
     [Google Scholar]
  16. TianS. WeiY. HuH. ZhaoH. Mixed computational- experimental study to reveal the anti-metastasis and anti-angiogenesis effects of Astragalin in human breast cancer.Comput. Biol. Med.202215010613110.1016/j.compbiomed.2022.10613136195046
     [Google Scholar]
  17. SchwartzL. SupuranT. Warburg effect in colorectal cancer: The emerging roles in tumor microenvironment and therapeutic implications.J Hematol Oncol202215116010.1186/s13045‑022‑01358‑5
     [Google Scholar]
  18. SchiliroC. FiresteinB.L. Mechanisms of metabolic reprogramming in cancer cells supporting enhanced growth and proliferation.Cells2021105105610.3390/cells1005105633946927
     [Google Scholar]
  19. FengJ. LiJ. WuL. YuQ. JiJ. WuJ. DaiW. GuoC. Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma.J. Exp. Clin. Cancer Res.202039112610.1186/s13046‑020‑01629‑432631382
     [Google Scholar]
  20. ParkJ.H. PyunW.Y. ParkH.W. Cancer metabolism: Phenotype, signaling and therapeutic targets.Cells2020910230810.3390/cells910230833081387
     [Google Scholar]
  21. ZhangY. LiQ. HuangZ. LiB. NiceE.C. HuangC. WeiL. ZouB. Targeting glucose metabolism enzymes in cancer treatment: Current and emerging strategies.Cancers (Basel)20221419456810.3390/cancers1419456836230492
     [Google Scholar]
  22. GhanavatM. ShahrouzianM. Deris ZayeriZ. BanihashemiS. KazemiS.M. SakiN. Digging deeper through glucose metabolism and its regulators in cancer and metastasis.Life Sci.202126411860310.1016/j.lfs.2020.11860333091446
     [Google Scholar]
  23. VargheseE. SamuelS.M. LíškováA. SamecM. KubatkaP. BüsselbergD. Targeting glucose metabolism to overcome resistance to anticancer chemotherapy in breast cancer.Cancers (Basel)2020128225210.3390/cancers1208225232806533
     [Google Scholar]
  24. FanH. WuY. YuS. LiX. WangA. WangS. ChenW. LuY. Critical role of mTOR in regulating aerobic glycolysis in carcinogenesis (Review).Int. J. Oncol.202058191910.3892/ijo.2020.515233367927
     [Google Scholar]
  25. HuM. ChenX. MaL. MaY. LiY. SongH. XuJ. ZhouL. LiX. JiangY. KongB. HuangP. AMPK inhibition suppresses the malignant phenotype of pancreatic cancer cells in part by attenuating aerobic glycolysis.J. Cancer20191081870187810.7150/jca.2829931205544
     [Google Scholar]
  26. LiW. SaudS.M. YoungM.R. ChenG. HuaB. Targeting AMPK for cancer prevention and treatment.Oncotarget20156107365737810.18632/oncotarget.362925812084
     [Google Scholar]
  27. DemirganR. KaragözA. PekmezM. Önay-UçarE. ArtunF.T. GürerÇ. MatA. In vitro anticancer activity and cytotoxicity of some papaver alkaloids on cancer and normal cell lines.Afr. J. Tradit. Complement. Altern. Med.2016133222610.4314/ajtcam.v13i3.3
     [Google Scholar]
  28. LavoieS. CôtéI. PichetteA. GauthierC. OuelletM. Nagau-LavoieF. MshvildadzeV. LegaultJ. Chemical composition and anti-herpes simplex virus type 1 (HSV-1) activity of extracts from Cornus canadensis. BMC Complement. Altern. Med.201717112310.1186/s12906‑017‑1618‑228228101
     [Google Scholar]
  29. HashimY. ToumeK. MizukamiS. GeY.W. TaniguchiM. TeklemichaelA.A. HuyN.T. BodiJ.M. HirayamaK. KomatsuK. Phenylpropanoid conjugated iridoids with anti-malarial activity from the leaves of Morinda morindoides. J. Nat. Med.202175491592510.1007/s11418‑021‑01541‑x34189715
     [Google Scholar]
  30. LichotaA. GwozdzinskiK. Anticancer activity of natural compounds from plant and marine environment.Int. J. Mol. Sci.20181911353310.3390/ijms1911353330423952
     [Google Scholar]
  31. HuangM. LuJ.J. DingJ. Natural products in cancer therapy: Past, present and future.Nat. Prod. Bioprospect.202111151310.1007/s13659‑020‑00293‑733389713
     [Google Scholar]
  32. BaeK. JinW. ThuongP.T. MinB.S. NaM. LeeY.M. KangS.S. A new flavonoid glycoside from the leaf of Cephalotaxus koreana.Fitoterapia200778640941310.1016/j.fitote.2007.02.00817616262
     [Google Scholar]
  33. YangJ.H. KondratyukT.P. MarlerL.E. QiuX. ChoiY. CaoH. YuR. SturdyM. PeganS. LiuY. WangL.Q. MesecarA.D. BreemenR.B.V. PezzutoJ.M. FongH.H.S. ChenY.G. ZhangH.J. Isolation and evaluation of kaempferol glycosides from the fern Neocheiropteris palmatopedata. Phytochemistry2010715-664164710.1016/j.phytochem.2010.01.00220100622
     [Google Scholar]
  34. FadakaA. AjiboyeB. OjoO. AdewaleO. OlayideI. EmuowhochereR. Biology of glucose metabolization in cancer cells.J Oncol Sci201732455110.1016/j.jons.2017.06.002
     [Google Scholar]
  35. ReckzehE.S. KarageorgisG. SchwalfenbergM. CeballosJ. NowackiJ. StroetM.C. BiniciA. KnauerL. BrandS. ChoidasA. Inhibition of glucose transporters and glutaminase synergistically impairs tumor cell growth.Cell Chem. Biol.201926912141228.e2510.1016/j.chembiol.2019.06.005
     [Google Scholar]
  36. AndersonM. MarayatiR. MoffittR. YehJ.J. Hexokinase 2 promotes tumor growth and metastasis by regulating lactate production in pancreatic cancer.Oncotarget2017834560815609410.18632/oncotarget.976028915575
     [Google Scholar]
  37. LiW.C. HuangC.H. HsiehY.T. ChenT.Y. ChengL.H. ChenC.Y. LiuC.J. ChenH.M. HuangC.L. LoJ.F. ChangK.W. Regulatory role of hexokinase 2 in modulating head and neck tumorigenesis.Front. Oncol.20201017610.3389/fonc.2020.0017632195170
     [Google Scholar]
  38. CaiH. LiJ. ZhangY. LiaoY. ZhuY. WangC. HouJ. LDHA promotes oral squamous cell carcinoma progression through facilitating glycolysis and epithelial–mesenchymal transition.Front. Oncol.20199144610.3389/fonc.2019.0144631921691
     [Google Scholar]
  39. Abdel-WahabA.F. MahmoudW. Al-HarizyR.M. Targeting glucose metabolism to suppress cancer progression: Prospective of anti-glycolytic cancer therapy.Pharmacol. Res.201915010451110.1016/j.phrs.2019.10451131678210
     [Google Scholar]
  40. AlvesA.P. MamedeA.C. AlvesM.G. OliveiraP.F. RochaS.M. BotelhoM.F. MaiaC.J. Glycolysis inhibition as a strategy for hepatocellular carcinoma treatment?Curr. Cancer Drug Targets2018191264010.2174/156800961866618043014444129749314
     [Google Scholar]
  41. LiW. HaoJ. ZhangL. ChengZ. DengX. ShuG. Astragalin reduces hexokinase 2 through increasing mir-125b to inhibit the proliferation of hepatocellular carcinoma cells in vitro and in vivo.J. Agric. Food Chem.201765295961597210.1021/acs.jafc.7b0212028654261
     [Google Scholar]
  42. SongL. FuQ. Study of the effect of astragalin on proliferation of ovarian cancer cells by inhibiting the glycolytic pathway induced via HIF-1α.Pract. Oncol. J.20186503509
     [Google Scholar]
  43. SongG. FangJ. ShangC. LiY. ZhuY. XiuZ. SunL. JinN. LiX. Adapoptin inhibits glycolysis, migration and invasion in lung cancer cells targeting AMPK/mTOR signaling pathway.Exp. Cell Res.2021409211292610.1016/j.yexcr.2021.11292634793774
     [Google Scholar]
  44. ChoA.R. ParkW.Y. LeeH.J. SimD.Y. ImE. ParkJ.E. AhnC.H. ShimB.S. KimS.H. Antitumor effect of morusin via G1 arrest and antiglycolysis by AMPK activation in hepatocellular cancer.Int. J. Mol. Sci.202122191061910.3390/ijms22191061934638959
     [Google Scholar]
  45. HuangX. LiX. XieX. YeF. ChenB. SongC. TangH. XieX. High expressions of LDHA and AMPK as prognostic biomarkers for breast cancer.Breast201630394610.1016/j.breast.2016.08.01427598996
     [Google Scholar]
  46. FaubertB. BoilyG. IzreigS. GrissT. SamborskaB. DongZ. DupuyF. ChambersC. FuerthB.J. ViolletB. MamerO.A. AvizonisD. DeBerardinisR.J. SiegelP.M. JonesR.G. AMPK is a negative regulator of the Warburg effect and suppresses tumor growth in vivo.Cell Metab.201317111312410.1016/j.cmet.2012.12.00123274086
     [Google Scholar]
  47. LiS. LiY. HuR. LiW. QiuH. CaiH. WangS. The mTOR inhibitor AZD8055 inhibits proliferation and glycolysis in cervical cancer cells.Oncol. Lett.20135271772110.3892/ol.2012.105823420667
     [Google Scholar]
  48. KubinyiH. Hydrogen bonding: The last mystery in drug design?Seman. Sch.200110.1002/9783906390437.ch28
     [Google Scholar]
  49. BulusuG. DesirajuG.R. Strong and weak hydrogen bonds in protein–ligand recognition.J. Indian Inst. Sci.20201001314110.1007/s41745‑019‑00141‑9
     [Google Scholar]
  50. OgboyeR.M. PatilR.B. FamuyiwaS.O. FaloyeK.O. Novel α-amylase and α-glucosidase inhibitors from selected Nigerian antidiabetic plants: An in silico approach.J. Biomol. Struct. Dyn.202240146340634910.1080/07391102.2021.188348033583331
     [Google Scholar]
  51. NoureddineO. IssaouiN. MedimaghM. Al-DossaryO. MarouaniH. Quantum chemical studies on molecular structure, AIM, ELF, RDG and antiviral activities of hybrid hydroxychloroquine in the treatment of COVID-19: Molecular docking and DFT calculations.J. King. Saud Univ. Sci202133210133410.1016/j.jksus.2020.101334
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673304759240722064518
Loading
Exploring the Anticancer Potential of Astragalin in Triple Negative Breast Cancer Cells by Attenuating Glycolytic Pathway through AMPK/mTOR
Curr. Med. Chem. 33, 1405 (2026); https://doi.org/10.2174/0109298673304759240722064518
/content/journals/cmc/10.2174/0109298673304759240722064518
/content/journals/cmc/10.2174/0109298673304759240722064518
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): AMPK; Astragalin; breast cancer; glycolysis; lactate; mTOR

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