Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Biotechnology
  4. Volume 13, Issue 4
  5. Article
Volume 13, Issue 4
  • ISSN: 2211-5501
  • E-ISSN: 2211-551X

Abstract

Introduction

Cancer is the uncontrolled proliferation of cells leading to metastasis due to genetic alterations resulting in oncogenes activation and tumor suppressor genes deactivation. It is the 2nd leading cause of death across the world. MMP-9 or gelatinase B, plays an effective role in ECM degradation, normal tissue turnover, and tissue remodelling. Overexpression of MMP-9 has been studied in almost all types of cancers proving the effective role of MMP-9 in accelerating malignant conditions. Thus, targeting MMP-9 to treat cancer seems to be a potential strategy to deal with adverse pathologies of cancer. Chemotherapy and radiotherapy are frequently utilized for the treatment of cancer but are associated with diverse side effects. Flavonoids are natural compounds frequently found in plants and have been analysed for the structural inhibition potential against MMP-9 by several researchers to develop natural treatments against cancer, but none of the flavonoids have landed into clinical use.

Methods

In the present study, in-depth analysis to investigate the synergistic effects of flavonoids for structural inhibition of MMP-9 was done.

Results

The ADMET and bioactive properties analysis revealed effective drug-like properties of the considered flavonoids. Principal component analysis of ADMET and bioactive properties revealed high similarity in the chemical nature of luteolin and quercetin. Molecular docking analysis of MMP-9 with the considered flavonoids individually revealed the highest effective binding energy of luteolin. Combination docking analysis of MMP-9 with different combinations of flavonoids led to the identification of two combinations including Quercetin with Genistein and Luteolin and Genistein revealing high negative binding energies of -15.48kcal/mol and -15.31kcal/mol which were significantly greater than the binding energies identified for respective ligands in individual dockings.

Conclusion

Thus, the present study put forward synergistic natural flavonoid combinations against cancer the MMP-9 inhibition approach that can be further evaluated to develop high-efficacy treatments.

© 2024 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cbiot/10.2174/0122115501324502240919104816
2024-09-30
2025-01-19

  • From This Site

    /content/journals/cbiot/10.2174/0122115501324502240919104816
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. MathurP. SathishkumarK. ChaturvediM. DasP. StephenS. Cancer incidence estimates for 2022 & projection for 2025: Result from National Cancer Registry Programme, India.Indian J. Med. Res.2022156459860710.4103/ijmr.ijmr_1821_2236510887
     [Google Scholar]
  2. KapoorC. VaidyaS. WadhwanV. Hitesh KaurG. PathakA. Seesaw of matrix metalloproteinases (MMPs).J. Cancer Res. Ther.2016121283510.4103/0973‑1482.15733727072206
     [Google Scholar]
  3. MondalS. AdhikariN. BanerjeeS. AminS.A. JhaT. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview.Eur. J. Med. Chem.202019411226010.1016/j.ejmech.2020.11226032224379
     [Google Scholar]
  4. XiaoJ. HuangJ. YolkenR. H. Elevated matrix Metalloproteinase-9 associated with reduced cerebellar perineuronal nets in female mice with toxoplasmosis.Brain Behav Immun Health20243610072810.1016/j.bbih.2024.100728
     [Google Scholar]
  5. RashidZ.A. BardaweelS.K. Novel Matrix Metalloproteinase-9 (MMP-9) Inhibitors in Cancer Treatment.Int. J. Mol. Sci.202324151213310.3390/ijms24151213337569509
     [Google Scholar]
  6. HsuC.C. HuangS.F. WangJ.S. ChuW.K. NienJ.E. ChenW.S. ChowS.E. Interplay of N-Cadherin and matrix metalloproteinase 9 enhances human nasopharyngeal carcinoma cell invasion.BMC Cancer201616180010.1186/s12885‑016‑2846‑427737648
     [Google Scholar]
  7. VafadariB. SalamianA. KaczmarekL. MMP-9 in translation: From molecule to brain physiology, pathology, and therapy.J. Neurochem.2016139S29111410.1111/jnc.1341526525923
     [Google Scholar]
  8. HannocksM.J. ZhangX. GerwienH. ChashchinaA. BurmeisterM. KorposE. SongJ. SorokinL. The gelatinases, MMP-2 and MMP-9, as fine tuners of neuroinflammatory processes.Matrix Biol.201975-7610211310.1016/j.matbio.2017.11.00729158162
     [Google Scholar]
  9. HuangH. Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances.Sensors (Basel)20181810324910.3390/s1810324930262739
     [Google Scholar]
  10. LiH. QiuZ. LiF. WangC. The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis.Oncol. Lett.20171455865587010.3892/ol.2017.692429113219
     [Google Scholar]
  11. AkterH. ParkM. KwonO.S. SongE.J. ParkW.S. KangM.J. Activation of matrix metalloproteinase-9 (MMP-9) by neurotensin promotes cell invasion and migration through ERK pathway in gastric cancer.Tumour Biol.20153686053606210.1007/s13277‑015‑3282‑925724188
     [Google Scholar]
  12. AminS.A. AdhikariN. JhaT. Is dual inhibition of metalloenzymes HDAC-8 and MMP-2 a potential pharmacological target to combat hematological malignancies?Pharmacol. Res.201712281910.1016/j.phrs.2017.05.00228501516
     [Google Scholar]
  13. Jabłońska-TrypućA. MatejczykM. RosochackiS. Jabłon´A.J. Trypuc´J-T. Matrix metalloproteinases (MMPs), the main extracellular matrix (ECM) enzymes in collagen degradation, as a target for anticancer drugs.J. Enzyme Inhib. Med. Chem.201631sup117718310.3109/14756366.2016.116162027028474
     [Google Scholar]
  14. HouH. ZhangG. WangH. GongH. WangC. ZhangX. High matrix metalloproteinase-9 expression induces angiogenesis and basement membrane degradation in stroke-prone spontaneously hypertensive rats after cerebral infarction.Neural Regen Res201491111546210.4103/1673‑5374.135318
     [Google Scholar]
  15. MiskoA. FergusonT. NotterpekL. Matrix metalloproteinase mediated degradation of basement membrane proteins in Trembler J neuropathy nerves.J. Neurochem.200283488589410.1046/j.1471‑4159.2002.01200.x12421361
     [Google Scholar]
  16. NiuJ. GuX. TurtonJ. MeldrumC. HowardE.W. AgrezM. Integrin-mediated signalling of gelatinase B secretion in colon cancer cells.Biochem. Biophys. Res. Commun.1998249128729110.1006/bbrc.1998.91289705874
     [Google Scholar]
  17. HiratsukaS. NakamuraK. IwaiS. MurakamiM. ItohT. KijimaH. ShipleyJ.M. SeniorR.M. ShibuyaM. MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis.Cancer Cell20022428930010.1016/S1535‑6108(02)00153‑812398893
     [Google Scholar]
  18. NyormoiO. MillsL. Bar-EliM. An MMP-2/MMP-9 inhibitor, 5a, enhances apoptosis induced by ligands of the TNF receptor superfamily in cancer cells.Cell Death Differ.200310555856910.1038/sj.cdd.440120912728254
     [Google Scholar]
  19. RathodS. ShindeK. PorlekarJ. ChoudhariP. DhavaleR. MahuliD. TamboliY. BhatiaM. HavalK.P. Al-SehemiA.G. PanniparaM. Computational Exploration of Anti-cancer Potential of Flavonoids against Cyclin-Dependent Kinase 8: An in silico Molecular Docking and Dynamic Approach.ACS Omega20238139140910.1021/acsomega.2c0483736643495
     [Google Scholar]
  20. Rajiv GandhiG. SharanyaC.S. JayanandanA. HaridasM. Edwin HillaryV. Rajiv GandhiS. SridharanG. SivasubramanianR. Silva VasconcelosA.B. MontalvãoM.M. Antony CeasarS. SousaN.F. ScottiL. ScottiM.T. GurgelR.Q. Quintans-JúniorL.J. Multitargeted molecular docking and dynamics simulation studies of flavonoids and volatile components from the peel of Citrus sinensis L. (Osbeck) against specific tumor protein markers.J. Biomol. Struct. Dyn.20244263051308010.1080/07391102.2023.221206237203996
     [Google Scholar]
  21. KumariS. KumarP. Design and Computational Analysis of an MMP9 Inhibitor in Hypoxia-Induced Glioblastoma Multiforme.ACS Omega2023811105651059010.1021/acsomega.3c0044136969457
     [Google Scholar]
  22. De ForniD. PoddesuB. CugiaG. ChafouleasJ. LisziewiczJ. LoriF. Synergistic drug combinations designed to fully suppress SARS-CoV-2 in the lung of COVID-19 patients.PLoS One20221711e027675110.1371/journal.pone.027675136355808
     [Google Scholar]
  23. GuptaA. ChauhanS.S. GaurA.S. ParthasarathiR. Computational screening for investigating the synergistic regulatory potential of drugs and phytochemicals in combination with 2-deoxy-D-glucose against SARS-CoV-2.Struct. Chem.20223362179219310.1007/s11224‑022‑02049‑036093277
     [Google Scholar]
  24. WiraswatiH. BashariM. AlfarafisaN. Ma’rufI. SholikhahE. WahyuningsihT. SatriyoP. MustofaM. SatriaD. DamayantiE. Pyrazoline B-Paclitaxel or Doxorubicin Combination Drugs Show Synergistic Activity Against Cancer Cells: in silico Study.Adv. Appl. Bioinform. Chem.202417334610.2147/AABC.S45228138435441
     [Google Scholar]
  25. AjjiP.K. WalderK. PuriM. Combination of Balsamin and Flavonoids Induce Apoptotic Effects in Liver and Breast Cancer Cells.Front. Pharmacol.20201157449610.3389/fphar.2020.57449633192517
     [Google Scholar]
  26. DainaA. MichielinO. ZoeteV. SwissADME: A free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.Sci. Rep.2017714271710.1038/srep4271728256516
     [Google Scholar]
  27. BanerjeeP. EckertA.O. SchreyA.K. PreissnerR. ProTox-II: A webserver for the prediction of toxicity of chemicals.Nucleic Acids Res.201846W1W257W26310.1093/nar/gky31829718510
     [Google Scholar]
  28. RaghavendraS. Aditya RaoS. J. KumarV. RameshC. K. Multiple ligand simultaneous docking (MLSD): A novel approach to study the effect of inhibitors on substrate binding to PPO.Comput Biol Chem20155981610.1016/j.compbiolchem.2015.09.008
     [Google Scholar]
  29. LipinskiC.A. LombardoF. DominyB.W. FeeneyP.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.Adv. Drug Deliv. Rev.2001461-332610.1016/S0169‑409X(00)00129‑011259830
     [Google Scholar]
  30. YousefE.M. TahirM.R. St-PierreY. GabouryL.A. MMP-9 expression varies according to molecular subtypes of breast cancer.BMC Cancer201414160910.1186/1471‑2407‑14‑60925151367
     [Google Scholar]
  31. ReinerA.T. TanS. AgreiterC. AuerK. Bachmayr-HeydaA. AustS. PechaN. MandorferM. PilsD. BrissonA.R. ZeillingerR. LimS.K. EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVs.Dis. Markers201720171910.1155/2017/965319428607529
     [Google Scholar]
  32. TianM. CuiY.Z. SongG.H. ZongM.J. ZhouX.Y. ChenY. HanJ.X. Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients.BMC Cancer20088124110.1186/1471‑2407‑8‑24118706098
     [Google Scholar]
  33. LiY. WuT. ZhangB. YaoY. YinG. Matrix metalloproteinase-9 is a prognostic marker for patients with cervical cancer.Med Oncol20122953394910.1007/s12032‑012‑0283‑z
     [Google Scholar]
  34. LiuN. WangX. WuH. LvX. XieH. GuoZ. WangJ. DouG. ZhangC. SunM. Computational study of effective matrix metalloproteinase 9 (MMP9) targeting natural inhibitors.Aging (Albany NY)20211319228672288210.18632/aging.20358134607974
     [Google Scholar]
  35. AdhipanditoC. F. LudjiD. P. K. S. ApriliantoE. JenieR. I. Al-NajjarB. HarionoM. Matrix metalloproteinase9 as the protein target in anti-breast cancer drug discovery: An approach by targeting hemopexin domain.Futur J Pharm Sci201910.1186/s43094‑019‑0001‑1
     [Google Scholar]
  36. HarionoM. RollandoR. KaramoyJ. HariyonoP. AtmonoM. DjohanM. WiwyW. NuwardaR. KurniawanC. SalinN. WahabH. Bioguided Fractionation of Local Plants against Matrix Metalloproteinase9 and Its Cytotoxicity against Breast Cancer Cell Models: in silico and in vitro Study.Molecules20202520469110.3390/molecules25204691
     [Google Scholar]
  37. KalvaS. Azhagiya SingamE.R. RajapandianV. SaleenaL.M. SubramanianV. Discovery of potent inhibitor for matrix metalloproteinase-9 by pharmacophore based modeling and dynamics simulation studies.J. Mol. Graph. Model.201449253710.1016/j.jmgm.2013.12.00824473069
     [Google Scholar]
  38. GaoQ. WangY. HouJ. YaoQ. ZhangJ. Multiple receptor-ligand based pharmacophore modeling and molecular docking to screen the selective inhibitors of matrix metalloproteinase-9 from natural products.J. Comput. Aided Mol. Des.201731762564110.1007/s10822‑017‑0028‑328623487
     [Google Scholar]
  39. ZhangQ. LiuS. LiZ.Y. ShangY.J. KollieL. LiangZ.S. Exploring the potential mechanisms of luteolin against ulcerative colitis and colorectal cancer via network pharmacology and molecular docking.TMR Integrativ Med202370e2302610.53388/TMRIM202307026
     [Google Scholar]
  40. ChangM. ChenS. LiC. ZhangY. ZhaoH. Exploring the bioactive compounds derived from Plumula Nelumbinis and potential targets for the treatment of non-small cell lung cancer: A network pharmacology study.J Cancer Discov202210.55976/jcd.1202219630‑48
     [Google Scholar]
  41. WuL. LinY. GaoS. WangY. PanH. WangZ. PozzoliniM. YangF. ZhangH. YangY. XiaoL. XuY. Luteolin inhibits triple-negative breast cancer by inducing apoptosis and autophagy through SGK1-FOXO3a-BNIP3 signaling.Front. Pharmacol.202314120084310.3389/fphar.2023.120084337346292
     [Google Scholar]
  42. SainA. KhamraiD. KandasamyT. NaskarD. Apigenin exerts anti-cancer effects in colon cancer by targeting HSP90AA1.J. Biomol. Struct. Dyn.202311310.1080/07391102.2023.229930538157250
     [Google Scholar]
  43. NairN.U. GreningerP. ZhangX. FriedmanA.A. AmzallagA. CortezE. SahuA.D. LeeJ.S. DasturA. EganR.K. MurchieE. CeribelliM. CrowtherG.S. BeckE. McClanaghanJ. Klump-ThomasC. BoisvertJ.L. DamonL.J. WilsonK.M. HoJ. TamA. McKnightC. MichaelS. ItkinZ. GarnettM.J. EngelmanJ.A. HaberD.A. ThomasC.J. RuppinE. BenesC.H. A landscape of response to drug combinations in non-small cell lung cancer.Nat. Commun.2023141383010.1038/s41467‑023‑39528‑937380628
     [Google Scholar]
  44. LafiZ. AlshaerW. GharaibehL. AlqudahD.A. AlQuaissiB. BashairehB. IbrahimA.A. Synergistic combination of doxorubicin with hydralazine, and disulfiram against MCF-7 breast cancer cell line.PLoS One2023189e029198110.1371/journal.pone.029198137768997
     [Google Scholar]
  45. HongD. S. MooreK. N. BendellJ. C. KarpD. D. WangJ. S. UlahannanS. V JonesS. WuW. DonohoG. P. DingY. CapenA. WangX. LinA. B. PatelM. R. Preclinical Evaluation and Phase Ib Study of Prexasertib, a CHK1 Inhibitor, and Samotolisib (LY3023414), a Dual PI3K/mTOR Inhibitor.Clin Cancer Res20212771864187410.1158/1078‑0432.CCR‑20‑3242
     [Google Scholar]
/content/journals/cbiot/10.2174/0122115501324502240919104816
Loading
Synergistic Structural Inhibition of MMP-9 by Natural Flavonoids: A Natural Combinatorial Therapy against Cancer
Curr. Biotechnol. 13, 207 (2024); https://doi.org/10.2174/0122115501324502240919104816
/content/journals/cbiot/10.2174/0122115501324502240919104816
/content/journals/cbiot/10.2174/0122115501324502240919104816
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher's website along with the published article.

file format download Download

  • Article Type:     Research Article
Keyword(s): ADMET; Cancer; docking; flavonoids; MMP-9; synergistic combinations

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