Skip to content
2000
Volume 25, Issue 13
  • ISSN: 1871-5206
  • E-ISSN: 1875-5992

Abstract

Objective

This study utilized three cell lines: normal prostate epithelial RWPE-1, androgen-dependent LNCaP, and androgen-independent PC3. We investigated the inhibitory effects of phenylboronic acid (PBA)’s inhibitory effect on cellular proliferation due to its ability to disrupt microtubule formation in prostate cancer cell lines. Additionally, this study aimed to assess the cytotoxic effects of PBA on prostate cancer cells using two-dimensional (2D) and three-dimensional (3D) cell culture models.

Methods

The IC values of PBA and colchicine were determined through viability assays in 2D and 3D models. Colony formation, proliferation, and migration assays were conducted. Immunofluorescence intensity analysis of MAPKKK proteins (ERK, JNK, p38) was performed to explore the mechanism of cellular response to PBA.

Results

The IC values were determined for each treatment group. After 48-hour of PBA treatment, migration was inhibited more effectively than with colchicine in both cancer cell lines. After 24-hour, PBA reduced colony formation and proliferation. PBA treatment for 24-hour decreased JNK expression in PC3 and LNCaP cells in 2D models. Both PBA and colchicine increased p38 expression in PC3 spheroids. PBA’s effects on cell deformation were visualized in semi-thin sections, marking the first ultrastructural observation of PBA-induced morphological defects in cancer cells.

Conclusion

PBA exerts antimitotic effects by inhibiting proliferation and migration and triggers diverse metabolic responses across different cell lines. Furthermore, PBA’s low toxicity on RWPE-1 cells suggests its potential as a promising chemotherapeutic agent for future studies.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/acamc/10.2174/0118715206352302241227031015
2025-01-20
2025-09-02

  • From This Site

    /content/journals/acamc/10.2174/0118715206352302241227031015
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SiegelR.L. GiaquintoA.N. JemalA. Cancer statistics, 2024.CA Cancer J. Clin.2024741124910.3322/caac.2182038230766
     [Google Scholar]
  2. HarrisA.E. MetzlerV.M. RoyL.J. VarunD. WoodcockC.L. HaighD.B. EndeleyC. HaqueM. TossM.S. AlsaleemM. PerssonJ.L. GudasL.J. RakhaE. RobinsonB.D. KhaniF. MartinL.M. MoyerJ.E. BrownlieJ. MadhusudanS. AllegrucciC. JamesV.H. RutlandC.S. FrayR.G. NtekimA. Brotd.S. MonganN.P. JeyapalanJ.N. Exploring anti-androgen therapies in hormone dependent prostate cancer and new therapeutic routes for castration resistant prostate cancer.Front. Endocrinol.202213100610110.3389/fendo.2022.100610136263323
     [Google Scholar]
  3. FerraldeschiR. WeltiJ. LuoJ. AttardG. Bonod.J.S. Targeting the androgen receptor pathway in castration-resistant prostate cancer: Progresses and prospects.Oncogene201534141745175710.1038/onc.2014.11524837363
     [Google Scholar]
  4. ShafiA.A. YenA.E. WeigelN.L. Androgen receptors in hormone-dependent and castration-resistant prostate cancer.Pharmacol. Ther.2013140322323810.1016/j.pharmthera.2013.07.00323859952
     [Google Scholar]
  5. PalmbergC. KoivistoP. VisakorpiT. TammelaT.L.J. PSA decline is an independent prognostic marker in hormonally treated prostate cancer.Eur. Urol.199936319119610.1159/00006799610450001
     [Google Scholar]
  6. SaraonP. DrabovichA.P. JarviK.A. DiamandisE.P. Mechanisms of androgen-independent prostate cancer.EJIFCC2014251425427683456
     [Google Scholar]
  7. ChandrasekarT. YangJ.C. GaoA.C. EvansC.P. Mechanisms of resistance in castration-resistant prostate cancer (CRPC).Transl. Androl. Urol.20154336538010.3978/J.ISSN.2223‑4683.2015.05.0226814148
     [Google Scholar]
  8. TürkC. NeisiusA. PetrikA. EAU guidelines on interventional treatment for urolithiasis.Europ. Urol.2016693475482
     [Google Scholar]
  9. RamjanA HossainM RunaJF MdH MahmodulI. Evaluation of thrombolytic potential of three medicinal plants available in Bangladesh, as a potent source of thrombolytic compounds.Avicenna. J. Phytomed.20144643043625386407
     [Google Scholar]
  10. GeorgeK. ThomasN.S. MalathiR. Modulatory effect of selected dietary phytochemicals on delayed rectifier K+ current in human prostate cancer cells.J. Membr. Biol.20192522-319520610.1007/s00232‑019‑00070‑931165179
     [Google Scholar]
  11. PageL.C. KoumakpayiI.H. FahmyA.M. MassonM.A-M. SaadF. Expression and localisation of Akt-1, Akt-2 and Akt-3 correlate with clinical outcome of prostate cancer patients.Br. J. Cancer200694121906191210.1038/sj.bjc.660318416721361
     [Google Scholar]
  12. BerishR.B. AliA.N. TelmerP.G. RonaldJ.A. LeongH.S. Translational models of prostate cancer bone metastasis.Nat. Rev. Urol.20181540342110.1038/s41585‑018‑0020‑2
     [Google Scholar]
  13. WangY. XiaY. LuZ. Metabolic features of cancer cells.Cancer Commun.20183811610.1186/s40880‑018‑0335‑730376896
     [Google Scholar]
  14. MurphyB.T. MacKinnonS.L. YanX. HammondG.B. VaisbergA.J. NetoC.C. Identification of triterpene hydroxycinnamates with in vitro antitumor activity from whole cranberry fruit (Vaccinium macrocarpon).J. Agric. Food Chem.200351123541354510.1021/jf034114g12769521
     [Google Scholar]
  15. LiX. WangX. ZhangJ. HanagataN. WangX. WengQ. ItoA. BandoY. GolbergD. Hollow boron nitride nanospheres as boron reservoir for prostate cancer treatment.Nat. Commun.2017811393610.1038/ncomms1393628059072
     [Google Scholar]
  16. MarasovicM. IvankovicS. StojkovicR. DjermicD. GalicB. MilosM. In vitro and in vivo antitumour effects of phenylboronic acid against mouse mammary adenocarcinoma 4T1 and squamous carcinoma SCCVII cells.J. Enzyme Inhib. Med. Chem.20173211299130410.1080/14756366.2017.138482329072095
     [Google Scholar]
  17. WilliamsG.M.T. ChapinR.E. KingP.E. MoserG.J. GoldsworthyT.L. MorrisonJ.P. MaronpotR.R. Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice.Toxicol. Pathol.2004321737810.1080/0192623049026089914713551
     [Google Scholar]
  18. BarrancoW.T. HudakP.F. EckhertC.D. Evaluation of ecological and in vitro effects of boron on prostate cancer risk (United States).Canc. Caus. Cont.2007181717710.1007/s10552‑006‑0077‑817186423
     [Google Scholar]
  19. McAuleyE.M. BradkeT.A. PlopperG.E. Phenylboronic acid is a more potent inhibitor than boric acid of key signaling networks involved in cancer cell migration.Cell Adhes. Migr.20115538238610.4161/cam.5.5.1816221975546
     [Google Scholar]
  20. PsurskiM. SłowikŁ.A. WoźniakA.A. WietrzykJ. SporzyńskiA. Discovering simple phenylboronic acid and benzoxaborole derivatives for experimental oncology – phase cycle-specific inducers of apoptosis in A2780 ovarian cancer cells.Invest. New Drugs2019371354610.1007/s10637‑018‑0611‑z29779163
     [Google Scholar]
  21. KaurR. KaurG. GillR.K. SoniR. BariwalJ. Recent developments in tubulin polymerization inhibitors: An overview.Eur. J. Med. Chem.2014878912410.1016/j.ejmech.2014.09.05125240869
     [Google Scholar]
  22. QinM. PengS. LiuN. HuM. HeY. LiG. ChenH. HeY. ChenA. WangX. LiuM. ChenY. YiZ. LG308, a novel synthetic compound with antimicrotubule activity in prostate cancer cells, exerts effective antitumor activity.J. Pharmacol. Exp. Ther.2015355347348310.1124/jpet.115.22591226377911
     [Google Scholar]
  23. MukhtarE. AdhamiV.M. SechiM. MukhtarH. Dietary flavonoid fisetin binds to β-tubulin and disrupts microtubule dynamics in prostate cancer cells.Cancer Lett.2015367217318310.1016/j.canlet.2015.07.03026235140
     [Google Scholar]
  24. BatesD. EastmanA. Microtubule destabilising agents: Far more than just antimitotic anticancer drugs.Br. J. Clin. Pharmacol.201783225526810.1111/bcp.1312627620987
     [Google Scholar]
  25. StoneA.A. ChambersT.C. Microtubule inhibitors elicit differential effects on MAP kinase (JNK, ERK, and p38) signaling pathways in human KB-3 carcinoma cells.Exp. Cell Res.2000254111011910.1006/excr.1999.473110623471
     [Google Scholar]
  26. ShtilA.A. MandlekarS. YuR. Differential regulation of mitogen-activated protein kinases by microtubule-binding agents in human breast cancer cells.Oncogene199918237738410.1038/sj.onc.1202305
     [Google Scholar]
  27. BarrancoW.T. EckhertC.D. Cellular changes in boric acid-treated DU-145 prostate cancer cells.Br. J. Cancer200694688489010.1038/sj.bjc.660300916495920
     [Google Scholar]
  28. OhJ. AnH.J. YeoH.J. ChoiS. OhJ. KimS. KimJ.M. ChoiJ. LeeS. Colchicine as a novel drug for the treatment of osteosarcoma through drug repositioning based on an FDA drug library.Front. Oncol.20221289395110.3389/fonc.2022.89395136059694
     [Google Scholar]
  29. KurekJ MyszkowskiK KozarynO.I Cytotoxic, analgesic and anti-inflammatory activity of colchicine and its C-10 sulfur containing derivatives.Sci. Rep.202111111210.1038/s41598‑021‑88260‑1
     [Google Scholar]
  30. BradkeT.M. HallC. CarperS.W. PlopperG.E. Phenylboronic acid selectively inhibits human prostate and breast cancer cell migration and decreases viability.Cell Adhes. Migr.20082315316010.4161/cam.2.3.648419262119
     [Google Scholar]
  31. RolfoA. GiuffridaD. GiuffridaM.C. TodrosT. CalogeroA.E. New perspectives for prostate cancer treatment: In vitro inhibition of LNCaP and PC3 cell proliferation by amnion-derived mesenchymal stromal cells conditioned media.Aging Male20141729410110.3109/13685538.2014.89689424597941
     [Google Scholar]
  32. GannonP.O. EthierG.J. HasslerM. DelvoyeN. AversaM. PoissonA.O. PéantB. FahmyA.M. SaadF. LapointeR. MassonM.A.M. Androgen-regulated expression of arginase 1, arginase 2 and interleukin-8 in human prostate cancer.PLoS One201058e1210710.1371/journal.pone.001210720711410
     [Google Scholar]
  33. ShenR. SumitomoM. DaiJ. HarrisA. KaminetzkyD. GaoM. BurnsteinK.L. NanusD.M. Androgen-induced growth inhibition of androgen receptor expressing androgen-independent prostate cancer cells is mediated by increased levels of neutral endopeptidase.Endocrinology200014151699170410.1210/endo.141.5.746310803579
     [Google Scholar]
  34. LaurenzanaA. BalliuM. CellaiC. RomanelliM.N. PaolettiF. Effectiveness of the histone deacetylase inhibitor (S)-2 against LNCaP and PC3 human prostate cancer cells.PLoS One201383e5826710.1371/journal.pone.005826723469273
     [Google Scholar]
  35. SintichS.M. SteinbergJ. KozlowskiJ.M. Cytotoxic sensitivity to tumor necrosis factor-in PC3 and LNCaP prostatic cancer cells is regulated by extracellular levels of SGP-2.Clusterin19993928793
     [Google Scholar]
  36. BelloD. WebberM.M. KleinmanH.K. WartingerD.D. RhimJ.S. Androgen responsive adult human prostatic epithelial cell lines immortalized by human papillomavirus 18.Carcinogenesis19971861215122310.1093/carcin/18.6.12159214605
     [Google Scholar]
  37. WebberM. BelloD. KleinmanH.K. HoffmanM.P. Acinar differentiation by non-malignant immortalized human prostatic epithelial cells and its loss by malignant cells.Carcinogenesis19971861225123110.1093/carcin/18.6.12259214606
     [Google Scholar]
  38. AchanzarW.E. AchanzarK.B. LewisJ.G. WebberM.M. WaalkesM.P. Cadmium induces c-myc, p53, and c-jun expression in normal human prostate epithelial cells as a prelude to apoptosis.Toxicol. Appl. Pharmacol.2000164329130010.1006/taap.1999.890710799339
     [Google Scholar]
  39. QuaderS.T.A. DeOcampoB.D. WilliamsD.E. KleinmanH.K. WebberM.M. Evaluation of the chemopreventive potential of retinoids using a novel in vitro human prostate carcinogenesis model.Mutat. Res. Genet. Toxicol. Environ. Mutagen.20014961-215316110.1016/S1383‑5718(01)00230‑311551491
     [Google Scholar]
  40. BulbulM. KarabulutS. KalenderM. KeskinI. Effects of gallic acid on endometrial cancer cells in two and three dimensional cell culture models.Asian Pac. J. Cancer Prev.20212261745175110.31557/APJCP.2021.22.6.174534181329
     [Google Scholar]
  41. MartinottiS. RanzatoE. Scratch wound healing assay.Methods Mol. Biol.2019210922522910.1007/7651_2019_25931414347
     [Google Scholar]
  42. BanerjeeA. BiswasR. LimR. PasolliH.A. RaghavanS. Scanning electron microscopy of murine skin ultrathin sections and cultured keratinocytes.STAR Protoc.20212310072910.1016/j.xpro.2021.10072934458866
     [Google Scholar]
  43. FinkelsteinY. AksS.E. HutsonJ.R. JuurlinkD.N. NguyenP. RazD.G. PollakU. KorenG. BenturY. Colchicine poisoning: The dark side of an ancient drug.Clin. Toxicol.201048540741410.3109/15563650.2010.49534820586571
     [Google Scholar]
  44. LiuL. ChenM. GaoY. TianL. ZhangW. WangZ. Mechanism of action and side effects of colchicine based on biomechanical properties of cells.J. Microsc.2023291322923610.1111/jmi.1321237358710
     [Google Scholar]
  45. CarrA.A. Colchicine toxicity.Arch. Intern. Med.19651151293310.1001/archinte.1965.0386013003100514219498
     [Google Scholar]
  46. EleftheriouG. BacisG. FiocchiR. SebastianoR. Colchicine-induced toxicity in a heart transplant patient with chronic renal failure.Clin. Toxicol.200846982783010.1080/1556365070177970318608282
     [Google Scholar]
  47. FisherM.F. RaoS.S. Three‐dimensional culture models to study drug resistance in breast cancer.Biotechnol. Bioeng.202011772262227810.1002/bit.2735632297971
     [Google Scholar]
  48. KaushikV. YakisichJ.S. WayL.F. AzadN. IyerA.K.V. Chemoresistance of cancer floating cells is independent of their ability to form 3D structures: Implications for anticancer drug screening.J. Cell. Physiol.201923444445445310.1002/jcp.2723930191978
     [Google Scholar]
  49. VeineDM YaoH StaffordDR FayKS LivantDL A D-amino acid containing peptide as a potent, noncovalent inhibitor of α5β1 integrin in human prostate cancer invasion and lung colonization.Clin Exp Metastasis.201431437939310.1007/s10585‑013‑9634‑1
     [Google Scholar]
  50. AbelS.D.A. DadhwalS. GambleA.B. BairdS.K. Honey reduces the metastatic characteristics of prostate cancer cell lines by promoting a loss of adhesion.PeerJ201867e511510.7717/peerj.511530002964
     [Google Scholar]
  51. SchattenH. Brief overview of prostate cancer statistics, grading, diagnosis and treatment strategies.Adv. Exp. Med. Biol.2018109511410.1007/978‑3‑319‑95693‑0_130229546
     [Google Scholar]
  52. DehghaniM KianpourS ZangenehA PourM.Z. CXCL12 modulates prostate cancer cell adhesion by altering the levels or activities of β1-containing integrins.Int. J. Cell Biol.2014201498175010.1155/2014/981750
     [Google Scholar]
  53. KennedyN.J. DavisR.J. Role of JNK in tumor development.Cell Cycle20032319820010.4161/cc.2.3.38812734425
     [Google Scholar]
  54. WestonC. DavisR.J. The JNK signal transduction pathway.Curr. Opin. Genet. Dev.2002121142110.1016/S0959‑437X(01)00258‑111790549
     [Google Scholar]
  55. EferlR. RicciR. KennerL. ZenzR. DavidJ.P. RathM. WagnerE.F. Liver tumor development. c-Jun antagonizes the proapoptotic activity of p53.Cell2003112218119210.1016/S0092‑8674(03)00042‑412553907
     [Google Scholar]
  56. XuR. HuJ. The role of JNK in prostate cancer progression and therapeutic strategies.Biomed. Pharmacother.202012110967910.1016/j.biopha.2019.10967931810118
     [Google Scholar]
  57. KolomeichukS.N. TerranoD.T. LyleC.S. SabapathyK. ChambersT.C. Distinct signaling pathways of microtubule inhibitors – vinblastine and Taxol induce JNK‐dependent cell death but through AP‐1‐dependent and AP‐1‐independent mechanisms, respectively.FEBS J.200827581889189910.1111/j.1742‑4658.2008.06349.x18341588
     [Google Scholar]
  58. KamathA. MehalW. JainD. Colchicine-associated ring mitosis in liver biopsy and their clinical implications.J. Clin. Gastroenterol.20084291060106210.1097/MCG.0b013e31803815b418391833
     [Google Scholar]
  59. KyriakisJ.M. AvruchJ. Mammalian MAPK signal transduction pathways activated by stress and inflammation: A 10-year update.Physiol. Rev.201292268973710.1152/physrev.00028.201122535895
     [Google Scholar]
  60. KyriakisJ.M. AvruchJ. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation.Physiol Rev.200192268973710.1152/physrev.2001.81.2.807
     [Google Scholar]
  61. KyriakisJ.M. AvruchJ. Protein kinase cascades activated by stress and inflammatory cytokines.BioEssays199618756757710.1002/bies.9501807088757935
     [Google Scholar]
  62. XiaZ. DickensM. RaingeaudJ. DavisR.J. GreenbergM.E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis.Science (1979).199527052401326133110.1126/science.270.5240.1326
     [Google Scholar]
  63. SugiuraR. SatohR. TakasakiT. ERK: A double-edged sword in cancer. ERK-dependent apoptosis as a potential therapeutic strategy for cancer.Cells20211010250910.3390/cells1010250934685488
     [Google Scholar]
  64. LimW. JeongM. BazerF.W. SongG. Coumestrol inhibits proliferation and migration of prostate cancer cells by regulating AKT, ERK1/2, and JNK MAPK cell signaling cascades.J. Cell. Physiol.2017232486287110.1002/jcp.2549427431052
     [Google Scholar]
  65. AllianaS.A. MenouL. ManiéS. AntomarchiS.H. MilletM.A. GiuriatoS. FerruaB. RossiB. Microtubule integrity regulates src-like and extracellular signal-regulated kinase activities in human pro-monocytic cells. Importance for interleukin-1 production.J. Biol. Chem.199827363394340010.1074/jbc.273.6.33949452460
     [Google Scholar]
  66. NairR.R. SchwarzLA. Microtubule-disrupting agents increase transgene expression in A549 cells through the activation of the Src and ERK kinase pathway.Mol. Ther.200375
     [Google Scholar]
  67. SamarakoonR. HigginsP.J. MEK/ERK pathway mediates cell-shape-dependent plasminogen activator inhibitor type 1 gene expression upon drug-induced disruption of the microfilament and microtubule networks.J. Cell Sci.2002115153093310310.1242/jcs.115.15.309312118065
     [Google Scholar]
/content/journals/acamc/10.2174/0118715206352302241227031015
Loading
Anticancer Properties of Phenylboronic Acid in Androgen-Dependent (LNCaP) and Androgen-Independent (PC3) Prostate Cancer Cells via MAP Kinases by 2D and 3D Culture Methods
Anti-Cancer Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Cancer Agents) 25, 899 (2025); https://doi.org/10.2174/0118715206352302241227031015
/content/journals/acamc/10.2174/0118715206352302241227031015
/content/journals/acamc/10.2174/0118715206352302241227031015
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): electron microscopy; ERK; JNK; LNCaP; p38; PC3; Phenylboronic acid; Prostate cancer

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