Skip to content
2000
image of Rosmarinic Acid as a Potential Therapeutic Agent against Neuroblastoma: Anticancer Activity and Molecular Docking Insights

Abstract

Introduction

Rosmarinic acid (RA) is a phenolic acid known for its important biological activities. Although it has been shown to inhibit various cancer cell types, its effects on the suppression and induction of apoptosis in neuroblastoma cells remain unclear. In this study, the antiproliferation and apoptosis-inducing effects of various concentrations of rosmarinic acid on neuroblastoma cells (SH-SY5Y) were investigated. Additionally, molecular docking analysis was conducted to examine the interaction between rosmarinic acid and the antiapoptotic protein BCL2.

Methods

SH-SY5Y cells were treated with rosmarinic acid at concentrations of 50, 100, 150, and 200 µg/ml for 24 hours. The percentages of apoptotic and necrotic cells in cultures treated with the lowest and highest concentrations were assessed using the Annexin V/PI staining method. Furthermore, the interaction between rosmarinic acid and BCL2 protein was analyzed using molecular docking techniques.

Results

The viability of rosmarinic acid-treated SH-SY5Y cells decreased. In SH-SY5Y cells, the percentage of late apoptotic cells increased to 40%. Molecular docking results showed that the benzene ring of rosmarinic acid formed pi-alkyl interactions with PHE71 and van der Waals interactions with SER64, ALA72, SER75, and VAL115 of BCL2. The lowest binding energy was calculated as -7.2 kcal/mol.

Discussion

RA demonstrated a suppressive effect on SH-SY5Y cells by targeting the antiapoptotic protein BCL2, suggesting a potential mechanism of action through the induction of apoptosis.

Conclusion

RA inhibited neuroblastoma SH-SY5Y cell proliferation and induced apoptotic cell death. It inhibited the proliferation of neuroblastoma SH-SY5Y cells and promoted apoptotic cell death, potentially through interaction with the BCL2 protein.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/acamc/10.2174/0118715206406705250911103628
2025-09-24
2025-11-07

  • From This Site

    /content/journals/acamc/10.2174/0118715206406705250911103628
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Bray F. Laversanne M. Sung H. Ferlay J. Siegel R.L. Soerjomataram I. Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024 74 3 229 263 10.3322/caac.21834 38572751
    [Google Scholar]
  2. Ponzoni M. Bachetti T. Corrias M.V. Brignole C. Pastorino F. Calarco E. Bensa V. Giusto E. Ceccherini I. Perri P. Recent advances in the developmental origin of neuroblastoma: An overview. J. Exp. Clin. Cancer Res. 2022 41 1 92 10.1186/s13046‑022‑02281‑w 35277192
    [Google Scholar]
  3. Qiu B. Matthay K.K. Advancing therapy for neuroblastoma. Nat. Rev. Clin. Oncol. 2022 19 8 515 533 10.1038/s41571‑022‑00643‑z 35614230
    [Google Scholar]
  4. Park J.R. Eggert A. Caron H. Neuroblastoma: Biology, prognosis, and treatment. Hematol. Oncol. Clin. North Am. 2010 24 1 65 86 10.1016/j.hoc.2009.11.011 20113896
    [Google Scholar]
  5. Pinto N.R. Applebaum M.A. Volchenboum S.L. Matthay K.K. London W.B. Ambros P.F. Nakagawara A. Berthold F. Schleiermacher G. Park J.R. Valteau-Couanet D. Pearson A.D.J. Cohn S.L. Advances in risk classification and treatment strategies for neuroblastoma. J. Clin. Oncol. 2015 33 27 3008 3017 10.1200/JCO.2014.59.4648 26304901
    [Google Scholar]
  6. Reshi Z.A. Ahmad W. Lukatkin A.S. Javed S.B. From nature to lab: A review of secondary metabolite biosynthetic pathways, environmental influences, and in vitro approaches. Metabolites 2023 13 8 895 10.3390/metabo13080895 37623839
    [Google Scholar]
  7. Czerwińska K. Radziejewska I. Rosmarinic acid: A potential therapeutic agent in gastrointestinal cancer management—A review. Int. J. Mol. Sci. 2024 25 21 11704 10.3390/ijms252111704 39519255
    [Google Scholar]
  8. Abotaleb M. Liskova A. Kubatka P. Büsselberg D. Therapeutic potential of plant phenolic acids in the treatment of cancer. Biomolecules 2020 10 2 221 10.3390/biom10020221 32028623
    [Google Scholar]
  9. Obeng E. Apoptosis (programmed cell death) and its signals - A review. Braz. J. Biol. 2021 81 4 1133 1143 10.1590/1519‑6984.228437 33111928
    [Google Scholar]
  10. Green D.R. The death receptor pathway of apoptosis. Cold Spring Harb. Perspect. Biol. 2022 14 2 a041053 10.1101/cshperspect.a041053 35105716
    [Google Scholar]
  11. Brown G.C. Cell death by phagocytosis. Nat. Rev. Immunol. 2024 24 2 91 102 10.1038/s41577‑023‑00921‑6 37604896
    [Google Scholar]
  12. Nadeem M. Imran M. Aslam Gondal T. Imran A. Shahbaz M. Muhammad Amir R. Martins N. Therapeutic potential of rosmarinic acid: A comprehensive review. Appl. Sci. 2019 9 3139 10.3390/app9153139
    [Google Scholar]
  13. Adomako-Bonsu A.G. Chan S.L.F. Pratten M. Fry J.R. Antioxidant activity of rosmarinic acid and its principal metabolites in chemical and cellular systems: Importance of physico-chemical characteristics. Toxicol. In Vitro 2017 40 248 255 10.1016/j.tiv.2017.01.016 28122265
    [Google Scholar]
  14. Lu Y. Hong Y. Zhang T. Chen Y. Wei Z. Gao C. Rosmarinic acid exerts anti-inflammatory effect and relieves oxidative stress via Nrf2 activation in carbon tetrachloride-induced liver damage. Food Nutr. Res. 2022 66 66 10.29219/fnr.v66.8359 36590857
    [Google Scholar]
  15. Li G.S. Jiang W.L. Tian J.W. Qu G.W. Zhu H.B. Fu F.H. In vitro and in vivo antifibrotic effects of rosmarinic acid on experimental liver fibrosis. Phytomedicine 2010 17 3-4 282 288 10.1016/j.phymed.2009.05.002 19524418
    [Google Scholar]
  16. Ghaffari H. Venkataramana M. Jalali Ghassam B. Chandra Nayaka S. Nataraju A. Geetha N.P. Prakash H.S. Rosmarinic acid mediated neuroprotective effects against H2O2-induced neuronal cell damage in N2A cells. Life Sci. 2014 113 1-2 7 13 10.1016/j.lfs.2014.07.010 25058919
    [Google Scholar]
  17. Han Y.H. Kee J.Y. Hong S.H. Rosmarinic acid activates AMPK to inhibit metastasis of colorectal cancer. Front. Pharmacol. 2018 9 68 10.3389/fphar.2018.00068 29459827
    [Google Scholar]
  18. Messeha S.S. Zarmouh N.O. Asiri A. Soliman K.F.A. Rosmarinic acid-induced apoptosis and cell cycle arrest in triple-negative breast cancer cells. Eur. J. Pharmacol. 2020 885 173419 10.1016/j.ejphar.2020.173419 32750370
    [Google Scholar]
  19. Liao X.Z. Gao Y. Sun L.L. Liu J.H. Chen H.R. Yu L. Chen Z.Z. Chen W.H. Lin L.Z. Rosmarinic acid reverses non‐small cell lung cancer cisplatin resistance by activating the MAPK signaling pathway. Phytother. Res. 2020 34 5 1142 1153 10.1002/ptr.6584 31985119
    [Google Scholar]
  20. Zhou X. Wang W. Li Z. Chen L. Wen C. Ruan Q. Xu Z. Liu R. Xu J. Bai Y. Deng J. Rosmarinic acid decreases the malignancy of pancreatic cancer through inhibiting Gli1 signaling. Phytomedicine 2022 95 153861 10.1016/j.phymed.2021.153861 34864627
    [Google Scholar]
  21. Zhang Y. Hu M. Liu L. Cheng X.L. Cai J. Zhou J. Wang T. Anticancer effects of Rosmarinic acid in OVCAR-3 ovarian cancer cells are mediated via induction of apoptosis, suppression of cell migration and modulation of lncRNA MALAT-1 expression. J. Balkan Union Oncol. 2018 23 3 763 768 30003749
    [Google Scholar]
  22. Radziejewska I. Supruniuk K. Nazaruk J. Karna E. Popławska B. Bielawska A. Galicka A. Rosmarinic acid influences collagen, MMPs, TIMPs, glycosylation and MUC1 in CRL-1739 gastric cancer cell line. Biomed. Pharmacother. 2018 107 397 407 10.1016/j.biopha.2018.07.123 30099344
    [Google Scholar]
  23. De La Rosa L.A. Moreno-Escamilla J.O. Rodrigo-García J. Alvarez-Parrilla E. Phenolic compounds. In: Postharvest Physiology and Biochemistry of Fruits and Vegetables. Woodhead Publishing 2019 253 271 10.1016/B978‑0‑12‑813278‑4.00012‑9
    [Google Scholar]
  24. Lyubitelev A. Studitsky V. Inhibition of cancer development by natural plant polyphenols: Molecular mechanisms. Int. J. Mol. Sci. 2023 24 13 10663 10.3390/ijms241310663 37445850
    [Google Scholar]
  25. Yesil-Celiktas O. Sevimli C. Bedir E. Vardar-Sukan F. Inhibitory effects of rosemary extracts, carnosic acid and rosmarinic acid on the growth of various human cancer cell lines. Plant Foods Hum. Nutr. 2010 65 2 158 163 10.1007/s11130‑010‑0166‑4 20449663
    [Google Scholar]
  26. Letai A. Apoptosis and cancer. Annu. Rev. Cancer Biol. 2017 1 1 275 294 10.1146/annurev‑cancerbio‑050216‑121933
    [Google Scholar]
  27. Messeha S. Zarmouh N. Mendonca P. Alwagdani H. Cotton C. Soliman K. Effects of gossypol on apoptosis related gene expression in racially distinct triple negative breast cancer cells. Oncol. Rep. 2019 42 2 467 478 10.3892/or.2019.7179 31173249
    [Google Scholar]
  28. Liu Y. Xu X. Tang H. Pan Y. Hu B. Huang G. Rosmarinic acid inhibits cell proliferation, migration, and invasion and induces apoptosis in human glioma cells. Int. J. Mol. Med. 2021 47 5 67 10.3892/ijmm.2021.4900 33649774
    [Google Scholar]
  29. Jang Y.G. Hwang K.A. Choi K.C. Rosmarinic acid, a component of rosemary tea, induced the cell cycle arrest and apoptosis through modulation of HDAC2 expression in prostate cancer cell lines. Nutrients 2018 10 11 1784 10.3390/nu10111784 30453545
    [Google Scholar]
  30. Zhang X. Dowling J.P. Zhang J. RIPK1 can mediate apoptosis in addition to necroptosis during embryonic development. Cell Death Dis. 2019 10 3 245 10.1038/s41419‑019‑1490‑8 30867408
    [Google Scholar]
  31. Cai J. Hu D. Sakya J. Sun T. Wang D. Wang L. Mao X. Su Z. ABIN-1 is a key regulator in RIPK1-dependent apoptosis (RDA) and necroptosis, and ABIN-1 deficiency potentiates necroptosis-based cancer therapy in colorectal cancer. Cell Death Dis. 2021 12 2 140 10.1038/s41419‑021‑03427‑y 33542218
    [Google Scholar]
  32. Alaaeldin R. Abdel-Rahman I.M. Ali F.E.M. Bekhit A.A. Elhamadany E.Y. Zhao Q.L. Cui Z.G. Fathy M. Dual topoisomerase I/II inhibition-induced apoptosis and necro-apoptosis in cancer cells by a novel ciprofloxacin derivative via RIPK1/RIPK3/MLKL activation. Molecules 2022 27 22 7993 10.3390/molecules27227993 36432094
    [Google Scholar]
  33. Sathishkumar N. Sathiyamoorthy S. Ramya M. Yang D.U. Lee H.N. Yang D.C. Molecular docking studies of anti-apoptotic BCL-2, BCL-XL, and MCL-1 proteins with ginsenosides from Panax ginseng. J. Enzyme Inhib. Med. Chem. 2012 27 5 685 692 10.3109/14756366.2011.608663 21919598
    [Google Scholar]
  34. Li Y. Inam M. Hasan M.W. Chen K. Zhang Z. Zhu Y. Huang J. Wu Z. Chen W. Li M. Optimizing antitumor effect of triple-negative breast cancer via rosmarinic acid–β-cyclodextrin inclusion complex. Pharmaceutics 2024 16 11 1408 10.3390/pharmaceutics16111408 39598532
    [Google Scholar]
/content/journals/acamc/10.2174/0118715206406705250911103628
Loading
Rosmarinic Acid as a Potential Therapeutic Agent against Neuroblastoma: Anticancer Activity and Molecular Docking Insights
Bentham Science Publishers ; https://doi.org/10.2174/0118715206406705250911103628
/content/journals/acamc/10.2174/0118715206406705250911103628
/content/journals/acamc/10.2174/0118715206406705250911103628
Loading

Data & Media loading...


  • Article Type:     Research Article
Keywords: cell proliferation ; apoptosis ; anticancer activity ; neuroblastoma ; Rosmarinic acid ; molecular docking

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