Research Article
BibTex RIS Cite

Unveiling the Dual Role of Gastrodin: Cytotoxic and Antimetastatic Effects in Triple Negative Breast Cancer Cells and Safety in Mesenchymal Stem Cells

Year 2025, Volume: 4 Issue: 2, 89 - 98, 13.12.2025
https://doi.org/10.5281/zenodo.17786613
https://izlik.org/JA84TT83LP

Abstract

Triple-negative breast cancer (TNBC) represents an aggressive and therapeutically challenging subtype of breast carcinoma, characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. Given its propensity for metastasis and limited treatment options, novel therapeutic candidates are urgently needed. Gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated diverse pharmacological properties, including antioxidant, anti-inflammatory, and anticancer activities. This study aimed to investigate the antiproliferative and antimigratory effects of gastrodin on the MDA-MB-231 TNBC cell line and evaluate its cytotoxicity on non-malignant adipose-derived mesenchymal stem cells (ADMSCs) to assess selectivity. Cell viability was determined using the MTT assay across a concentration range of 5–1000 µM, and wound healing assays were employed to assess migratory behavior. Results indicated a dose-dependent reduction in MDA-MB-231 cell viability, with an IC₅₀ of 587.6 µM, while ADMSCs exhibited minimal cytotoxicity at 100 µM, suggesting a favorable safety profile. Furthermore, treatment with 100 µM gastrodin significantly inhibited cell migration compared with untreated controls. These findings underscore the potential of gastrodin as a candidate for TNBC therapy, particularly given its selective cytotoxicity toward malignant cells and its ability to suppress migration, a key step in metastasis. Collectively, this study contributes to the growing evidence supporting natural compounds as promising alternatives for combating aggressive breast cancer subtypes.

Ethical Statement

Since the study was conducted with commercially purchased cell culture lines, it is not subject to ethical approval.

References

  • 1. Sadri F, fatemeh Hosseini S, Rezaei Z, Fereidouni M. Hippo-YAP/TAZ signaling in breast cancer: reciprocal regulation of microRNAs and implications in precision medicine. Genes & Diseases. 2024;11(2):760–71.
  • 2. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: a cancer journal for clinicians. 2023;73(1).
  • 3. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clinical cancer research. 2007;13(15):4429–34.
  • 4. Schmid P, Adams S, Rugo HS, Schneeweiss A, Barrios CH, Iwata H, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. New England journal of medicine. 2018;379(22):2108–21.
  • 5. Paul CD, Mistriotis P, Konstantopoulos K. Cancer cell motility: lessons from migration in confined spaces. Nature reviews cancer. 2017;17(2):131–40.
  • 6. Majidpoor J, Mortezaee K. Steps in metastasis: an updated review. Medical Oncology. 2021;38(1):3.
  • 7. Taguchi H, Yosioka I, Yamasaki K, KIM I. Studies on the constituents of Gastrodia elata Blume. Chemical and Pharmaceutical Bulletin. 1981;29(1):55–62.
  • 8. Li Y, Zhang Y, Zhang Z, Hu Y, Cui X, Xiong Y. Quality evaluation of gastrodia elata tubers based on HPLC fingerprint analyses and quantitative analysis of multi-components by single marker. Molecules. 2019;24(8):1521.
  • 9. Dai Y, Ban W, Yang Z. Gastrodin, a promising natural small molecule for the treatment of central nervous system disorders, and its recent progress in synthesis, pharmacology and pharmacokinetics. International journal of molecular sciences. 2024;25(17):9540.
  • 10. El Menyiy N, Elouafy Y, Moubachir R, Abdnim R, Benali T, Taha D, et al. Chemistry, biological activities, and pharmacological properties of gastrodin: Mechanism insights. Chemistry & Biodiversity. 2024;21(6):e202400402.
  • 11. Liang W-Z, Jan C-R, Hsu S-S. Cytotoxic effects of gastrodin extracted from the rhizome of Gastrodia elata Blume in glioblastoma cells, but not in normal astrocytes, via the induction of oxidative stress-associated apoptosis that involved cell cycle arrest and p53 activation. Food and Chemical Toxicology. 2017;107:280–92.
  • 12. Shu G, Yang T, Wang C, Su H, Xiang M. Gastrodin stimulates anticancer immune response and represses transplanted H22 hepatic ascitic tumor cell growth: Involvement of NF-κB signaling activation in CD4+ T cells. Toxicology and Applied Pharmacology. 2013;269(3):270–9.
  • 13. Liu Z, Wang S, Zhang J, Wang Y, Wang Y, Zhang L, et al. Gastrodin, a traditional Chinese medicine monomer compound, can be used as adjuvant to enhance the immunogenicity of melanoma vaccines. International Immunopharmacology. 2019;74:105699.
  • 14. Jiang W, Zhang L, Shan W, Wu Z, Wang J, Shen C. Gastrodin promotes osteogenic differentiation by stimulating the Wnt/β-catenin signaling pathway. Molecular and Cellular Probes. 2025:102035.
  • 15. Sharma V, Sharma P, Singh TG. Wnt signalling pathways as mediators of neuroprotective mechanisms: therapeutic implications in stroke. Molecular Biology Reports. 2024;51(1):247.
  • 16. Wu X, Liu Z, Yu XY, Xu S, Luo J. Autophagy and cardiac diseases: Therapeutic potential of natural products. Medicinal Research Reviews. 2021;41(1):314–41.
  • 17. Selfa Aspiroz L, Mennecozzi M, Batlle L, Corneo B, Healy L, Kotter M, et al. Promoting the adoption of best practices and standards to enhance quality and reproducibility of stem cell research. Stem Cell Reports. 2025;20(7).
  • 18. Sobiesiak M, Fatyga N, Brzozowski A, Sikora A, Kupcewicz B, Maj M. Chromanone derivatives: Evaluating selective anticancer activity across human cell lines. Eur J Med Chem. 2025;295:117771.
  • 19. Sung S-E, Seo M-S, Kim Y-I, Kang K-K, Choi J-H, Lee S, et al. Human epidural AD–MSC exosomes improve function recovery after spinal cord injury in rats. Biomedicines. 2022;10(3):678.
  • 20. Bulbul MV, Mermer A, Kolbasi B, Kocabas F, Kalender SM, Kirectepe Aydin KA, et al. mTOR Pathway Inhibition, Anticancer Activity and In Silico Calculations of Novel Hydrazone Derivatives in Two-and Three-Dimensional Cultured Type 1 Endometrial Cancer Cells. Pharmaceuticals. 2024;17(12):1562.
  • 21. Bulbul MV, Karabulut S, Kalender M, Keskin I. Effects of gallic acid on endometrial cancer cells in two- and three-dimensional cell culture models. Asian Pacific Journal of Cancer Prevention: APJCP. 2021;22(6):1745.
  • 22. Xie Z, Zhou H, Ou T, Pei W, Fan X. The Function and Effectiveness of MSCs in Preclinical Models of Diseases. Stem Cell Transplantation: IntechOpen; 2024.
  • 23. Zuo H-J, Wang P-X, Ren X-Q, Shi H-L, Shi J-S, Guo T, et al. Gastrodin regulates PI3K/AKT-Sirt3 signaling pathway and proinflammatory mediators in activated microglia. Molecular Neurobiology. 2024;61(5):2728–44.
  • 24. Li S, Yang Q, Zhou Z, Yang X, Liu Y, Hao K, et al. Gastrodin protects retinal ganglion cells from ischemic injury by activating phosphatidylinositol 3-kinase/protein kinase B/nuclear factor erythroid 2-related factor 2 (PI3K/AKT/Nrf2) signaling pathway. Bioengineered. 2022;13(5):12625–36.
  • 25. Wang J, Wu M. The up-regulation of miR-21 by gastrodin to promote the angiogenesis ability of human umbilical vein endothelial cells by activating the signaling pathway of PI3K/Akt. Bioengineered. 2021;12(1):5402–10. 26. Shih P-C, Tzeng I-S, Chen Y-C, Chen M-L. Gastrodin mitigates ketamine-induced inhibition of F-actin remodeling and cell migration by regulating the rho signaling pathway. Biomedicines. 2025;13(3):649.
  • 27. Liu Y-M, Wu A-D, Chen Y, Ma T-F, Dong B-Z, She Z-G, et al. Gastrodin inhibits prostate cancer proliferation by targeting canonical Wnt/β-catenin signaling pathway. Medical Oncology. 2023;41(1):32.
  • 28. Chavda VP, Nalla LV, Balar P, Bezbaruah R, Apostolopoulos V, Singla RK, et al. Advanced phytochemical-based nanocarrier systems for the treatment of breast cancer. Cancers. 2023;15(4):1023.
There are 27 citations in total.

Details

Primary Language English
Subjects Biochemistry and Cell Biology (Other)
Journal Section Research Article
Authors

Suat Utku Keskin 0009-0004-6188-3342

Alper Sezgin 0009-0007-6393-2015

Semiha Mervenur Kalender 0000-0002-0885-3417

Muhammet Volkan Bülbül 0000-0003-1526-2065

Submission Date August 29, 2025
Acceptance Date September 3, 2025
Early Pub Date December 11, 2025
Publication Date December 13, 2025
DOI https://doi.org/10.5281/zenodo.17786613
IZ https://izlik.org/JA84TT83LP
Published in Issue Year 2025 Volume: 4 Issue: 2

Cite

APA Keskin, S. U., Sezgin, A., Kalender, S. M., & Bülbül, M. V. (2025). Unveiling the Dual Role of Gastrodin: Cytotoxic and Antimetastatic Effects in Triple Negative Breast Cancer Cells and Safety in Mesenchymal Stem Cells. Eurasian Journal of Molecular and Biochemical Sciences, 4(2), 89-98. https://doi.org/10.5281/zenodo.17786613