• Register
  • Login

Iranian Journal of Pharmaceutical Sciences

  • Home
  • Journal Info
    • About the Journal
    • Aims and Scope
    • Editorial Team
    • Indexing & Abstracting
    • Privacy Statement
    • Contact us
  • Issues
    • Current
    • Archives
  • New Submissions
  • Author Guidelines
  • Policies & Process
    • Peer Review
    • Publication Ethics
    • Open Access Policy
    • Plagiarism
    • Retraction Policies
    • Archiving
  • Ethical Considration
Advanced Search
  1. Home
  2. Archives
  3. Vol. 21 No. 1 (2025): IJPS_Volume 21_Issue 1 (2025)
  4. Research/Original Articles

Vol. 21 No. 1 (2025)

Bahman 2025

Evaluation of Genistein’s Cytotoxic and Apoptotic Effects on Human Foreskin Fibroblasts: A Molecular and Biochemical Analysis Effects of Genistein on Fibroblast cells

  • Mohammadreza Pourmohammad
  • Jina Khayatzadeh
  • Somaye Talaei
  • Farahnaz Molavi

Iranian Journal of Pharmaceutical Sciences, Vol. 21 No. 1 (2025), 21 Bahman 2025 , Page 259-270
https://doi.org/10.22037/ijps.v21i1.47498 Published: 2025-07-09

  • View Article
  • Download
  • Cite
  • References
  • Statastics
  • Share

Abstract

Genistein, a naturally occurring isoflavone in soybeans, has gained attention for its phytoestrogenic and antioxidant properties. Its role in endocrine modulation, oxidative stress regulation, and apoptosis suggests therapeutic potential in cancer and metabolic disorders. Foreskin fibroblasts serve as a model for studying genistein’s effects on cell proliferation, oxidative stress, and cytotoxicity. This study examines genistein’s influence on gene expression related to cell growth and stress responses, offering insights into its therapeutic or adverse effects. Human foreskin samples from seven donors (6–12 years old) were used. Fibroblasts were isolated via collagenase and trypsin digestion and cultured in DMEM with 10% FBS. Cells were treated with genistein (20–100 µM), and viability was assessed using MTT assays. Antioxidant enzyme activities (SOD, GPx, CAT) were quantified spectrophotometrically. Gene expression of Bax, Bcl-2, IGF-1, and Casp3 was analyzed via real-time PCR. Data were evaluated using t-tests and ANOVA, with p<0.05 considered significant. Genistein induced dose- and time-dependent cytotoxicity, significantly reducing cell survival above 40 µM. IC50 values decreased over time, confirming enhanced cytotoxicity. Enzyme activity assays showed reduced CAT, SOD, and GPx levels. Gene analysis revealed upregulation of pro-apoptotic markers (BAX, Casp3) and downregulation of anti-apoptotic genes (Bcl-2, IGF-1), with a BAX/Bcl-2 ratio exceeding one, indicating apoptosis. These findings highlight genistein’s potential as a therapeutic agent via oxidative stress modulation and apoptosis induction. This study confirms genistein’s cytotoxic effects on fibroblast cells through oxidative stress and apoptosis. Further research is needed to clarify its molecular mechanisms and optimize therapeutic applications.

Keywords:
  • Genistein
  • Cytotoxicity
  • Oxidative stress
  • Apoptosis
  • IJPS_Volume21_Issue1_Pages259-270

How to Cite

Pourmohammad, M., Khayatzadeh , J., Talaei, S., & Molavi, F. (2025). Evaluation of Genistein’s Cytotoxic and Apoptotic Effects on Human Foreskin Fibroblasts: A Molecular and Biochemical Analysis: Effects of Genistein on Fibroblast cells. Iranian Journal of Pharmaceutical Sciences, 21(1), 259–270. https://doi.org/10.22037/ijps.v21i1.47498
  • ACM
  • ACS
  • APA
  • ABNT
  • Chicago
  • Harvard
  • IEEE
  • MLA
  • Turabian
  • Vancouver
  • Endnote/Zotero/Mendeley (RIS)
  • BibTeX

References

Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA, Ahmad B, Atif M, Mubarak MS, Sytar O, Zhilina OM, Garsiya ER, Smeriglio A, Trombetta D, Pons DG, Martorell M, Cardoso SM, Razis AFA, Sunusi U, Kamal RM, Rotariu LS, Butnariu M, Docea AO, Calina D. Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits. Oxid Med Cell Longev. 2021 Jul 19;2021:3268136. doi: 10.1155/2021/3268136. PMID: 34336089; PMCID: PMC8315847.

Yu L, Rios E, Castro L, Liu J, Yan Y, Dixon D. Genistein: Dual Role in Women's Health. Nutrients. 2021 Aug 30;13(9):3048. doi: 10.3390/nu13093048. PMID: 34578926; PMCID: PMC8472782.

Nestor MS, Bhupalam V, Awad N, Hetzel JD. The Therapeutic Role of Genistein in Perimenopausal and Postmenopausal Women. J Clin Aesthet Dermatol. 2024 Oct;17(10):45-53. PMID: 39445324; PMCID: PMC11495164.

Tuli HS, Tuorkey MJ, Thakral F, Sak K, Kumar M, Sharma AK, Sharma U, Jain A, Aggarwal V, Bishayee A. Molecular Mechanisms of Action of Genistein in Cancer: Recent Advances. Front Pharmacol. 2019 Dec 6;10:1336. doi: 10.3389/fphar.2019.01336. PMID: 31866857; PMCID: PMC6910185.

Shete V, Mahajan NM, Shivhare R, Akkewar A, Gupta A, Gurav S. Genistein: A promising phytoconstituent with reference to its bioactivities. Phytother Res. 2024 Aug;38(8):3935-3953. doi: 10.1002/ptr.8256. Epub 2024 Jun 3. PMID: 38831683.

Kim IS. Current Perspectives on the Beneficial Effects of Soybean Isoflavones and Their Metabolites for Humans. Antioxidants (Basel). 2021 Jun 30;10(7):1064. doi: 10.3390/antiox10071064. PMID: 34209224; PMCID: PMC8301030.

Gómez-Zorita S, González-Arceo M, Fernández-Quintela A, Eseberri I, Trepiana J, Portillo MP. Scientific Evidence Supporting the Beneficial Effects of Isoflavones on Human Health. Nutrients. 2020 Dec 17;12(12):3853. doi: 10.3390/nu12123853. PMID: 33348600; PMCID: PMC7766685.

Patisaul HB, Jefferson W. The pros and cons of phytoestrogens. Front Neuroendocrinol. 2010 Oct;31(4):400-19. doi: 10.1016/j.yfrne.2010.03.003. Epub 2010 Mar 27. PMID: 20347861; PMCID: PMC3074428.

Kallifatidis G, Hoy JJ, Lokeshwar BL. Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer. Semin Cancer Biol. 2016 Oct;40-41:160-169. doi: 10.1016/j.semcancer.2016.06.003. Epub 2016 Jun 28. PMID: 27370570; PMCID: PMC5067195.

Faienza MF, Giardinelli S, Annicchiarico A, Chiarito M, Barile B, Corbo F, Brunetti G. Nutraceuticals and Functional Foods: A Comprehensive Review of Their Role in Bone Health. Int J Mol Sci. 2024 May 28;25(11):5873. doi: 10.3390/ijms25115873. PMID: 38892062; PMCID: PMC11172758.

Goh YX, Jalil J, Lam KW, Husain K, Premakumar CM. Genistein: A Review on its Anti-Inflammatory Properties. Front Pharmacol. 2022 Jan 24;13:820969. doi: 10.3389/fphar.2022.820969. PMID: 35140617; PMCID: PMC8818956.

Xin Y, Xu P, Wang X, Chen Y, Zhang Z, Zhang Y. Human foreskin-derived dermal stem/progenitor cell-conditioned medium combined with hyaluronic acid promotes extracellular matrix regeneration in diabetic wounds. Stem Cell Res Ther. 2021 Jan 9;12(1):49. doi: 10.1186/s13287-020-02116-5. PMID: 33422138; PMCID: PMC7796620.

Cialdai F, Risaliti C, Monici M. Role of fibroblasts in wound healing and tissue remodeling on Earth and in space. Front Bioeng Biotechnol. 2022 Oct 4;10:958381. doi: 10.3389/fbioe.2022.958381. PMID: 36267456; PMCID: PMC9578548.

Rahnama M, Ghasemzadeh N, Ebrahimi Y, Golchin A. A comprehensive evaluation of dermal fibroblast therapy in clinical trials for treating skin disorders and cosmetic applications: a scoping review. Stem Cell Res Ther. 2024 Sep 20;15(1):318. doi: 10.1186/s13287-024-03892-0. PMID: 39304949; PMCID: PMC11416016.

Nadalutti CA, Wilson SH. Using Human Primary Foreskin Fibroblasts to Study Cellular Damage and Mitochondrial Dysfunction. Curr Protoc Toxicol. 2020 Dec;86(1):e99. doi: 10.1002/cptx.99. PMID: 33202115; PMCID: PMC7757388.

Tao L, Huang G, Song H, Chen Y, Chen L. Cancer associated fibroblasts: An essential role in the tumor microenvironment. Oncol Lett. 2017 Sep;14(3):2611-2620. doi: 10.3892/ol.2017.6497. Epub 2017 Jun 30. PMID: 28927027; PMCID: PMC5588104.

Seaman SA, Tannan SC, Cao Y, Peirce SM, Lin KY. Differential Effects of Processing Time and Duration of Collagenase Digestion on Human and Murine Fat Grafts. Plast Reconstr Surg. 2015 Aug;136(2):189e-199e. doi: 10.1097/PRS.0000000000001446. PMID: 26218393; PMCID: PMC4676560.

Mehrabani D, Hassanshahi MA, Tamadon A, Zare S, Keshavarz S, Rahmanifar F, Dianatpour M, Khodabandeh Z, Jahromi I, Tanideh N, Ramzi M, Aqababa H, Kuhi-Hoseinabadi O. Adipose tissue-derived mesenchymal stem cells repair germinal cells of seminiferous tubules of busulfan-induced azoospermic rats. J Hum Reprod Sci. 2015 Apr-Jun;8(2):103-10. doi: 10.4103/0974-1208.158618. PMID: 26157302; PMCID: PMC4477447.

Holder CL, Churchwell MI, Doerge DR. Quantification of soy isoflavones, genistein and daidzein, and conjugates in rat blood using LC/ES-MS. J Agric Food Chem. 1999 Sep;47(9):3764-70. doi: 10.1021/jf9902651. PMID: 10552719.

Ghasemi M, Turnbull T, Sebastian S, Kempson I. The MTT Assay: Utility, Limitations, Pitfalls, and Interpretation in Bulk and Single-Cell Analysis. Int J Mol Sci. 2021 Nov 26;22(23):12827. doi: 10.3390/ijms222312827. PMID: 34884632; PMCID: PMC8657538.

Kamerkar S, LeBleu VS, Sugimoto H, Yang S, Ruivo CF, Melo SA, Lee JJ, Kalluri R. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 2017 Jun 22;546(7659):498-503. doi: 10.1038/nature22341. Epub 2017 Jun 7. PMID: 28607485; PMCID: PMC5538883.

Torrejón D, Cárdenas J, Juárez D, Espinoza J, Proleón A, Agurto-Arteaga A, Lazo F, Leguía M, Urra FA, Sánchez EF, Chávez-Olortegui C, Vivas-Ruiz DE, Yarlequé A. Comparison of Four Methods of RNA Extraction and cDNA Synthesis from The Venom of Peruvian Snakes of the Genus Bothrops of Clinical Importance. Int J Mol Sci. 2023 Jul 6;24(13):11161. doi: 10.3390/ijms241311161. PMID: 37446341; PMCID: PMC10342303.

Papin JF, Vahrson W, Dittmer DP. SYBR green-based real-time quantitative PCR assay for detection of West Nile Virus circumvents false-negative results due to strain variability. J Clin Microbiol. 2004 Apr;42(4):1511-8. doi: 10.1128/JCM.42.4.1511-1518.2004. PMID: 15070997; PMCID: PMC387603.

Alorda-Clara M, Torrens-Mas M, Morla-Barcelo PM, Roca P, Sastre-Serra J, Pons DG, Oliver J. High Concentrations of Genistein Decrease Cell Viability Depending on Oxidative Stress and Inflammation in Colon Cancer Cell Lines. Int J Mol Sci. 2022 Jul 7;23(14):7526. doi: 10.3390/ijms23147526. PMID: 35886874; PMCID: PMC9323408.

Pawlicka MA, Zmorzyński S, Popek-Marciniec S, Filip AA. The Effects of Genistein at Different Concentrations on MCF-7 Breast Cancer Cells and BJ Dermal Fibroblasts. Int J Mol Sci. 2022 Oct 15;23(20):12360. doi: 10.3390/ijms232012360. PMID: 36293214; PMCID: PMC9604460.

Canivenc-Lavier MC, Bennetau-Pelissero C. Phytoestrogens and Health Effects. Nutrients. 2023 Jan 9;15(2):317. doi: 10.3390/nu15020317. PMID: 36678189; PMCID: PMC9864699.

Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA, Ahmad B, Atif M, Mubarak MS, Sytar O, Zhilina OM, Garsiya ER, Smeriglio A, Trombetta D, Pons DG, Martorell M, Cardoso SM, Razis AFA, Sunusi U, Kamal RM, Rotariu LS, Butnariu M, Docea AO, Calina D. Genistein: An Integrative Overview of Its Mode of Action, Pharmacological Properties, and Health Benefits. Oxid Med Cell Longev. 2021 Jul 19;2021:3268136. doi: 10.1155/2021/3268136. PMID: 34336089; PMCID: PMC8315847.

Varesi A, Chirumbolo S, Campagnoli LIM, Pierella E, Piccini GB, Carrara A, Ricevuti G, Scassellati C, Bonvicini C, Pascale A. The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence. Antioxidants (Basel). 2022 Jun 22;11(7):1224. doi: 10.3390/antiox11071224. PMID: 35883714; PMCID: PMC9311946.

Behl T, Rana T, Alotaibi GH, Shamsuzzaman M, Naqvi M, Sehgal A, Singh S, Sharma N, Almoshari Y, Abdellatif AAH, Iqbal MS, Bhatia S, Al-Harrasi A, Bungau S. Polyphenols inhibiting MAPK signalling pathway mediated oxidative stress and inflammation in depression. Biomed Pharmacother. 2022 Feb;146:112545. doi: 10.1016/j.biopha.2021.112545. Epub 2021 Dec 15. PMID: 34922112.

Tophkhane C, Yang S, Bales W, Archer L, Osunkoya A, Thor AD, Yang X. Bcl-2 overexpression sensitizes MCF-7 cells to genistein by multiple mechanisms. Int J Oncol. 2007 Oct;31(4):867-74. PMID: 17786319.

Qian S, Wei Z, Yang W, Huang J, Yang Y, Wang J. The role of BCL-2 family proteins in regulating apoptosis and cancer therapy. Front Oncol. 2022 Oct 12;12:985363. doi: 10.3389/fonc.2022.985363. PMID: 36313628; PMCID: PMC9597512.

Raisova M, Hossini AM, Eberle J, Riebeling C, Wieder T, Sturm I, Daniel PT, Orfanos CE, Geilen CC. The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. J Invest Dermatol. 2001 Aug;117(2):333-40. doi: 10.1046/j.0022-202x.2001.01409.x. PMID: 11511312.

Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014 Oct 5;740:364-78. doi: 10.1016/j.ejphar.2014.07.025. Epub 2014 Jul 21. PMID: 25058905; PMCID: PMC4146684.

Wani AK, Akhtar N, Mir TUG, Singh R, Jha PK, Mallik SK, Sinha S, Tripathi SK, Jain A, Jha A, Devkota HP, Prakash A. Targeting Apoptotic Pathway of Cancer Cells with Phytochemicals and Plant-Based Nanomaterials. Biomolecules. 2023 Jan 18;13(2):194. doi: 10.3390/biom13020194. PMID: 36830564; PMCID: PMC9953589.

Pawlicka MA, Zmorzyński S, Popek-Marciniec S, Filip AA. The Effects of Genistein at Different Concentrations on MCF-7 Breast Cancer Cells and BJ Dermal Fibroblasts. Int J Mol Sci. 2022 Oct 15;23(20):12360. doi: 10.3390/ijms232012360. PMID: 36293214; PMCID: PMC9604460.

Banerjee S, Li Y, Wang Z, Sarkar FH. Multi-targeted therapy of cancer by genistein. Cancer Lett. 2008 Oct 8;269(2):226-42. doi: 10.1016/j.canlet.2008.03.052. Epub 2008 May 19. PMID: 18492603; PMCID: PMC2575691.

Ghaznavi H, Afzalipour R, Khoei S, Sargazi S, Shirvalilou S, Sheervalilou R. New insights into targeted therapy of glioblastoma using smart nanoparticles. Cancer Cell Int. 2024 May 7; 24(1):160. doi: 10.1186/s12935-024-03331-3. PMID: 38715021; PMCID: PMC11077767.

  • Abstract Viewed: 275 times
  • IJPS_Volume21_Issue1_Pages259-270 Downloaded: 219 times

Download Statastics

  • Linkedin
  • Twitter
  • Facebook
  • Google Plus
  • Telegram

Developed By

Open Journal Systems

Information

  • For Readers
  • For Authors
  • For Librarians
  • Home
  • Archives
  • Submissions
  • About the Journal
  • Editorial Team
  • Contact

Creative Commons License
This journal (and its contents) is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Print ISSN: 1735-2444

Online ISSN: 2252-0457

Powered by OJSPlus