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Cell-Line–Specific Cytotoxic and Antiproliferative Effects of Citrinin in A549 and HCT-116 Cells

Year 2026, Volume: 5 Issue: 1, 8 - 17, 05.02.2026
https://doi.org/10.71133/anatphar.1799869

Abstract

Citrinin (CIT) is a mycotoxin commonly found in foods and has been linked to toxicity in various cell types. In our study, we examined how CIT affects human lung adenocarcinoma (A549), colorectal cancer (HCT116), and healthy fibroblast (L929, used as a control) cells. Our MTS assays revealed that CIT reduced cell viability in a manner dependent on both dose and exposure time. Interestingly, HCT116 cells were more sensitive to CIT than A549 cells, suggesting that its effects can vary between cancer types. We also performed wound healing experiments to assess cell migration and proliferation. CIT significantly slowed these processes in cancer cells, while fibroblasts were less affected. These results indicate that CIT can hinder cancer cell spread, though not without affecting normal cells. Previous studies have proposed several mechanisms for CIT’s toxicity. It appears to promote apoptosis by generating reactive oxygen species, disrupting mitochondrial membrane potential, activating caspases, and inducing endoplasmic reticulum stress. While these anticancer effects are promising, CIT’s high toxicity to normal cells and limited selectivity remain major hurdles for therapeutic use. Overall, our findings shed light on CIT’s cytotoxic and antimigratory actions, emphasizing the need for further research to identify doses that maximize its anticancer potential while minimizing harm to healthy cells.

Ethical Statement

Studies conducted on laboratory-cultured cell lines do not require ethical approval.

Supporting Institution

This study was supported by the TÜBİTAK 2209-A University Students Research Projects Support Program.

Project Number

This study was supported by the TÜBİTAK 2209-A University Students Research Projects Support Program.

References

  • [1] Yüce H, Ünüvar S. Mikotoksinlerin in vitro ve in vivo antikanser aktivitelerinin değerlendirilmesi. J Lit Pharm Sci. 2022;11(2):143–151.
  • [2] Bennett JW, Klich M. Mycotoxins. Clin Microbiol Rev. 2003;16(3):497–516.
  • [3] Shekhar R, Raghavendra VB, Rachitha P. A comprehensive review of mycotoxins, their toxicity, and innovative detoxification methods. Toxicol Rep. 2025;14:101952.
  • [4] Silva LJG, Pereira AMPT, Pena A, Lino CM. Citrinin in foods and supplements: A review of occurrence and analytical methodologies. Foods. 2020;10(1):14.
  • [5] Kamle M, Mahato DK, Gupta A, Pandhi S, et al. Citrinin mycotoxin contamination in food and feed: Impact on agriculture, human health, and detection and management strategies. Toxins (Basel). 2022;14(2):85.
  • [6] Vrabcheva T, Usleber E, Dietrich R, Märtlbauer E. Co-occurrence of ochratoxin A and citrinin in cereals from Bulgarian villages with a history of Balkan endemic nephropathy. J Agric Food Chem. 2000;48(6):2483–2488.
  • [7] Wu D, Yang C, Yang M, Wu Y, et al. Citrinin-induced hepatotoxicity in mice is regulated by the Ca²⁺/endoplasmic reticulum stress signaling pathway. Toxins (Basel). 2022;14(4):259.
  • [8] Bouslimi A, Bouaziz C, Ayed-Boussema I, Hassen W, Bacha H. Individual and combined effects of ochratoxin A and citrinin on viability and DNA fragmentation in cultured Vero cells and on chromosome aberrations in mice bone marrow cells. Toxicology. 2008;251(1–3):1–7.
  • [9] Yu FY, Liao YC, Chang CH, Liu BH. Citrinin induces apoptosis in HL-60 cells via activation of the mitochondrial pathway. Toxicol Lett. 2006;161(2):143–151.
  • [10] Skrzydlewski P, Twarużek M, Grajewski J. Cytotoxicity of mycotoxins and their combinations on different cell lines: A review. Toxins (Basel). 2022;14(4):244.
  • [11] Ojuri OT, Ezekiel CN, Sulyok M, Ezeokoli OT, et al. Assessing the mycotoxicological risk from consumption of complementary foods by infants and young children in Nigeria. Food Chem Toxicol. 2018;121:37–50.
  • [12] Adam MAA, Tabana YM, Musa KB, Sandai DA. Effects of different mycotoxins on humans, cell genome and their involvement in cancer. Oncol Rep. 2017;37:1321–1336.
  • [13] Reddy RV, Mayura K, Hayes AW, Berndt WO. Embryocidal, teratogenic and fetotoxic effects of citrinin in rats. Toxicology. 1982;25(2–3):151–160.
  • [14] Hanika C, Carlton WW, Tuite J. Citrinin mycotoxicosis in the rabbit. Food Chem Toxicol. 1983;21(4):487–493.
  • [15] Zargar S, Wani TA. Food toxicity of mycotoxin citrinin and molecular mechanisms of its potential toxicity effects through implicated targets predicted by computer-aided multidimensional data analysis. Life (Basel). 2023;13(4):880.
  • [16] Flajs D, Peraica M. Toxicological properties of citrinin. Arh Hig Rada Toksikol. 2009;60(4):457–464.
  • [17] Arai M, Hibino T. Tumorigenicity of citrinin in male F344 rats. Cancer Lett. 1983;17(3):281–287.
  • [18] International Agency for Research on Cancer (IARC). Citrinin. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 40. Lyon: IARC; 1986. p. 67–75.
  • [19] Abudayyak M, Karaman EF, Ozden S. Mechanisms underlying citrinin-induced toxicity via oxidative stress and apoptosis mediated by mitochondrial-dependent pathway in SH-SY5Y cells. Drug Chem Toxicol. 2023;46(5):944–954.
  • [20] Kumar R, Dwivedi PD, Dhawan A, Das M, Ansari KM. Citrinin-generated reactive oxygen species cause cell cycle arrest leading to apoptosis via the intrinsic mitochondrial pathway in mouse skin. Toxicol Sci. 2011;122(2):557–566.
  • [21] Chen CC, Chan WH. Inhibition of citrinin-induced apoptotic biochemical signaling in human hepatoma G2 cells by resveratrol. Int J Mol Sci. 2009;10:3338–3357.
  • [22] Yüce H, Özek DA, Ünüvar S. Evaluation of the cytotoxic activity of citrinin on human prostate cancer cell lines. Acta Physiol. 2025;241(S733):68.
  • [23] Yüce H, Sahin Y, Türkmen NB, Özek DA, Ünüvar S, Çiftçi O. Apoptotic, cytotoxic and antimigratory activities of phenolic compounds. J Evol Biochem Physiol. 2022;58(6):1819–1833.
  • [24] Ünüvar S, Yüce H, Türkmen NB, Şenkal S, Özek DA, Bulut E, Doğan A. Patulinin karaciğer ve akciğer kanseri hücre hatları üzerindeki in vitro antitümör aktivitesi. Ankara Univ Eczacılık Fak Derg. 2022;46(2):393–404.
  • [25] Salah A, Bouaziz C, Amara I, Abid-Essefi S, Bacha H. Eugenol protects against citrinin-induced cytotoxicity and oxidative damages in cultured human colorectal HCT116 cells. Environ Sci Pollut Res Int. 2019;26(30):31374–31383.
  • [26] Martí-Quijal FJ, Franco-Campos F, Barba FJ, Ruiz MJ. Citrinin-induced cellular damage: Insights from SH-SY5Y cell line studies. Foods. 2025;14(3):356.
  • [27] Aydin Y, Orta Yilmaz B, Yildizbayrak N, Korkut A, et al. Evaluation of citrinin-induced toxic effects on mouse Sertoli cells. Drug Chem Toxicol. 2021;44(6):559–565.
  • [28] Chan WH. Citrinin induces apoptosis via a mitochondria-dependent pathway and inhibition of survival signals in embryonic stem cells, and causes developmental injury in blastocysts. Biochem J. 2007;404(2):317–326.
  • [29] Stupin Polančec D, Homar S, Jakšić D, Kopjar N, et al. Citrinin provoke DNA damage and cell-cycle arrest related to Chk2 and FANCD2 checkpoint proteins in hepatocellular and adenocarcinoma cell lines. Toxins (Basel). 2024;16(7):321.
  • [30] Johannessen LN, Nilsen AM, Løvik M. Mycotoxin-induced depletion of intracellular glutathione and altered cytokine production in the human alveolar epithelial cell line A549. Toxicol Lett. 2007;168(2):103–112.
  • [31] Salah A, Bouaziz C, Prola A, Pires da Silva J, Bacha H, Abid-Essefi S, Lemaire C. Citrinin induces apoptosis in human HCT116 colon cancer cells through endoplasmic reticulum stress. J Toxicol Environ Health A. 2017;80(23–24):1230–1241.
There are 31 citations in total.

Details

Primary Language English
Subjects Genotoxicity and Cytotoxicity, Pharmaceutical Toxicology
Journal Section Research Article
Authors

Arda Oğuz Aygördü This is me 0009-0002-2408-2058

Arda Bükrek This is me 0009-0006-0293-6816

Seher Salci This is me 0009-0003-5010-4035

Buse Elif Kürçe This is me 0009-0006-0197-8686

Hande Yüce 0000-0003-2907-2019

Dilan Aşkın Özek 0000-0001-9075-4807

Songül Ünüvar 0000-0001-8454-490X

Project Number This study was supported by the TÜBİTAK 2209-A University Students Research Projects Support Program.
Submission Date October 13, 2025
Acceptance Date December 15, 2025
Publication Date February 5, 2026
Published in Issue Year 2026 Volume: 5 Issue: 1

Cite

EndNote Aygördü AO, Bükrek A, Salci S, Kürçe BE, Yüce H, Aşkın Özek D, Ünüvar S (February 1, 2026) Cell-Line–Specific Cytotoxic and Antiproliferative Effects of Citrinin in A549 and HCT-116 Cells. Anatolian Journal of Pharmaceutical Sciences 5 1 8–17.

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