Hande YÜCE, Neşe BAŞAK TÜRKMEN, Selinay ŞENKAL, Dilan AŞKIN ÖZEK, Ezgi BULUT, Ayşegül DOĞAN, Songül ÜNÜVAR

PATULİNİN KARACİĞER VE AKCİĞER KANSERİ HÜCRE HATLARI ÜZERİNDEKİ İN VİTRO ANTİTÜMÖR AKTİVİTESİ

Amaç: Patulin, başta Aspergillus ve Penicilium olmak üzere bazı küf mantarları tarafından üretilen bir mikotoksin olup, hayvanlarda ve insanlarda mikotoksikozdan sorumludur. Patulinin antitümör aktivitesi hakkında hala çok ayrıntılı veriler bulunmamakla birlikte bazı raporlar hücresel apoptozu ve toksisiteyi indüklediğini göstermektedir. Bizim bu çalışmadaki amacımız patulinin insan karaciğer ve akciğer kanseri hücreleri üzerindeki antiproliferatif, antimigrasyon etkilerini ve apoptotik yolaklardaki gen ifadeleri üzerine etkisini belirlemektir.

Anahtar Kelimeler:

A549, apoptoz, HEP3B, kanser, mikotoksin, patulin

IN VITRO ANTITUMOR ACTIVITY OF PATULIN ON LİVER AND LUNG CANCER CELL LINES

Objective: Patulin is a mycotoxin produced by some molds, mainly Aspergillus and Penicillium, and is responsible for mycotoxicosis in animals and humans. Although there are still no detailed data on the antitumor activity of patulin, some reports indicate that it induces cellular apoptosis and toxicity. Our aim in this study is to determine the antiproliferative and antimigration effects of patulin on human liver and lung cancer cells and its effect on gene expressions in apoptotic pathways.

Keywords:

A549, apoptosis, cancer, HEP3B, mycotoxin, patulin,

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Referans1. Ismaiel, A.A., Papenbrock, J. (2017). Effect of patulin from penicillium vulpinum on the activity of glutathione-S-transferase and selected antioxidative enzymes in Maize. International Journal of Environmental Research and Public Health, 14(7), 825. [CrossRef]
Referans2. Puel, O., Galtier, P., Oswald, I.P. (2010). Biosynthesis and toxicological effects of patulin. Toxins (Basel), 2(4), 613-631. [CrossRef]
Referans3. Liu, B.H., Yu, F.Y., Wu, T.S., Li, S.Y., Su, M.C., Wang, M.C., Shih, S.M. (2003). Evaluation of genotoxic risk and oxidative DNA damage in mammalian cells exposed to mycotoxins, patulin and citrinin. Toxicology and Applied Pharmacology, 191(3), 255-63. [CrossRef]
Referans4. IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. IARC; Lyon, France: 1986. Some Naturally Occurring and Synthetic Food Components, Furocoumarins and Ultraviolet Radiation; pp. 83-98.
Referans5. Abastabar, M., Akbari, A., Akhtari, J., Hedayati, M. T., Shokohi, T., Mehrad-Majd, H., Ghalehnoei, H., Ghasemi, S. (2017). In vitro antitumor activity of patulin on cervical and colorectal cancer cell lines. Current Medical Mycology, 3(1), 25-29.[CrossRef]
Referans6. Boussabbeh, M., Ben Salem, I., Prola, A., Guilbert, A., Bacha, H., Abid-Essefi, S., Lemaire, C. (2015). Patulin induces apoptosis through ROS-mediated endoplasmic reticulum stress pathway. Toxicological Sciences, 144(2), 328-337.[CrossRef]
Referans7. Pal, S., Singh, N., & Ansari, K. M. (2017). Toxicological effects of patulin mycotoxin on the mammalian system: an overview. Toxicology Research, 6(6), 764–771. [CrossRef]
Referans8. Liu, J., Liu, Q., Han, J., Feng, J., Guo, T., Li, Z., Min, F., Jin, R., Peng, X. (2021). N-Acetylcysteine inhibits patulin-induced apoptosis by affecting ROS-mediated oxidative damage pathway. Toxins, 13(9), 595. [CrossRef]
Referans9. Barltrop, J.A., Owen, T.C., Cory, A.H., Cory, J.G. (1991). 5-(3- carboxymethoxyphenyl)-2-(4,5-dimethylthiazolyl)-3- (4-sulfophenyl) tetrazolium, inner salt (MTS) and related analogs of 3-(4,5-dimethylthiazolyl)-2,5- diphenyltetrazolium bromide (MTT) reducing to purple water-soluble formazans as cell-viability indicators. Bioorganic & Medicinal Chemistry Letters, 1(11), 611-614. [CrossRef]
Referans10. Liang, C.C., Park, A., Guan, J.L. (2007). In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nature Protocols, 2(2), 329-333. [CrossRef]
Referans11. Demirci, S., Doğan, A., Türkmen, N. B., Telci, D., Rizvanov, A. A., Şahin, F. (2017). Schiff base-Poloxamer P85 combination demonstrates chemotherapeutic effect on prostate cancer cells in vitro. Biomedicine & Pharmacotherapy, 86, 492-501. [CrossRef]
Referans12. Andersen, B., Smedsgaard, J., Frisvad, J.C. (2004). Penicillium expansum: Consistent production of patulin, chaetoglobosins, and other secondary metabolites in culture and their natural occurrence in fruit products. Journal of Agricultural and Food Chemistry, 52(8), 2421-2428. [CrossRef]
Referans13. Kwon, O., Soung, N. K., Thimmegowda, N. R., Jeong, S. J., Jang, J. H., Moon, D. O., Chung, J. K., Lee, K. S., Kwon, Y. T., Erikson, R. L., Ahn, J. S., Kim, B. Y. (2012). Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation. Cellular Signalling, 24(4), 943-950. [CrossRef]
Referans14. Liu, B. H., Wu, T. S., Yu, F. Y., Wang, C. H. (2006). Mycotoxin patulin activates the p38 kinase and JNK signaling pathways in human embryonic kidney cells. Toxicological Sciences, 89(2), 423-430. [CrossRef]
Referans15. Guo, X., Dong, Y., Yin, S., Zhao, C., Huo, Y., Fan, L. (2013). Patulin induces pro-survival functions via autophagy inhibition and p62 accumulation. Cell Death Disease, 4(10), e822. [CrossRef]
Referans16. Ferrer, E., Juan-García, A., Font, G., Ruiz, M. J. (2009). Reactive oxygen species induced by beauvericin, patulin and zearalenone in CHO-K1 cells. Toxicology In Vitro, 23(8), 1504-1509.[CrossRef]
Referans17. Alves, I., Oliveira, N., Laires, A., Rodrigues, A., Rueff, J. (2000). Induction of micronuclei and chromosomal aberrations by the mycotoxin patulin in mammalian cells: role of ascorbic acid as a modulator of patulin clastogenicity. Mutagenesis, 15(3), 229-34. [CrossRef]
Referans18. Burghardt, R. C., Barhoumi, R., Lewis, E. H., Bailey, R. H., Pyle, K. A., Clement, B. A., Phillips, T. D. (1992). Patulin-induced cellular toxicity: a vital fluorescence study. Toxicology and Applied Pharmacology, 112(2), 235-244. [CrossRef]
Referans19. Turkmen, N. B., Yuce, H., Ozek, D. A., Aslan, S., Yasar, S., Unuvar, S. (2021). Dose dependent cytotoxic activity of patulin on neuroblastoma, colon and breast cancer cell line. Annals of Medical Research, 28(9), 1767-1770.[CrossRef]
Referans20. Boussabbeh, M., Ben Salem, I., Rjiba-Touati, K., Bouyahya, C., Neffati, F., Najjar, M. F., Bacha, H., Abid-Essefi, S. (2016). The potential effect of patulin on mice bearing melanoma cells: an anti-tumour or carcinogenic effect? Tumour Biology, 37(5), 6285-6295. [CrossaRef]
Referans21. Wu, T. S., Liao, Y. C., Yu, F. Y., Chang, C. H., Liu, B. H. (2008). Mechanism of patulin-induced apoptosis in human leukemia cells (HL-60). Toxicology Letters, 183(1-3), 105-111.[CrossRef]
Referans22. Luft, P., Oostingh, G. J., Gruijthuijsen, Y., Horejs-Hoeck, J., Lehmann, I., Duschl, A. (2008). Patulin influences the expression of Th1/Th2 cytokines by activated peripheral blood mononuclear cells and T cells through depletion of intracellular glutathione. Environmental Toxicology, 23(1), 84-95.[CrossRef]
Referans23. Jin, H., Yin, S., Song, X., Zhang, E., Fan, L., Hu, H. (2016). p53 activation contributes to patulin-induced nephrotoxicity via modulation of reactive oxygen species generation. Scientific Reports, 6, 24455. [CrossRef]
Referans24. Zhou, S. M., Jiang, L. P., Geng, C. Y., Cao, J., & Zhong, L. F. (2010). Patulin-induced oxidative DNA damage and p53 modulation in HepG2 cells. Toxicon, 55(2-3), 390-395. [CrossRef]
Referans25. Saxena, N., Ansari, K. M., Kumar, R., Dhawan, A., Dwivedi, P. D., Das, M. (2009). Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p(53) and p(21/WAF1) proteins in skin of mice. Toxicology and Applied Pharmacology, 234(2), 192-201. [CrossRef]