<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20241031//EN"
        "https://jats.nlm.nih.gov/publishing/1.4/JATS-journalpublishing1-4.dtd">
<article  article-type="research-article"        dtd-version="1.4">
            <front>

                <journal-meta>
                                                                <journal-id>j. fac. pharm. ankara</journal-id>
            <journal-title-group>
                                                                                    <journal-title>Journal of Faculty of Pharmacy of Ankara University</journal-title>
            </journal-title-group>
                            <issn pub-type="ppub">1015-3918</issn>
                                        <issn pub-type="epub">2564-6524</issn>
                                                                                            <publisher>
                    <publisher-name>Ankara University</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id pub-id-type="doi">10.33483/jfpau.1078080</article-id>
                                                                <article-categories>
                                            <subj-group  xml:lang="en">
                                                            <subject>Pharmacology and Pharmaceutical Sciences</subject>
                                                    </subj-group>
                                            <subj-group  xml:lang="tr">
                                                            <subject>Eczacılık ve İlaç Bilimleri</subject>
                                                    </subj-group>
                                    </article-categories>
                                                                                                                                                        <title-group>
                                                                                                                        <trans-title-group xml:lang="en">
                                    <trans-title>IN VITRO ANTITUMOR ACTIVITY OF PATULIN ON LİVER AND LUNG CANCER CELL LINES</trans-title>
                                </trans-title-group>
                                                                                                                                                                                                <article-title>PATULİNİN KARACİĞER VE AKCİĞER KANSERİ HÜCRE HATLARI ÜZERİNDEKİ İN VİTRO ANTİTÜMÖR AKTİVİTESİ</article-title>
                                                                                                    </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0003-2907-2019</contrib-id>
                                                                <name>
                                    <surname>Yüce</surname>
                                    <given-names>Hande</given-names>
                                </name>
                                                                    <aff>INONU UNIVERSITY, FACULTY OF PHARMACY</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0001-5566-8321</contrib-id>
                                                                <name>
                                    <surname>Başak Türkmen</surname>
                                    <given-names>Neşe</given-names>
                                </name>
                                                                    <aff>İNÖNÜ ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-6897-7307</contrib-id>
                                                                <name>
                                    <surname>Şenkal</surname>
                                    <given-names>Selinay</given-names>
                                </name>
                                                                    <aff>YEDITEPE UNIVERSITY</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0001-9075-4807</contrib-id>
                                                                <name>
                                    <surname>Aşkın Özek</surname>
                                    <given-names>Dilan</given-names>
                                </name>
                                                                    <aff>FIRAT UNIVERSITY</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0001-5842-6088</contrib-id>
                                                                <name>
                                    <surname>Bulut</surname>
                                    <given-names>Ezgi</given-names>
                                </name>
                                                                    <aff>YEDITEPE UNIVERSITY</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0003-4160-2270</contrib-id>
                                                                <name>
                                    <surname>Doğan</surname>
                                    <given-names>Ayşegül</given-names>
                                </name>
                                                                    <aff>YEDITEPE UNIVERSITY</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0001-8454-490X</contrib-id>
                                                                <name>
                                    <surname>Ünüvar</surname>
                                    <given-names>Songül</given-names>
                                </name>
                                                                    <aff>INONU UNIVERSITY</aff>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20220529">
                    <day>05</day>
                    <month>29</month>
                    <year>2022</year>
                </pub-date>
                                        <volume>46</volume>
                                        <issue>2</issue>
                                        <fpage>393</fpage>
                                        <lpage>404</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20220224">
                        <day>02</day>
                        <month>24</month>
                        <year>2022</year>
                    </date>
                                                    <date date-type="accepted" iso-8601-date="20220419">
                        <day>04</day>
                        <month>19</month>
                        <year>2022</year>
                    </date>
                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 1971, Journal of Faculty of Pharmacy of Ankara University</copyright-statement>
                    <copyright-year>1971</copyright-year>
                    <copyright-holder>Journal of Faculty of Pharmacy of Ankara University</copyright-holder>
                </permissions>
            
                                                                                                <trans-abstract xml:lang="en">
                            <p>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.Material and Method: HEP3B and A549 cell lines were used to determine the efficacy of patulin in the treatment of liver and lung cancers. Cell lines were exposed to increasing concentrations of patulin (1, 2.5, 5, 10, 25, 50, and 100 µM), followed by determination of cell viability, cell migration, and apoptosis by MTS assay, wound healing assay, and RT-PCR assays.Result and Discussion: Patulin caused a dose-dependent significant decrease in cell viability and cell migration in both cancer cell lines. It also promoted the induction of apoptosis in both cell lines. Our results showed that patulin can significantly reduce tumor growth in human liver and lung cancer cells in vitro.</p></trans-abstract>
                                                                                                                                    <abstract><p>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.Gereç ve Yöntem: Patulinin karaciğer ve akciğer kanserleri tedavisindeki etkinliğini belirlemek için HEP3B ve A549 hücre hatları kullanıldı. Hücre hatları, artan konsantrasyonlarda patuline (1, 2.5, 5, 10, 25, 50 ve 100 µM) maruz bırakıldı, ardından MTS testi, yara iyileşme testi ve RT-PCR deneyleri ile, hücre canlılığı, hücre göçü ve apoptoz belirlendi.Sonuç ve Tartışma: Patulin her iki kanser hücre hattında da doza bağlı olarak hücre canlılığında ve hücre göçünde önemli bir azalmaya neden oldu Ayrıca her iki hücre hattında da apoptozun indüksiyonunu teşvik etti. Sonuçlarımız patulinin insan karaciğer ve akciğer kanser hücrelerinde tümör büyümesini in vitro olarak önemli ölçüde azaltabileceğini gösterdi.</p></abstract>
                                                            
            
                                                                                        <kwd-group>
                                                    <kwd>A549</kwd>
                                                    <kwd>  apoptoz</kwd>
                                                    <kwd>  HEP3B</kwd>
                                                    <kwd>  kanser</kwd>
                                                    <kwd>  mikotoksin</kwd>
                                                    <kwd>  patulin</kwd>
                                            </kwd-group>
                            
                                                <kwd-group xml:lang="en">
                                                    <kwd>A549</kwd>
                                                    <kwd>  apoptosis</kwd>
                                                    <kwd>  cancer</kwd>
                                                    <kwd>  HEP3B</kwd>
                                                    <kwd>  mycotoxin</kwd>
                                                    <kwd>  patulin</kwd>
                                            </kwd-group>
                                                                                                                                    <funding-group specific-use="FundRef">
                    <award-group>
                                                    <funding-source>
                                <named-content content-type="funder_name">İNÖNÜ ÜNİVERSİTESİ BİLİMSEL ARAŞTIRMA PROJE BİRİMİ (İUBAP)</named-content>
                            </funding-source>
                                                                            <award-id>TSG-2020-2087</award-id>
                                            </award-group>
                </funding-group>
                                </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">Referans2.	Puel, O., Galtier, P., Oswald, I.P. (2010). Biosynthesis and toxicological effects of patulin. Toxins (Basel), 2(4), 613-631. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">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.</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">Referans7.	Pal, S., Singh, N., &amp; Ansari, K. M. (2017). Toxicological effects of patulin mycotoxin on the mammalian system: an overview. Toxicology Research, 6(6), 764–771. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">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 &amp; Medicinal Chemistry Letters, 1(11), 611-614. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">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 &amp; Pharmacotherapy, 86, 492-501. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref23">
                        <label>23</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                                    <ref id="ref24">
                        <label>24</label>
                        <mixed-citation publication-type="journal">Referans24.	Zhou, S. M., Jiang, L. P., Geng, C. Y., Cao, J., &amp; Zhong, L. F. (2010). Patulin-induced oxidative DNA damage and p53 modulation in HepG2 cells. Toxicon, 55(2-3), 390-395. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref25">
                        <label>25</label>
                        <mixed-citation publication-type="journal">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]</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
