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Erschienen in: Tumor Biology 5/2016

30.11.2015 | Original Article

The potential effect of patulin on mice bearing melanoma cells: an anti-tumour or carcinogenic effect?

verfasst von: Manel Boussabbeh, Intidhar Ben Salem, Karima Rjiba-Touati, Chedy Bouyahya, Fadwa Neffati, Mohamed Fadhel Najjar, Hassen Bacha, Salwa Abid-Essefi

Erschienen in: Tumor Biology | Ausgabe 5/2016

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Abstract

Mycotoxins are bioactive compounds that are noxious to human. Their effects on oncogenesis have been satisfactorily elucidated, and some of mycotoxins have been classified as carcinogenic to humans. Nevertheless, patulin (PAT) is considered by the International Agency of Research on Cancer as ‘not carcinogenic to humans’. The present study was designed to understand the effect of this mycotoxin on melanoma cells (B16F10) by measuring cell proliferation and assessing the anti-tumour effect in vivo in Balb/c mice. Our results revealed that intraperitoneally administration of PAT for 20 days significantly induces tumour regression in B16F10 cell-implanted mice. This effect was evidenced by the activation of apoptosis which is supported by the increase in p53 and Bax expressions, the downregulation of the protein levels of Bcl2, and the increase in caspase-3 activity. Moreover, systemic toxicity analysis demonstrated that there is no potential toxicity following PAT treatment unlike untreated melanoma mice which suffer from anaemia, inflammation and liver dysfunction. Remarkably, this is the first published report demonstrating the therapeutic efficacy of PAT in vivo models.
Literatur
1.
Zurück zum Zitat Zagrouba E, Barhoumi W. A prelimary approach for the automated recognition of malignant melanoma. Image Anal Stereol. 2004;23:121–35.CrossRef Zagrouba E, Barhoumi W. A prelimary approach for the automated recognition of malignant melanoma. Image Anal Stereol. 2004;23:121–35.CrossRef
2.
Zurück zum Zitat Gray-Schopfer V, Wellbrock C, Marais R. Review Article Melanoma biology and new targeted therapy. Nature. 2007;445:851–7.CrossRefPubMed Gray-Schopfer V, Wellbrock C, Marais R. Review Article Melanoma biology and new targeted therapy. Nature. 2007;445:851–7.CrossRefPubMed
4.
Zurück zum Zitat Hariz W, Chabéne H, Masmoudi A, Miziou TJ, Mseddi M, Turki H. Changement du profil épidémiologique du mélanome cutané en Tunisie au cours des deux dernières décennies. Annales de Dermatologie et de Vénéréologie Volume 139, n° 12S. doi:10.1016/j.annder.2012.10.494. Hariz W, Chabéne H, Masmoudi A, Miziou TJ, Mseddi M, Turki H. Changement du profil épidémiologique du mélanome cutané en Tunisie au cours des deux dernières décennies. Annales de Dermatologie et de Vénéréologie Volume 139, n° 12S. doi:10.​1016/​j.​annder.​2012.​10.​494.
5.
Zurück zum Zitat Amiri KI, Horton LW, LaFleur BJ, Sosman JA, Richmond A. Augmenting chemosensitivity of malignant melanoma tumors via proteasome inhibition: implication for bortezomib (VELCADE, PS-341) as a therapeutic agent for malignant melanoma. Cancer Res. 2004;64:4912–8.CrossRefPubMed Amiri KI, Horton LW, LaFleur BJ, Sosman JA, Richmond A. Augmenting chemosensitivity of malignant melanoma tumors via proteasome inhibition: implication for bortezomib (VELCADE, PS-341) as a therapeutic agent for malignant melanoma. Cancer Res. 2004;64:4912–8.CrossRefPubMed
6.
Zurück zum Zitat Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma. Am Cancer Soc. 2007;109:455–64. Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma. Am Cancer Soc. 2007;109:455–64.
8.
Zurück zum Zitat Gallerne C, Prola A, Lemaire C. Hsp90 inhibition by PU-H71 induces apoptosis through endoplasmic reticulum stress and mitochondrial pathway in cancer cells and overcomes the resistance conferred by Bcl-2. Biochim Biophys Acta. 1833;2013:1356–66. Gallerne C, Prola A, Lemaire C. Hsp90 inhibition by PU-H71 induces apoptosis through endoplasmic reticulum stress and mitochondrial pathway in cancer cells and overcomes the resistance conferred by Bcl-2. Biochim Biophys Acta. 1833;2013:1356–66.
9.
Zurück zum Zitat Saxena N, Ansari KM, Kumar R, Dhawan A, Dwivedi PD, Das M. Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p53 and p21/WAF1 proteins in skin of mice. Toxicol Appl Pharmacol. 2009;234:192–201.CrossRefPubMed Saxena N, Ansari KM, Kumar R, Dhawan A, Dwivedi PD, Das M. Patulin causes DNA damage leading to cell cycle arrest and apoptosis through modulation of Bax, p53 and p21/WAF1 proteins in skin of mice. Toxicol Appl Pharmacol. 2009;234:192–201.CrossRefPubMed
10.
Zurück zum Zitat Zhou S, Jiang L, Geng C, Cao J, Zhong L. Patulininduced oxidative DNA damage and p53 modulation in HepG2 cells. Toxicon. 2010;55:390–5.CrossRefPubMed Zhou S, Jiang L, Geng C, Cao J, Zhong L. Patulininduced oxidative DNA damage and p53 modulation in HepG2 cells. Toxicon. 2010;55:390–5.CrossRefPubMed
11.
Zurück zum Zitat De Melo FT, De Oliveira IM, Greggio S, Dacosta JC, Guecheva TN, Saffi J, et al. DNA damage in organs of mice treated acutely with patulin, a known mycotoxin. Food Chem Toxicol. 2012;10:3548–55.CrossRef De Melo FT, De Oliveira IM, Greggio S, Dacosta JC, Guecheva TN, Saffi J, et al. DNA damage in organs of mice treated acutely with patulin, a known mycotoxin. Food Chem Toxicol. 2012;10:3548–55.CrossRef
12.
Zurück zum Zitat Kwon O, Soung NK, Thimmegowda NR, Jeong SJ, Jang JH, Moon DO, et al. Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation. Cell Signal. 2012;24:943–50.CrossRefPubMed Kwon O, Soung NK, Thimmegowda NR, Jeong SJ, Jang JH, Moon DO, et al. Patulin induces colorectal cancer cells apoptosis through EGR-1 dependent ATF3 up-regulation. Cell Signal. 2012;24:943–50.CrossRefPubMed
13.
Zurück zum Zitat Ayed-Boussema I, Abassi H, Bouaziz C, Ben Hlima W, Ayed Y, Bacha H. Antioxidative and antigenotoxic effect of vitamin E against patulin cytotoxicity and genotoxicity in HepG2 cells. Environ Toxicol. 2013;28:299–306.CrossRefPubMed Ayed-Boussema I, Abassi H, Bouaziz C, Ben Hlima W, Ayed Y, Bacha H. Antioxidative and antigenotoxic effect of vitamin E against patulin cytotoxicity and genotoxicity in HepG2 cells. Environ Toxicol. 2013;28:299–306.CrossRefPubMed
14.
Zurück zum Zitat Boussabbeh M, Ben Salem I, Prola A, Guilbert A, Bacha H, Abid-Essefi S, Lemaire C. Patulin induces apoptosis through ROS-mediated endoplasmic reticulum stress pathway. Toxicological Sciences. 2015;1–10. doi:10.1093/toxsci/kfu319. Boussabbeh M, Ben Salem I, Prola A, Guilbert A, Bacha H, Abid-Essefi S, Lemaire C. Patulin induces apoptosis through ROS-mediated endoplasmic reticulum stress pathway. Toxicological Sciences. 2015;1–10. doi:10.​1093/​toxsci/​kfu319.
15.
Zurück zum Zitat Ciegler A, Becwith AC, Jackson LK. Teratogenicity of patulin and patulin adducts formed with cysteine. Appl Environ Microbiol. 1976;31:664–7.PubMedPubMedCentral Ciegler A, Becwith AC, Jackson LK. Teratogenicity of patulin and patulin adducts formed with cysteine. Appl Environ Microbiol. 1976;31:664–7.PubMedPubMedCentral
16.
Zurück zum Zitat Osswald H, Frank HK, Komitowski D, Winter H. Long term testing of patulin administer orally to Sprague–Dawley rats and Swiss mice. Food Cosmet Toxicol. 1978;16:243–7.CrossRefPubMed Osswald H, Frank HK, Komitowski D, Winter H. Long term testing of patulin administer orally to Sprague–Dawley rats and Swiss mice. Food Cosmet Toxicol. 1978;16:243–7.CrossRefPubMed
17.
Zurück zum Zitat International Agency for Research on Cancer (IARC), WHO. Some naturally occurring and synthetic food components, furocoumarins and ultraviolet radiation. 1998. International Agency for Research on Cancer (IARC), WHO. Some naturally occurring and synthetic food components, furocoumarins and ultraviolet radiation. 1998.
18.
Zurück zum Zitat Sarray S, Delamarre E, Marvaldi J, El Ayeb M, Marrakchi N, Luis J. Lebectin and lebecetin, two C-type lectins from snake venom, inhibit α5β1 and αv-containing integrins. Matrix Biol. 2007;26:306–13.CrossRefPubMed Sarray S, Delamarre E, Marvaldi J, El Ayeb M, Marrakchi N, Luis J. Lebectin and lebecetin, two C-type lectins from snake venom, inhibit α5β1 and αv-containing integrins. Matrix Biol. 2007;26:306–13.CrossRefPubMed
19.
Zurück zum Zitat Rjiba-Touati K, Ayed-Boussema I, Belarbia A, Azzebi A, Achour A, Bacha H. Protective effect of recombinant human erythropoeitin against cisplatin cytotoxicity and genotoxicity in cultured Vero cells. Exp Toxicol Pathol. 2013;65(1–2):181–7.CrossRefPubMed Rjiba-Touati K, Ayed-Boussema I, Belarbia A, Azzebi A, Achour A, Bacha H. Protective effect of recombinant human erythropoeitin against cisplatin cytotoxicity and genotoxicity in cultured Vero cells. Exp Toxicol Pathol. 2013;65(1–2):181–7.CrossRefPubMed
20.
Zurück zum Zitat Collins AR, Dusinska M, Gedik CM, Stetina R. Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect. 1996;104:465–9.CrossRefPubMedPubMedCentral Collins AR, Dusinska M, Gedik CM, Stetina R. Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect. 1996;104:465–9.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Alves I, Oliveira NG, Laires A, Rodrigues AS, Rueff J. Induction of micronuclei and chromosomal aberrations by themycotoxin patulin in mammalian cells: role of ascorbic acid as a modulator of patulin clastogenicity. Mutagenesis. 2000;15:229–34.CrossRefPubMed Alves I, Oliveira NG, Laires A, Rodrigues AS, Rueff J. Induction of micronuclei and chromosomal aberrations by themycotoxin patulin in mammalian cells: role of ascorbic acid as a modulator of patulin clastogenicity. Mutagenesis. 2000;15:229–34.CrossRefPubMed
22.
Zurück zum Zitat Pfeiffer E, Gross K, Metzler M. Aneuploidogenic and clastogenic potential of the mycotoxins citrinin and patulin. Carcinogenesis. 1998;19:1313–8.CrossRefPubMed Pfeiffer E, Gross K, Metzler M. Aneuploidogenic and clastogenic potential of the mycotoxins citrinin and patulin. Carcinogenesis. 1998;19:1313–8.CrossRefPubMed
23.
Zurück zum Zitat Imaida K, Hirose M, Ogiso T, Kurata Y, Ito N. Quantitative analysis of initiating and promoting activities of five mycotoxins in liver carcinogenesis in rats. Cancer Lett. 1982;16:137–43.CrossRefPubMed Imaida K, Hirose M, Ogiso T, Kurata Y, Ito N. Quantitative analysis of initiating and promoting activities of five mycotoxins in liver carcinogenesis in rats. Cancer Lett. 1982;16:137–43.CrossRefPubMed
24.
Zurück zum Zitat Saxena N, Ansari KM, Kumar R, Chaudhari BP, Dwivedi PD, Das M. Role of mitogen activated protein kinases in skin tumorigenicity of patulin. Toxicol Appl Pharmacol. 2011;257:264–71.CrossRefPubMed Saxena N, Ansari KM, Kumar R, Chaudhari BP, Dwivedi PD, Das M. Role of mitogen activated protein kinases in skin tumorigenicity of patulin. Toxicol Appl Pharmacol. 2011;257:264–71.CrossRefPubMed
27.
Zurück zum Zitat Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8:519–29.CrossRefPubMed Ron D, Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol. 2007;8:519–29.CrossRefPubMed
28.
Zurück zum Zitat Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol. 2012;13:89–102.PubMed Hetz C. The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol. 2012;13:89–102.PubMed
29.
Zurück zum Zitat Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN. Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol. 1993;4:327–32.PubMed Korsmeyer SJ, Shutter JR, Veis DJ, Merry DE, Oltvai ZN. Bcl-2/Bax: a rheostat that regulates an anti-oxidant pathway and cell death. Semin Cancer Biol. 1993;4:327–32.PubMed
Metadaten
Titel
The potential effect of patulin on mice bearing melanoma cells: an anti-tumour or carcinogenic effect?
verfasst von
Manel Boussabbeh
Intidhar Ben Salem
Karima Rjiba-Touati
Chedy Bouyahya
Fadwa Neffati
Mohamed Fadhel Najjar
Hassen Bacha
Salwa Abid-Essefi
Publikationsdatum
30.11.2015
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 5/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4474-z

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