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Acta Parasitologica

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Volume 63, Issue 1


Syphacia muris infection in rats attenuates colorectal carcinogenesis through oxidative stress and gene expression alterations. Implications for modulatory effects by Bryostatin-1

Elsayed I. Salim / Samar F. Harras / Aisha G. Abdalla
  • Zoology Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
  • Faculty of Public Health, Benghazi University, Benghazi, Lybia
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Mohmmed H. Mona
Published Online: 2018-01-17 | DOI: https://doi.org/10.1515/ap-2018-0023


Accumulating evidence suggest that some infectious agents may interfere in the natural progression of neoplasia. This study examined the association between chronic infection with adult Syphacia muris parasites and 1,2-dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats. In addition, the conceivable therapeutic effect of Bryostatin-1, a potent extract of the marine Bryozoan, Bugulane ritina, was investigated against this combined effect.DMH administration has induced aberrant crypt foci (ACF), surrogate biomarkers for colorectal carcinogenesis, while the S. muris infection combined with DMH has significantly increased the total numbers of ACF. Nonetheless, treatment with Bryostatin-1 after infection has significantly reduced the ACF numbers particularly larger ones. This inhibition was concomitant with significant inhibition in the immunohistochemical levels of the ki67, Caspase-3 and IgM levels in colorectal epithelium, as well as serum levels of IgM and IgG. Additionally, treatment with Bryostatin-1 after S. muris + DMH has modulated enzymatic antioxidative markers levels of superoxide dismutase and catalase as well as the non-enzymatic antioxidant markers levels of reduced glutathione, lipid peroxidation, nitric oxide and total antioxidant capacity. Further, treatment with Bryostatin-1 has down-regulated the mRNA expression levels of COX-2 and APC genes in colorectal mucosa. In conclusion, infection with S. muris during colorectal carcinogenesis has significantly modulated the oxidative stress markers in the colorectum, while treatment with Bryostatin-1 has exerted significant curative potential. A mechanism could be explained that Bryostatin-1 treatment has reduced oxidative stress markers activities along with affecting host to parasite immunity possibly leading to changes in the COX-2 and APC expression, retarding cellular proliferation and subsequently reducing the colorectal carcinogenesis events.

Keywords: DMH; Syphacia muris; Bryostatin-1; ROS; Rat; COX-2; APC; IgG; IgM; Ki67; Caspase-3; ACF


  • Alberts B., Johnson A., Lewis J., Walter P., Raff M., Roberts K., et al. 2002. Chapter 24. Molecular Biology of the Cell (4th ed.). New York: Garland Science; Molecular Biology of the Cell, 4th edition. ISBN-10: 0-8153-3218-1ISBN-10: 0-8153-4072-9Google Scholar

  • Alkon D.L., Hongpaisan J., Sun M.K. 2017. Effects of chronic bryostatin-1 on treatment-resistant depression in rats. European Journal of Pharmacology, PII, S0014-2999(17)30304-7. CrossrefWeb of ScienceGoogle Scholar

  • Atari-Hajipirloo S., Nikanfar S., Heydari A., Noori F., Kheradmand F. 2016. The effect of celecoxib and its combination with imatinib on human HT-29 colorectal cancer cells: Involvement of COX-2, Caspase-3, VEGF and NF-κB genes expression. Cellular and Molecular Biology, 62, 68–74Google Scholar

  • Balaji C., Muthukumaran J., Nalini N. 2015. Effect of sinapic acid on 1,2 dimethylhydrazine induced aberrant crypt foci, biotransforming bacterial enzymes and circulatory oxidative stress status in experimental rat colon carcinogenesis. Bratislavske Lekarske Listy, 116, 560–6Web of SciencePubMedGoogle Scholar

  • Bastide N.M., Naud N., Nassy G., Vendeuvre J.L., Taché S., Guéraud F., et al. 2017. Red Wine and Pomegranate Extracts Suppress Cured Meat Promotion of Colonic Mucin-Depleted Foci in Carcinogen-Induced Rats. Nutrition and Cancer, 69, 289–298. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Beutler E. (Ed.) 1982. Catalase, In: Red Cell Metabolism, a Manual of Biochemical Methods, Grune and Stratton New York, pp.105–106Google Scholar

  • Breen L.D., Pučić-Baković M., Vučković F., Reiding K., Trbojević-Akmačić I., Šrajer Gajdošik M., et al. 2016. IgG and IgM glycosylation patterns in patients undergoing image-guided tumor ablation. Biochimica et Biophysica Acta, 1860, 1786–94. CrossrefPubMedGoogle Scholar

  • Burkhart C.N., Burkhart C.G. 2005. Assessment of frequency, transmission, and genitourinary complications of enterobiasis (pinworms). International Journal of Dermatology, 44, 837–40. CrossrefPubMedGoogle Scholar

  • Chahid K., Laglaoui A., Zantar S., Ennabili A. 2015. Antioxidant-enzyme reaction to the oxidative stress due to alpha-cypermethrin, chlorpyriphos, and pirimicarb in tomato (Lycopersicon esculentum Mill.). Environmental Science and Pollution Research, 22, 18115–26. CrossrefWeb of ScienceGoogle Scholar

  • Davidson S.K., Allen S.W., Lim G.E., Anderson, C.M., Haygood, M.G. 2001. Evidence for the Biosynthesis of Bryostatins by the Bacterial Symbiont “Candidatus Endobugula sertula” of the Bryozoan Bugula neritina. Applied and Environmental Microbiology, 67, 4531–4537. CrossrefPubMedGoogle Scholar

  • DeWitt M., Johnson R.L., Snyder P., Fleet J.C. 2015. The effect of 1,25 dihydroxyvitamin D treatment on the mRNA levels of β catenin target genes in mice with colonic inactivation of both APC alleles. The Journal of Steroid Biochemistry and Molecular Biology, 148, 103–110. CrossrefWeb of SciencePubMedGoogle Scholar

  • Etcheberrigaray R., Tan M., Dewachter I., Kuipéri C., Van der Auwera I., Wera S., et al.. 2004. Therapeutic effects of PKC activators in Alzheimer’s disease transgenic mice. Proceedings of the National Academy of Sciences USA, 101, 11141–11146. CrossrefGoogle Scholar

  • Fijneman R.J., Peham J.R., van de Wiel M.A., Meijer G.A., Matise I., Velcich A., et al. 2008. Expression of Pla2g2a prevents carcinogenesis in Muc2-deficient mice. Cancer Science, 99, 2113–9. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Hale K.J., Manviazar S. 2010. New approaches to the Total Synthesis of Bryostatin Antitumor Macrolides. ChemistryAn Asian Journal, 5, 704–54. CrossrefGoogle Scholar

  • Hanley M.P., Hahn M.A., Li A.X., Wu X., Lin J., Wang J., et al. 2017. Genome-wide DNA methylation profiling reveals cancer-associated changes within early colonic neoplasia. Oncogene. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Ince S., Kozan E., Kucukkurt I., Bacak E. 2010. The effect of levamisole and levamisole+vitamin C on oxidative damage in rats naturally infected with Syphacia muris. Experimental Parasitology, 124, 448–52. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Jacqueline C., Tasiemski A., Sorci G., Ujvari B., Maachi F., Missá D., et al., 2017. Infections and cancer: the “fifty shades of immunity hypothesis”. BMC Cancer, 17, 257. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Jaggi M., Chauhan S.C., Du C., Balaji K.C. 2008. Bryostatin 1 modulates beta-catenin subcellular localization and transcription activity through protein kinase D1 activation. Molecular Cancer Therapeutics, 7, 2703–12. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Janakiram N.B., Rao C.V. 2014. Inflammation and Cancer, Advances in Experimental Medicine and Biology 816, 25–52, CrossrefGoogle Scholar

  • Jiangbo Z., Xuying W., Yuping Z., Xili M., Yiwen Z., Tianbao Z. 2010. Toxicity of bryostatin-1 on the embryo-fetal development of Sprague-Dawley rats. Birth Defects Research, 89, 171–174. CrossrefGoogle Scholar

  • Kello M., Drutovic D., Pilatova M.B., Tischlerova V., Perjesi P., Mojzis J. 2016. Chalcone derivatives cause accumulation of colon cancer cells in the G2/M phase and induce apoptosis. Life Science, 150, 32–8. CrossrefGoogle Scholar

  • Mutter R., Wills M. 2000. Chemistry and clinical biology of the bryostatins. Bioorganic & Medicinal Chemistry, 8, 1841–1860PubMedCrossrefGoogle Scholar

  • Kosik-Bogacka D.I., Baranowska-Bosiacka I., Kolasa-Wolosiuk A., Lanocha-Arendarczyk N., Gutowska I, Korbecki J., et al. 2016. The inflammatory effect of infection with Hymenolepis diminuta via the increased expression and activity of COX-1 and COX-2 in the rat jejunum and colon. Experimental Parasitology, 169, 69–76. CrossrefWeb of SciencePubMedGoogle Scholar

  • Lesko A.C., Goss K.H., Yang F.F., Schwertner A., Hulur I., Onel K., et al. 2015. The APC tumor suppressor is required for epithelial cell polarization and three-dimensional morphogenesis. Biochimica et Biophysica Acta, 1853, 711–23. CrossrefPubMedGoogle Scholar

  • Livak K.J., Schmittgen T.D. 2001. Analysis of relative gene expression data using real time quantitative PCR, the 2DDCT. Methods, 25, 402–408. CrossrefPubMedGoogle Scholar

  • Montgomery J.F., Hum S. 1995. Field diagnosis of nitrite poisoning in cattle by testing aqueous humor samples with urine test strips. Veterinary Record, 137, 593–594Google Scholar

  • Notarnicola M., Tutino V., De Nunzio V., Dituri F., Caruso M.G., Giannelli G. 2017. Dietary ω-3 Polyunsaturated Fatty Acids Inhibit Tumor Growth in Transgenic ApcMin/+ Mice, Correlating with CB1 Receptor Up-Regulation. International Journal of Molecular Sciences, 18, E485. CrossrefGoogle Scholar

  • Perec-Matysiak A., Okulewicz A., Hildebrand J., Zalesny G. 2006. Helminth parasites of laboratory mice and rats. Wiadomości Parazytologiczne, 52, 99–102PubMedGoogle Scholar

  • Peterson M.R., Weidner N. 2011. Gastrointestinal neoplasia associated with bowel parasitosis: real or imaginary?, Journal of Tropical Medicine, 234254. CrossrefPubMedGoogle Scholar

  • Plummer M., de Martel C., Vignat J., Ferlay J., Bray F., Franceschi S. 2016. Global burden of cancers attributable to infections in 2012: a synthetic analysis. Lancet Global Health, 4, e609–16. CrossrefWeb of ScienceGoogle Scholar

  • Rana T., Bera A.K., Das S., Bhattacharya D., Pan D., Das S.K. 2016. Inhibition of Oxidative Stress and Enhancement of Cellular Activity by Mushroom Lectins in Arsenic Induced Carcinogenesis. Asian Pacific Journal of Cancer Prevention, 17, 4185–4197Google Scholar

  • Salim, E.I., Morimura K., Menesi A., El-Lity M., Fukushima S. and Wanibuchi H. 2008. Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with Schistosomiasis. International Journal of Cancer, 123, 601–8. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Shiraishi N., Ohta Y., Nishikimi M. 2000. The octapeptide repeat region of prion protein binds Cu(II) in the redox inactive states. Biochemical and Biophysical Research Communications, 267, 398–402. CrossrefGoogle Scholar

  • Sinha A.K. 1972. Colorimetric assay of catalase. Analytical Biochemistry, 47, 389–394CrossrefPubMedGoogle Scholar

  • Staff C., Magnusson C.G., Hojjat-Farsangi M., Mosolits S., Liljefors M., Frödin J.E. 2012. Induction of IgM, IgA and IgE antibodies in colorectal cancer patients vaccinated with a recombinant CEA protein. Journal of Clinical Immunology, 32, 855–65. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Theodoratou E., Thaçi K., Agakov F., Timofeeva M.N., Štambuk J., Pučić-Baković M., et al. 2016. Glycosylation of plasma IgG in colorectal cancer prognosis. Scientific Reports, 6, 28098. CrossrefWeb of ScienceGoogle Scholar

  • Su L.K., Vogelstein B., Kinzler K.W. 1993. Association of the APC tumor suppressor protein with catenins, Science, 262, 1734–1737CrossrefPubMedGoogle Scholar

  • Sun M.K. and Alkon D.L. 2008. Synergistic effects of chronic bryostatin-1 and alpha-tocopherol on spatial learning and memory in rats. European Journal of Pharmacology, 584, 328–37. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Wang L., Hu T., Shen J., Zhang L., Chan R.L., et al. 2015. Dihydrotanshinone I induced apoptosis and autophagy through caspase dependent pathway in colon cancer. Phytomedicine, 22, 1079–87. CrossrefPubMedWeb of ScienceGoogle Scholar

  • Yamasaki T., Takahashi A., Pan J., Yamaguchi N., Yokoyama K.K. 2009. Phosphorylation of Activation Transcription Factor-2 at Serine 121 by Protein Kinase C Controls c-Jun-mediated Activation of Transcription. The Journal of Biological Chemistry, 284, 8567–81. CrossrefPubMedGoogle Scholar

  • Ye B., Yu-Xia Zhang Y-X., Fei Yang F., Hong-Lei Chen H-L., et al. 2007. Induction of lung lesions in Wistar rats by 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate. BMC Cancer, 7, 90. CrossrefGoogle Scholar

  • Yoshioka T., Kawada K., Shimada T., Mori M. 1979. Lipid peroxidation in maternal and cord blood and protective mechanism against activated oxygen toxicity in the blood. American Journal of Obstetrics & Gynecology, 135, 372CrossrefGoogle Scholar

  • Zoon C.K., Wan W., Graham L., Bear H.D. 2017. Expansion of T Cells with Interleukin-21 for Adoptive Immunotherapy of Murine Mammary Carcinoma. International Journal of Molecular Sciences, 18, E270. CrossrefPubMedWeb of ScienceGoogle Scholar

About the article

Received: 2017-07-28

Revised: 2017-11-20

Accepted: 2017-11-30

Published Online: 2018-01-17

Published in Print: 2018-03-26

Citation Information: Acta Parasitologica, Volume 63, Issue 1, Pages 198–209, ISSN (Online) 1896-1851, ISSN (Print) 1230-2821, DOI: https://doi.org/10.1515/ap-2018-0023.

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