PMID- 29439258 OWN - NLM STAT- MEDLINE DCOM- 20180319 LR - 20190212 IS - 1421-9778 (Electronic) IS - 1015-8987 (Linking) VI - 45 IP - 3 DP - 2018 TI - Bone Marrow Cell Therapy on 1,2-Dimethylhydrazine (DMH)-Induced Colon Cancer in Rats. PG - 1072-1083 LID - 10.1159/000487349 [doi] AB - BACKGROUND/AIMS: Stem cell based therapies are being under focus due to their possible role in treatment of various tumors. Bone marrow stem cells believed to have anticancer potential and are preferred for their activities by stimulating the immune system, migration to the site of tumor and ability for inducting apoptosis in cancer cells. The current study was aimed to investigate the tumor suppressive effects of bone marrow cells (BMCs) in 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats. METHODS: The rats were randomly allocated into four groups: control, BMCs alone, DMH alone and BMCs with DMH. BMCs were injected intrarectally while DMH was injected subcutaneously at 20 mg/kg body weight once a week for 15 weeks. Histopathological examination and gene expression of survivin, beta-catenin and multidrug resistance-1 (MDR-1) by real-time reverse transcription-polymerase chain reaction (RT-PCR) in rat colon tissues. This is in addition to oxidative stress markers in colon were performed across all groups. RESULTS: The presence of aberrant crypt foci was reordered once histopathological examination of colon tissue from rats which received DMH alone. Administration of BMCs into rats starting from zero-day of DMH injection improved the histopathological picture which showed a clear improvement in mucosal layer, few inflammatory cells infiltration periglandular and in the lamina propria. Gene expression in rat colon tissue demonstrated that BMCs down-regulated survivin, beta-catenin, MDR-1 and cytokeratin 20 genes expression in colon tissues after colon cancer induction. Amelioration of the colon status after administration of MSCs has been evidenced by a major reduction of lipid peroxidation, nitric oxide, and increasing of glutathione content and superoxide dismutase along with catalase activities. CONCLUSION: Our findings demonstrated that BMCs have tumor suppressive effects in DMH-induced colon cancer as evidenced by down-regulation of survivin, beta-catenin, and MDR-1 genes and enhancing the antioxidant activity. CI - (c) 2018 The Author(s). Published by S. Karger AG, Basel. FAU - El-Khadragy, Manal F AU - El-Khadragy MF AD - Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia. AD - Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt. FAU - Nabil, Heba M AU - Nabil HM AD - National Center for Radiation Research and Technology, Atomic Energy Authority (AEA), Cairo, Egypt. FAU - Hassan, Basmaa N AU - Hassan BN AD - Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt. FAU - Tohamy, Amany A AU - Tohamy AA AD - Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt. FAU - Waaer, Hanaa F AU - Waaer HF AD - National Center for Radiation Research and Technology, Atomic Energy Authority (AEA), Cairo, Egypt. FAU - Yehia, Hany M AU - Yehia HM AD - Department of Food Science and Nutrition, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia. AD - Department of Food Science and Nutrition, Faculty of Home Economics, Helwan University, Cairo, Egypt. FAU - Alharbi, Afra M AU - Alharbi AM AD - Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia. FAU - Moneim, Ahmed Esmat Abdel AU - Moneim AEA AD - Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt. LA - eng PT - Journal Article DEP - 20180207 PL - Germany TA - Cell Physiol Biochem JT - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology JID - 9113221 RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) RN - 0 (Birc5 protein, rat) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Survivin) RN - 0 (beta Catenin) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.11.1.6 (Catalase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - GAN16C9B8O (Glutathione) RN - IX068S9745 (1,2-Dimethylhydrazine) SB - IM MH - 1,2-Dimethylhydrazine/toxicity MH - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics/metabolism MH - Aberrant Crypt Foci/pathology MH - Animals MH - Bone Marrow Cells/cytology MH - *Bone Marrow Transplantation MH - Catalase/metabolism MH - Colon/metabolism/pathology MH - Colonic Neoplasms/chemically induced/pathology/*therapy MH - Down-Regulation MH - Glutathione/metabolism MH - Lipid Peroxidation MH - Male MH - Mice MH - Microtubule-Associated Proteins/genetics/metabolism MH - Nitric Oxide/metabolism MH - Oxidative Stress MH - Rats MH - Rats, Wistar MH - Superoxide Dismutase/metabolism MH - Survivin MH - beta Catenin/genetics/metabolism OTO - NOTNLM OT - 1,2-Dimethylhydrazine OT - Bone marrow cells OT - Colon cancer OT - Cytokeratin 20 OT - Oncogenes EDAT- 2018/02/14 06:00 MHDA- 2018/03/20 06:00 CRDT- 2018/02/14 06:00 PHST- 2017/08/12 00:00 [received] PHST- 2017/12/10 00:00 [accepted] PHST- 2018/02/14 06:00 [pubmed] PHST- 2018/03/20 06:00 [medline] PHST- 2018/02/14 06:00 [entrez] AID - 000487349 [pii] AID - 10.1159/000487349 [doi] PST - ppublish SO - Cell Physiol Biochem. 2018;45(3):1072-1083. doi: 10.1159/000487349. Epub 2018 Feb 7.