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Volume 20, Issue 1
  • ISSN: 1574-888X
  • E-ISSN: 2212-3946

Abstract

Background

One of the main reasons for cancer resistance to chemotherapy is the presence of cancer stem cells (CSCs) in cancer tissues. It is also believed that CSCs are the unique originators of all tumor cells. On the other hand, the Epithelial-Mesenchymal Transition pathway (EMT) can act as the main agent of metastasis. Therefore, it is possible that targeting CSCs as well as the EMT pathway could help in cancer therapy. Considering that CSCs constitute only a small percentage of the total tumor mass, enrichment before study is necessary. In our previous study, CSCs were enriched in the human colon cancer cell line HT29 by induction of EMT. These CSC-enriched HT29 cells with mesenchymal morphology were named “HT29-shE”. In the present study, these cells were used to investigate the effect of Pioglitazone (Pio) and Cetuximab (Cet) in order to find CSC and EMT targeting agents.

Methods

The viability and IC rate of cells treated with different concentrations of Pio and Cet were evaluated using the MTT test. EMT and CSC markers and cell morphology were assessed in Pio and Cet treated and untreated HT29-shE cells using flow cytometry, realtime PCR, immunocytochemistry, and microscopic monitoring.

Results

The findings showed that Pio and Cet at concentrations of 250 µM and 40 µg/ml, respectively, decrease cell viability by 50%. Also, they were able to reduce the expression of CSC markers (CD133 and CD44) in the CSC enriched HT29 cell line. Furthermore, Pio and Cet could efficiently reduce the expression of vimentin as a mesenchymal marker and significantly upregulate the expression of E-cadherin as an epidermal marker of EMT and its reverse mesenchymal- to-epithelial transition (MET). In addition, the mesenchymal morphology of HT29-shE changed into epithelial morphology after Cet treatment.

Conclusion

Pio and Cet could inhibit EMT and reduce CSC markers in the EMT induced/CSC enriched cell line. We expect that focus on finding EMT/CSC-targeting agents like these drugs can be helpful for cancer treatment.

© 2025 Bentham Science Publishers
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2024-01-31
2025-01-22

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References

  1. FreemanH.J. Early stage colon cancer.World J. Gastroenterol.201319468468847310.3748/wjg.v19.i46.846824379564
     [Google Scholar]
  2. ColakS. MedemaJ.P. Cancer stem cells - important players in tumor therapy resistance.FEBS J.2014281214779479110.1111/febs.1302325158828
     [Google Scholar]
  3. DallasN.A. XiaL. FanF. GrayM.J. GaurP. van BurenG.II SamuelS. KimM.P. LimS.J. EllisL.M. Chemoresistant colorectal cancer cells, the cancer stem cell phenotype, and increased sensitivity to insulin-like growth factor-I receptor inhibition.Cancer Res.20096951951195710.1158/0008‑5472.CAN‑08‑202319244128
     [Google Scholar]
  4. FanF. SamuelS. EvansK.W. LuJ. XiaL. ZhouY. SceusiE. TozziF. YeX.C. ManiS.A. EllisL.M. Overexpression of Snail induces epithelial-mesenchymal transition and a cancer stem cell- like phenotype in human colorectal cancer cells.Cancer Med.20121151610.1002/cam4.423342249
     [Google Scholar]
  5. JohariB. RezaeejamH. MoradiM. TaghipourZ. SaltanatpourZ. MortazaviY. NasehiL. Increasing the colon cancer cells sensitivity toward radiation therapy via application of Oct4–Sox2 complex decoy oligodeoxynucleotides.Mol. Biol. Rep.20204796793680510.1007/s11033‑020‑05737‑432865703
     [Google Scholar]
  6. JohariB. Myc decoy oligodeoxynucleotide inhibits growth and modulates differentiation of mouse embryonic stem cells as a model of cancer stem cells.Anti-Cancer Agents Med. Chem.2017171317861795
     [Google Scholar]
  7. ManiS.A. GuoW. LiaoM.J. EatonE.N. AyyananA. ZhouA.Y. BrooksM. ReinhardF. ZhangC.C. ShipitsinM. CampbellL.L. PolyakK. BriskenC. YangJ. WeinbergR.A. The epithelial-mesenchymal transition generates cells with properties of stem cells.Cell2008133470471510.1016/j.cell.2008.03.02718485877
     [Google Scholar]
  8. SiposF. GalambO. Epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions in the colon.World J. Gastroenterol.201218760160810.3748/wjg.v18.i7.60122363130
     [Google Scholar]
  9. SaltanatpourZ. JohariB. AlizadehA. LotfiniaM. Majidzadeh-AK. NikbinB. KadivarM. Enrichment of cancer stem-like cells by the induction of epithelial-mesenchymal transition using lentiviral vector carrying E-cadherin shRNA in HT29 cell line.J. Cell. Physiol.201923412229352294610.1002/jcp.2885531111504
     [Google Scholar]
  10. SantistebanM. ReimanJ.M. AsieduM.K. BehrensM.D. NassarA. KalliK.R. HaluskaP. IngleJ.N. HartmannL.C. ManjiliM.H. RadiskyD.C. FerroneS. KnutsonK.L. Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells.Cancer Res.20096972887289510.1158/0008‑5472.CAN‑08‑334319276366
     [Google Scholar]
  11. SatelliA. LiS. Vimentin in cancer and its potential as a molecular target for cancer therapy.Cell. Mol. Life Sci.201168183033304610.1007/s00018‑011‑0735‑121637948
     [Google Scholar]
  12. RinnJ.L. BondreC. GladstoneH.B. BrownP.O. ChangH.Y. Anatomic demarcation by positional variation in fibroblast gene expression programs.PLoS Genet.200627e11910.1371/journal.pgen.002011916895450
     [Google Scholar]
  13. CastorA. NilssonL. Åstrand-GrundströmI. BuitenhuisM. RamirezC. AndersonK. StrömbeckB. GarwiczS. BékássyA.N. SchmiegelowK. LausenB. HoklandP. LehmannS. JuliussonG. JohanssonB. JacobsenS.E.W. Distinct patterns of hematopoietic stem cell involvement in acute lymphoblastic leukemia.Nat. Med.200511663063710.1038/nm125315908956
     [Google Scholar]
  14. GuptaP.B. OnderT.T. JiangG. TaoK. KuperwasserC. WeinbergR.A. LanderE.S. Identification of selective inhibitors of cancer stem cells by high-throughput screening.Cell2009138464565910.1016/j.cell.2009.06.03419682730
     [Google Scholar]
  15. MaghsoodF. JohariB. RohaniM. MadanchiH. SaltanatpourZ. KadivarM. Anti-proliferative and anti-metastatic potential of high molecular weight secretory molecules from probiotic Lactobacillus reuteri cell-free supernatant against human colon cancer stem- like cells (HT29-ShE).Int. J. Pept. Res. Ther.20202642619263110.1007/s10989‑020‑10049‑z
     [Google Scholar]
  16. ZeunerA. TodaroM. StassiG. De MariaR. Colorectal cancer stem cells: From the crypt to the clinic.Cell Stem Cell201415669270510.1016/j.stem.2014.11.01225479747
     [Google Scholar]
  17. AkbarzadehM. MaroufiN.F. TazehkandA.P. AkbarzadehM. BastaniS. SafdariR. FarzaneA. FattahiA. NejabatiH.R. NouriM. SamadiN. Current approaches in identification and isolation of cancer stem cells.J. Cell. Physiol.20192349147591477210.1002/jcp.2827130741412
     [Google Scholar]
  18. SavagnerP. The epithelial-mesenchymal transition (EMT) phenomenon.Ann. Oncol.201021Suppl. 7vii89vii9210.1093/annonc/mdq29220943648
     [Google Scholar]
  19. SinghA. SettlemanJ. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer.Oncogene201029344741475110.1038/onc.2010.21520531305
     [Google Scholar]
  20. CufíS. Vazquez-MartinA. Oliveras-FerrarosC. Martin-CastilloB. JovenJ. MenendezJ.A. Metformin against TGFβ-induced epithelial-to-mesenchymal transition (EMT): From cancer stem cells to aging-associated fibrosis.Cell Cycle20109224461446810.4161/cc.9.22.1404821088486
     [Google Scholar]
  21. ReyaT. Stem cells, cancer, and cancer stem cells.Nature200141468591501110.1038/35102167
     [Google Scholar]
  22. FangX. CaiY. LiuJ. WangZ. WuQ. ZhangZ. YangC.J. YuanL. OuyangG. Twist2 contributes to breast cancer progression by promoting an epithelial-mesenchymal transition and cancer stem-like cell self-renewal.Oncogene201130474707472010.1038/onc.2011.18121602879
     [Google Scholar]
  23. BigdelouZ. MortazaviY. SaltanatpourZ. AsadiZ. KadivarM. JohariB. Role of Oct4–Sox2 complex decoy oligodeoxynucleotides strategy on reverse epithelial to mesenchymal transition (EMT) induction in HT29-ShE encompassing enriched cancer stem-like cells.Mol. Biol. Rep.20204731859186910.1007/s11033‑020‑05280‑232016633
     [Google Scholar]
  24. CiaramellaV. SassoF.C. Di LielloR. CorteC.M.D. BarraG. ViscardiG. EspositoG. SparanoF. TroianiT. MartinelliE. OrdituraM. De VitaF. CiardielloF. MorgilloF. Activity and molecular targets of pioglitazone via blockade of proliferation, invasiveness and bioenergetics in human NSCLC.J. Exp. Clin. Cancer Res.201938117810.1186/s13046‑019‑1176‑131027492
     [Google Scholar]
/content/journals/cscr/10.2174/011574888X283318240118111822
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Effect of Pioglitazone and Cetuximab on Colon Cancer Stem-like Cell (CCSLCs) Properties
Curr Stem Cell Res Ther 20, 83 (2025); https://doi.org/10.2174/011574888X283318240118111822
/content/journals/cscr/10.2174/011574888X283318240118111822
/content/journals/cscr/10.2174/011574888X283318240118111822
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  • Article Type:     Research Article
Keyword(s): Cancer stem cells (CSCs); cetuximab; colon cancer stem cell; CSC targeting drugs; EMT; EMT targeting drugs; pioglitazone

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