%0 Journal Article %1 akl2021antitumor %A Akl, Fata %A Fatfat, Zaynab %A Faraj, Soha %A Ballout, Farah %A Fatfat, Maamoun %A Gali-Muhtasib, Hala %A Khalife, Hala %D 2021 %J Journal of Oncology Research and Therapy (ISSN: 2574-710X) %K 5-Fluorouracilchemoresistance Colonospheres Colorectalcancerstemcells TPEN Therapeutics Tumorrelapse %P 7 %R 10.29011/2574-710X.010111 %T The Antitumor Molecule TPEN Inhibits the Self-Renewal Potential of 5-Fluorouracil Resistant Colorectal Cancer Stem Cells %U https://www.gavinpublishers.com/article/view/the-antitumor-molecule-tpen-inhibits-the-self-renewal-potential-of-5-fluorouracil-resistant-colorectal-cancer-stem-cells %V 5 %X Background: The major causes of treatment failure and mortality in patients with colorectal cancer are the high recurrence rates and the drug resistance to the conventional chemotherapeutic agent 5-fluorouracil (5-FU). This resistance is greatly associated with a chemoresistant population of self-renewing cancer stem cells (CSCs). The antitumor molecule TPEN has been found to be effective against several cancers including colon cancer in vitro and in vivo. However, its effect on CSCs has not been evaluated yet. Here, we investigated the ability of TPEN to overcome chemoresistance and prevent cancer recurrence by targeting the selfrenewal potential of colorectal CSCs. Methods: MTT assay was used to assess TPEN effect on the viability of 5-FU resistant colorectal cancer cells cultured in 2D monolayers. Sphere-formation and propagation assays were performed to assess the efficacy of TPEN on CSCs enriched from 5-FU sensitive and resistant colon cancer cell lines in 3D cultures over several generations Results: Our data showed that TPEN dose-dependently reduced the viability of 5-FU resistant colon cancer cells in 2D cell cultures. In 3D cultures, results showed that TPEN reduced the self-renewal capacity of CSCs derived from both cell lines over five generations. In addition, TPEN reduced the expression level of stem cell marker CD44 in colonospheres derived from both cell lines at generation 1.Conclusion: Our results suggest that TPEN could be a potent therapeutic agent for eradicating and preventing the re-emergence of colorectal tumors.

@article{akl2021antitumor, abstract = {Background: The major causes of treatment failure and mortality in patients with colorectal cancer are the high recurrence rates and the drug resistance to the conventional chemotherapeutic agent 5-fluorouracil (5-FU). This resistance is greatly associated with a chemoresistant population of self-renewing cancer stem cells (CSCs). The antitumor molecule TPEN has been found to be effective against several cancers including colon cancer in vitro and in vivo. However, its effect on CSCs has not been evaluated yet. Here, we investigated the ability of TPEN to overcome chemoresistance and prevent cancer recurrence by targeting the selfrenewal potential of colorectal CSCs. Methods: MTT assay was used to assess TPEN effect on the viability of 5-FU resistant colorectal cancer cells cultured in 2D monolayers. Sphere-formation and propagation assays were performed to assess the efficacy of TPEN on CSCs enriched from 5-FU sensitive and resistant colon cancer cell lines in 3D cultures over several generations Results: Our data showed that TPEN dose-dependently reduced the viability of 5-FU resistant colon cancer cells in 2D cell cultures. In 3D cultures, results showed that TPEN reduced the self-renewal capacity of CSCs derived from both cell lines over five generations. In addition, TPEN reduced the expression level of stem cell marker CD44 in colonospheres derived from both cell lines at generation 1.Conclusion: Our results suggest that TPEN could be a potent therapeutic agent for eradicating and preventing the re-emergence of colorectal tumors.}, added-at = {2021-11-24T12:12:00.000+0100}, author = {Akl, Fata and Fatfat, Zaynab and Faraj, Soha and Ballout, Farah and Fatfat, Maamoun and Gali-Muhtasib, Hala and Khalife, Hala}, biburl = {https://www.bibsonomy.org/bibtex/26070e5ab1bb0e328762f061bb315ed0b/alyssacarter}, doi = {10.29011/2574-710X.010111}, interhash = {b78b95b1027fe3906dff3599f0369d9e}, intrahash = {6070e5ab1bb0e328762f061bb315ed0b}, issn = {2574-710X}, journal = {Journal of Oncology Research and Therapy (ISSN: 2574-710X)}, keywords = {5-Fluorouracilchemoresistance Colonospheres Colorectalcancerstemcells TPEN Therapeutics Tumorrelapse}, language = {ENGLISH}, month = {September}, pages = 7, timestamp = {2021-11-24T12:12:00.000+0100}, title = {The Antitumor Molecule TPEN Inhibits the Self-Renewal Potential of 5-Fluorouracil Resistant Colorectal Cancer Stem Cells}, url = {https://www.gavinpublishers.com/article/view/the-antitumor-molecule-tpen-inhibits-the-self-renewal-potential-of-5-fluorouracil-resistant-colorectal-cancer-stem-cells}, volume = 5, year = 2021 }