Journal of Oncology Research and Therapy (ISSN: 2574-710X)

Research Article

The Antitumor Molecule TPEN Inhibits the Self-Renewal Potential of 5-Fluorouracil Resistant Colorectal Cancer Stem Cells

Fata Akl1≠, Zaynab Fatfat2≠, Soha Faraj1, Farah Ballout2, Maamoun Fatfat2, Hala Gali- Muhtasib2,3, Hala Khalife1*

1Rammal Rammal Laboratory (ATAC Group), Faculty of Sciences, Lebanese University, Beirut, Lebanon

2Department of Biology, American University of Beirut, Beirut, Lebanon

3Department of Anatomy, Cell Biology and Physiological Sciences and Center for Drug Discovery, American University of Beirut, Beirut, Lebanon

equal contribution

Corresponding Author*: Hala Khalife, Rammal Rammal Laboratory (ATAC Group), Faculty of Sciences, Lebanese University, Lebanon.

Received Date: 24 August, 2021

Accepted Date: 08 September, 2021

Published Date: 14 September, 2021

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 self- renewal 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.

Keywords: 5-Fluorouracil chemoresistance; Tumor relapse; Colorectal cancer stem cells; Colonospheres; Therapeutics; TPEN


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