@Article{biocell.2021.015464,
AUTHOR = {ATTALLA F. EL-KOTT, AYMAN E. EL-KENAWY, EMAN R. ELBEALY, ALI S. ALSHEHRI, HEBA S. KHALIFA, MASHAEL MOHAMMED BIN-MEFERIJ, EHAB E. MASSOUD, AMIRA M. ALRAMLAWY},
TITLE = {Exendin-4 inhibits the survival and invasiveness of two colorectal cancer cell lines via suppressing GS3Kβ/β-catenin/NF-κB axis through activating SIRT1},
JOURNAL = {BIOCELL},
VOLUME = {45},
YEAR = {2021},
NUMBER = {5},
PAGES = {1337--1353},
URL = {http://www.techscience.com/biocell/v45n5/43082},
ISSN = {1667-5746},
ABSTRACT = {This study examined if the anti-tumorigenesis effect of Exendin-4 in HT29 and HCT116 colorectal
cancer (CRC) involves modulation of SIRT1 and Akt/GSR3K/β-catenin/NF-κB axis. HT29 and HCT116 cells were
treated either with increasing levels of Exendin-4 (0.0-200 µM) or with Exendin-4 (at its IC<sub>50</sub>) in the presence or
absence of EX-527 (10 µM/a selective SIRT1 inhibitor) or Exendin-4 (9-39) amide (E (9-39) A) (1 µM/an Exendin-4
antagonist). In a dose-dependent manner, Exendin-4 inhibited cell survival, but enhanced levels of lactate
dehydrogenase (LDH) and single-stranded DNA (ssDNA) in both HT29 and HCT116. In both cell lines and at it has
an IC<sub>50</sub> (45 µM for HT29 and 35 µM for HCT1165), Exendin-4 also significantly reduced cell survival, migration, and
invasion of both cell types, with no effect on the expression GLP-1 receptors (GLPRs) nor of the activity of Akt. At
these doses, Exendin-4 also increased the expression of SIRT1 but reduced the acetylation of NF-κB and the
expression of Bax and cleaved caspase-3 and in both cell lines. Concomitantly, protein levels of p-GS3Kβ (Ser<sup>9</sup>
), total
and acetylated β-catenin, and Anix2 were significantly decreased, but levels of p-GS3Kβ (Ser<sup>9</sup>
) and p-β-catenin
(Ser<sup>33/37</sup>/Thr<sup>41</sup>) were significantly increased in both HT29 and HCT116-exendin-4 treated cells. All the effects exerted
by Exendin-4 were completely prevented by Ex527 or E (9-39) A. In conclusion, Exendin-4 suppresses the
tumorigenesis of HT29 and HCT116 CRC cell activation of GS3Kβ-induced inhibition of β-catenin and NF-κβ in a
SIRT1-dependent mechanism.},
DOI = {10.32604/biocell.2021.015464}
}