Open Access

Paeonol exerts anti‑tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/β‑catenin signaling pathway

  • Authors:
    • Li‑Hua Liu
    • Ren‑Jie Shi
    • Zhi‑Cheng Chen
  • View Affiliations

  • Published online on: June 4, 2020     https://doi.org/10.3892/ijmm.2020.4629
  • Pages: 675-684
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Paeonol is a simple phenolic compound isolated from herbal root bark, which has been reported to possess numerous biological and pharmacological characteristics, including a desirable anti‑tumor effect. To date, the effect of paeonol against colorectal cancer (CRC) cells is yet to be fully elucidated. Therefore, the present study aimed to identify the underlying mechanism via which paeonol exerts its anti‑tumor activity on HCT116 cells. After incubation with various concentrations of paeonol (7.8125, 15.625, 31.25, 62.5, 125, 250 and 500 µg/ml), the inhibitory effect of paeonol on cell viability was assessed using a Cell Counting Kit‑8 assay. Cell apoptosis and cell cycle distribution were measured using flow cytometry. Moreover, caspase activity was measured using a colorimetric caspase assay. Luciferase assay was also used to determine the β‑catenin‑mediated transcriptional activity of T‑cell specific transcription factor/lymphoid‑enhancer binding factor (TCF/LEF), and western blotting analysis was performed to measure the related expression of proteins. The results indicated that paeonol exhibited a notable effect against HCT116 cells by inducing G0/G1‑phase arrest, as demonstrated by downregulation of the cell cycle regulators cyclin‑dependent kinase 4 and cyclin D1 and upregulation of p21Cip1 in a dose‑dependent manner. Furthermore, paeonol dose‑dependently induced cell apoptosis, accompanied by an increase in the Bax/Bcl‑2 ratio, release of cytochrome c and further activation of caspases. Paeonol also dose‑dependently blocked the activation of the Wnt/β‑catenin signaling pathway by suppressing the expression of β‑catenin, resulting in a decrease in β‑catenin‑mediated activity of TCF/LEF and downregulation of downstream target genes, including cyclin D1, survivin and c‑Myc. Therefore, the present results suggested that paeonol exerted its anti‑tumor effects on CRC cells, including the inhibition of cell proliferation, induction of cell cycle arrest and initiation of apoptosis, at least partly by suppressing the Wnt/β‑catenin pathway, which may offer a promising therapeutic strategy for CRC.
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August-2020
Volume 46 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos
Liu L, Shi R and Chen Z: Paeonol exerts anti‑tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/β‑catenin signaling pathway. Int J Mol Med 46: 675-684, 2020
APA
Liu, L., Shi, R., & Chen, Z. (2020). Paeonol exerts anti‑tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/β‑catenin signaling pathway. International Journal of Molecular Medicine, 46, 675-684. https://doi.org/10.3892/ijmm.2020.4629
MLA
Liu, L., Shi, R., Chen, Z."Paeonol exerts anti‑tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/β‑catenin signaling pathway". International Journal of Molecular Medicine 46.2 (2020): 675-684.
Chicago
Liu, L., Shi, R., Chen, Z."Paeonol exerts anti‑tumor activity against colorectal cancer cells by inducing G0/G1 phase arrest and cell apoptosis via inhibiting the Wnt/β‑catenin signaling pathway". International Journal of Molecular Medicine 46, no. 2 (2020): 675-684. https://doi.org/10.3892/ijmm.2020.4629