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AT‑101 induces G1/G0 phase arrest via the β‑catenin/cyclin D1 signaling pathway in human esophageal cancer cells

  • Authors:
    • Fuchang Que
    • Lixia Dai
    • Dan Zhou
    • Qinghuan Lin
    • Xiaoyun Zeng
    • Le Yu
    • Yilei Li
    • Shuwen Liu

  • View Affiliations

  • Published online on: November 20, 2018     https://doi.org/10.3892/or.2018.6876
  • Pages: 1415-1423
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Abstract

AT‑101, an orally available and well‑tolerated natural pan‑Bcl‑2 family protein inhibitor, has been reported to be effective against a variety of cancers. However, the mechanisms whereby AT‑101 exhibits anticancer activity have not been fully elucidated. In this study, we demonstrated that AT‑101 reduced the cell viability of human esophageal cancer cells by inducing G1/G0 phase arrest and apoptosis. Apoptotic cell death occurred later than cell cycle arrest, as evidenced by an increase in the proportion of Annexin V‑positive cells and cleaved caspase‑3, ‑9 and PARP protein levels. AT‑101 markedly downregulated the protein levels of phospho‑retinoblastoma (Ser 780) and cyclin D1, whereas it elevated protein levels of p53 and p21Waf1/Cip1, contributing to the inhibition of cell cycle progression. Moreover, AT‑101 substantially reduced β‑catenin expression. XAV‑939, a small molecule that inhibits the Wnt/β‑catenin signaling pathway by facilitating β‑catenin degradation, lowered β‑catenin and cyclin D1 protein expression to an extent similar to AT‑101. XAV‑939 alone resulted in G1/G0 phase arrest and further induced cell cycle arrest in combination with AT‑101, suggesting that the β‑catenin/cyclin D1 signaling pathway mediated, at least in part, the cell cycle arrest induced by AT‑101. The present study may shed new light on the anticancer activity of AT‑101 in relation to cell cycle arrest as well as apoptosis in human esophageal cancer cells.
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February-2019
Volume 41 Issue 2

Print ISSN: 1021-335X
Online ISSN:1791-2431

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  • Impact Factor: 4.2
  • Ranked Oncology
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  • CiteScore: 8.4
  • CiteScore Rank: Q1: #68/366 Oncology
  • Source Normalized Impact per Paper (SNIP): 0.786
  • SCImago Journal Rank (SJR): 0.812
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Spandidos Publications style
Que F, Dai L, Zhou D, Lin Q, Zeng X, Yu L, Li Y and Liu S: AT‑101 induces G1/G0 phase arrest via the β‑catenin/cyclin D1 signaling pathway in human esophageal cancer cells. Oncol Rep 41: 1415-1423, 2019
APA
Que, F., Dai, L., Zhou, D., Lin, Q., Zeng, X., Yu, L. ... Liu, S. (2019). AT‑101 induces G1/G0 phase arrest via the β‑catenin/cyclin D1 signaling pathway in human esophageal cancer cells. Oncology Reports, 41, 1415-1423. https://doi.org/10.3892/or.2018.6876
MLA
Que, F., Dai, L., Zhou, D., Lin, Q., Zeng, X., Yu, L., Li, Y., Liu, S."AT‑101 induces G1/G0 phase arrest via the β‑catenin/cyclin D1 signaling pathway in human esophageal cancer cells". Oncology Reports 41.2 (2019): 1415-1423.
Chicago
Que, F., Dai, L., Zhou, D., Lin, Q., Zeng, X., Yu, L., Li, Y., Liu, S."AT‑101 induces G1/G0 phase arrest via the β‑catenin/cyclin D1 signaling pathway in human esophageal cancer cells". Oncology Reports 41, no. 2 (2019): 1415-1423. https://doi.org/10.3892/or.2018.6876