Actein induces apoptosis in leukemia cells through suppressing RhoA/ROCK1 signaling pathway

  • Authors:
    • Wen-Di Zhou
    • Xiang Wang
    • Xing-Zhen Sun
    • Jian Hu
    • Rong-Rong Zhang
    • Ze Hong
  • View Affiliations

  • Published online on: October 10, 2017     https://doi.org/10.3892/ijo.2017.4150
  • Pages:1831-1841
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Abstract

Actein is a tetracyclic triterpenoid compound, extracted from the rhizome of Cimicifuga foetida, exhibiting anticancer activities as previously reported. However, the effects of actein on human leukemia have not been explored before. In this study, the role of actein in regulating apoptosis induction in human leukemia cells was investigated. Actein administration significantly enhanced apoptosis, especially in human leukemia cell line of U937 and the primary human leukemia cells. The promotion was accompanied by caspase-9, caspase-3 and poly(ADP-ribose) polymerase (PARP) cleavage, and cytochrome c (Cyto-c) release. Additionally, translocation of Bax into mitochondria was increased by actein, while anti-apoptotic signals of myeloid cell leukemia-1 (Mcl-1) and B cell CLL/lymphoma 2 (Bcl-2) were decreased, accompanied by reduced phosphorylated Bcl-2-associated death promoter (Bad). Furthermore, protein kinase B (AKT) activation was downregulated by actein treatment in U937 cells. RhoA, but not caspase-3, regulated Rho kinase 1 (ROCK1) expression induced by actein. Suppression of RhoA and ROCK1 reduced ROCK1 expression, caspase-9, caspase-3 and PARP cleavage. In contrast, AKT inactivity enhanced apoptosis levels, as well as caspase signaling pathway expression. The anticancer role of actein was potentiated by inactivating AKT. In vivo, U937-bearing tumor growth was suppressed by actein, which was related to ROCK1 suppression, AKT dephosphorylation and apoptosis induction. These results indicated that actein has a suppressive role in human leukemia progression through inactivating RhoA/ROCK1 and inducing caspases.

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December 2017
Volume 51 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Zhou, W., Wang, X., Sun, X., Hu, J., Zhang, R., & Hong, Z. (2017). Actein induces apoptosis in leukemia cells through suppressing RhoA/ROCK1 signaling pathway. International Journal of Oncology, 51, 1831-1841. https://doi.org/10.3892/ijo.2017.4150
MLA
Zhou, W., Wang, X., Sun, X., Hu, J., Zhang, R., Hong, Z."Actein induces apoptosis in leukemia cells through suppressing RhoA/ROCK1 signaling pathway". International Journal of Oncology 51.6 (2017): 1831-1841.
Chicago
Zhou, W., Wang, X., Sun, X., Hu, J., Zhang, R., Hong, Z."Actein induces apoptosis in leukemia cells through suppressing RhoA/ROCK1 signaling pathway". International Journal of Oncology 51, no. 6 (2017): 1831-1841. https://doi.org/10.3892/ijo.2017.4150