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Article

Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling

  • Authors:
    • Qian Gong
    • Xiaozheng Cao
    • Jianguo Cao
    • Xiaohong Yang
    • Wenbin Zeng
  • View Affiliations / Copyright

    Affiliations: Pharmacy Department, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, P.R. China, School of Pharmaceutical Sciences, and Molecular Imaging Research Center, Central South University, Changsha, Hunan 410013, P.R. China, Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China, Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China, School of Pharmaceutical Sciences, and Molecular Imaging Research Center, Central South University, Changsha, Hunan 410013, P.R. China
  • Pages: 1401-1410
    |
    Published online on: July 5, 2018
       https://doi.org/10.3892/or.2018.6547
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Abstract

Casticin, a natural polymethoxyflavone isolated from A. annua, V. trifolia, and V. agnus‑castus induces apoptosis in cancer cells by activating FoxO3a. However, whether casticin inhibits in vitro carcinogenesis and cancer stem cell (CSC) characteristics, and whether casticin activates FoxO3a in small cell lung cancer (SCLC) cells remain unclear. We here demonstrated that casticin decreased sphere‑ and colony‑formation capabilities, and downregulated uPAR and CD133 in second‑generation spheres, which were considered as lung cancer stem‑like cells (LCSLCs), from SCLC H446 cells, in a concentration‑dependent manner. In addition, casticin dose‑dependently elevated the phosphorylation levels of AMPK and ACC, and reduced p‑FoxO3a expression. The above effects were attenuated by AMPK knockdown with small interfering RNAs (siRNAs). FoxO3a silencing resulted in decreased protein expression of FoxO3a, increased in vitro carcinogenesis and CSC characteristics, with no appreciable effects on AMPK and ACC phosphorylation, and displayed similar activities to those neutralizing the effects of casticin on in vitro carcinogenesis and CSC characteristics. These findings reveal a novel mechanism for regulating AMPK/FoxO3a signaling in response to casticin, suggesting a new strategy for SCLC therapy by targeting cancer stem‑like cells.
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Copy and paste a formatted citation
Spandidos Publications style
Gong Q, Cao X, Cao J, Yang X and Zeng W: Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling. Oncol Rep 40: 1401-1410, 2018.
APA
Gong, Q., Cao, X., Cao, J., Yang, X., & Zeng, W. (2018). Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling. Oncology Reports, 40, 1401-1410. https://doi.org/10.3892/or.2018.6547
MLA
Gong, Q., Cao, X., Cao, J., Yang, X., Zeng, W."Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling". Oncology Reports 40.3 (2018): 1401-1410.
Chicago
Gong, Q., Cao, X., Cao, J., Yang, X., Zeng, W."Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling". Oncology Reports 40, no. 3 (2018): 1401-1410. https://doi.org/10.3892/or.2018.6547
Copy and paste a formatted citation
x
Spandidos Publications style
Gong Q, Cao X, Cao J, Yang X and Zeng W: Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling. Oncol Rep 40: 1401-1410, 2018.
APA
Gong, Q., Cao, X., Cao, J., Yang, X., & Zeng, W. (2018). Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling. Oncology Reports, 40, 1401-1410. https://doi.org/10.3892/or.2018.6547
MLA
Gong, Q., Cao, X., Cao, J., Yang, X., Zeng, W."Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling". Oncology Reports 40.3 (2018): 1401-1410.
Chicago
Gong, Q., Cao, X., Cao, J., Yang, X., Zeng, W."Casticin suppresses the carcinogenesis of small cell lung cancer H446 cells through activation of AMPK/FoxO3a signaling". Oncology Reports 40, no. 3 (2018): 1401-1410. https://doi.org/10.3892/or.2018.6547
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