Smh-3 induces G2/M arrest and apoptosis through calcium‑mediated endoplasmic reticulum stress and mitochondrial signaling in human hepatocellular carcinoma Hep3B cells

  • Authors:
    • Chin-Yu Liu
    • Jai-Sing Yang
    • Shih-Ming Huang
    • Jo-Hua Chiang
    • Ming-Hua Chen
    • Li-Jiau Huang
    • Ho-Yu Ha
    • Shinji Fushiya
    • Sheng-Chu Kuo
  • View Affiliations

  • Published online on: December 5, 2012     https://doi.org/10.3892/or.2012.2166
  • Pages: 751-762
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Abstract

In the present study, we investigated the antitumor effects of Smh-3 on the viability, cell cycle and apoptotic cell death in human hepatocellular carcinoma Hep3B cells in vitro. We also investigated the molecular mechanisms involved in the effects of Smh-3 on human hepatoma Hep3B cells, including the effects on protein and mRNA levels which were determined by western blotting and DNA microarray methods, respectively. The results demonstrated that Smh-3 induced growth inhibition, cell morphological changes and induction of G2/M arrest and apoptosis in Hep3B cells. DNA microarray assay identified numerous differentially expressed genes related to angiogenesis, autophagy, calcium-mediated ER stress signaling, cell adhesion, cell cycle and mitosis, cell migration, cytoskeleton organization, DNA damage and repair, mitochondrial-mediated apoptosis and cell signaling pathways. Furthermore, Smh-3 inhibited CDK1 activity, mitochondrial membrane potential (ΔΨm) and increased the cytosolic Ca2+ release and caspase-4, caspase-9 and caspase-3 activities in Hep3B cells. Western blot analysis demonstrated that Smh-3 increased the protein levels of caspase-4 and GADD153 that may lead to ER stress and consequently apoptosis in Hep3B cells. Taken together, Smh-3 acts against human hepatocellular carcinoma Hep3B cells in vitro through G2/M phase arrest and induction of calcium-mediated ER stress and mitochondrial-dependent apoptotic signaling pathways.
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February 2013
Volume 29 Issue 2

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

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Spandidos Publications style
Liu C, Yang J, Huang S, Chiang J, Chen M, Huang L, Ha H, Fushiya S and Kuo S: Smh-3 induces G2/M arrest and apoptosis through calcium‑mediated endoplasmic reticulum stress and mitochondrial signaling in human hepatocellular carcinoma Hep3B cells. Oncol Rep 29: 751-762, 2013.
APA
Liu, C., Yang, J., Huang, S., Chiang, J., Chen, M., Huang, L. ... Kuo, S. (2013). Smh-3 induces G2/M arrest and apoptosis through calcium‑mediated endoplasmic reticulum stress and mitochondrial signaling in human hepatocellular carcinoma Hep3B cells. Oncology Reports, 29, 751-762. https://doi.org/10.3892/or.2012.2166
MLA
Liu, C., Yang, J., Huang, S., Chiang, J., Chen, M., Huang, L., Ha, H., Fushiya, S., Kuo, S."Smh-3 induces G2/M arrest and apoptosis through calcium‑mediated endoplasmic reticulum stress and mitochondrial signaling in human hepatocellular carcinoma Hep3B cells". Oncology Reports 29.2 (2013): 751-762.
Chicago
Liu, C., Yang, J., Huang, S., Chiang, J., Chen, M., Huang, L., Ha, H., Fushiya, S., Kuo, S."Smh-3 induces G2/M arrest and apoptosis through calcium‑mediated endoplasmic reticulum stress and mitochondrial signaling in human hepatocellular carcinoma Hep3B cells". Oncology Reports 29, no. 2 (2013): 751-762. https://doi.org/10.3892/or.2012.2166