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Article

Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines

  • Authors:
    • Yong-Tae Ahn
    • Ik Jae Shin
    • Jong-Myoung Kim
    • Youn Sook Kim
    • Chu Lee
    • Seong-A. Ju
    • Won G. An
  • View Affiliations / Copyright

    Affiliations: Department of Biomedical Science, Kyungdong University, Goseong-gun, Gangwon-do 219‑832, Republic of Korea, School of Korean Medicine, Pusan National University, Yangsan, Busan 626-870, Republic of Korea, Department of Marine Biomaterials and Aquaculture, Pukyong National University, Busan 608-737, Republic of Korea, School of Medicine, Pusan National University, Yangsan, Busan 626-870, Republic of Korea, Aquaculture Industry Division, National Fisheries Research and Development Institute, Gangneung, Gangwon-do 210-861, Republic of Korea, Biomedical Research Center, Ulsan University Hospital, College of Medicine, University of Ulsan, Ulsan 682‑714, Republic of Korea
  • Pages: 1383-1389
    |
    Published online on: August 26, 2013
       https://doi.org/10.3892/ol.2013.1547
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Abstract

The actin cytoskeleton is important in the maintenance of cellular homeostasis and in signal transduction pathways leading to cell growth and apoptotic cell death in eukaryotic cells. Disruption of actin dynamics is associated with morphological changes in cancer cells. Deletion of phosphatase and tensin homolog (PTEN), a tumor suppressor gene involved in the regulation of the cell cycle and apoptosis, leads to cytoskeleton disruption and double-strand breaks (DSBs). To study the mechanism(s) of actin disruption-mediated apoptosis and its potential application for anticancer therapy, PTEN-null PC3M prostate cancer cells were treated with latrunculin B (LB). LB induced destabilization of the actin microfilament and apoptosis in a dose‑dependent manner, as demonstrated by morphological changes and nuclear condensation in the PC3M cells. In addition, it resulted in an increase in the levels of γH2AX recruitment, implicating the induction of DNA damage, including DSBs. Induction of Bax, with little effect on Bcl-2 expression, indicated that actin disruption causes apoptosis through activation of Bax signaling in PC3M cells. Treatment with U20126, a mitogen‑activated protein kinase kinase (MEK) inhibitor, resulted in attenuated induction of DSBs and apoptosis through activation of protein kinase B (Akt), suggesting that LB-mediated actin dysfunction induces DSBs via the MEK/extracellular signal-regulated kinase (Erk) pathway in cells. Therefore, counteracting activation of phosphorylated Akt stemming from the inhibition of MEK/Erk resulted in attenuation of actin disruption-induced apoptotic events in the PC3M cells. The results of this study provide information not only for use in delineation of the molecular association between actin disruption and tumorigenesis, but also for the development of a strategy for actin-based anticancer chemotherapy against highly metastatic prostate cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Ahn Y, Shin IJ, Kim J, Kim YS, Lee C, Ju S and An WG: Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines. Oncol Lett 6: 1383-1389, 2013.
APA
Ahn, Y., Shin, I.J., Kim, J., Kim, Y.S., Lee, C., Ju, S., & An, W.G. (2013). Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines. Oncology Letters, 6, 1383-1389. https://doi.org/10.3892/ol.2013.1547
MLA
Ahn, Y., Shin, I. J., Kim, J., Kim, Y. S., Lee, C., Ju, S., An, W. G."Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines". Oncology Letters 6.5 (2013): 1383-1389.
Chicago
Ahn, Y., Shin, I. J., Kim, J., Kim, Y. S., Lee, C., Ju, S., An, W. G."Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines". Oncology Letters 6, no. 5 (2013): 1383-1389. https://doi.org/10.3892/ol.2013.1547
Copy and paste a formatted citation
x
Spandidos Publications style
Ahn Y, Shin IJ, Kim J, Kim YS, Lee C, Ju S and An WG: Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines. Oncol Lett 6: 1383-1389, 2013.
APA
Ahn, Y., Shin, I.J., Kim, J., Kim, Y.S., Lee, C., Ju, S., & An, W.G. (2013). Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines. Oncology Letters, 6, 1383-1389. https://doi.org/10.3892/ol.2013.1547
MLA
Ahn, Y., Shin, I. J., Kim, J., Kim, Y. S., Lee, C., Ju, S., An, W. G."Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines". Oncology Letters 6.5 (2013): 1383-1389.
Chicago
Ahn, Y., Shin, I. J., Kim, J., Kim, Y. S., Lee, C., Ju, S., An, W. G."Counteracting the activation of pAkt by inhibition of MEK/Erk inhibition reduces actin disruption-mediated apoptosis in PTEN-null PC3M prostate cancer cell lines". Oncology Letters 6, no. 5 (2013): 1383-1389. https://doi.org/10.3892/ol.2013.1547
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