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Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells

  • Authors:
    • Thanet Sophonnithiprasert
    • Wilawan Mahabusarakam
    • Yukio Nakamura
    • Ramida Watanapokasin
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, Faculty of Medicine, Srinkharinwirot University, Bangkok 10110, Thailand, Department of Chemistry, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand, Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano 390‑8621, Japan
    Copyright: © Sophonnithiprasert et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 119-128
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    Published online on: November 11, 2016
       https://doi.org/10.3892/ol.2016.5381
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Abstract

Goniothalamin, a natural occurring styryl-lactone isolated from Goniothalamus macrophyllus (Blume) Hook. f. & Thomson var. macrophyllus, can trigger cancer cell death in various types of cancer cell. The present study focused on elucidation of the mitochondria‑mediated apoptosis associated with endoplasmic reticulum (ER) stress‑induced activation of c-Jun NH2-terminal kinase (JNK) by goniothalamin in HeLa cervical cancer cells. Cell viability was determined using an MTT assay, and DNA condensation and loss of mitochondrial membrane potential were determined using Hoechst 33342 and JC‑1 staining, respectively. Flow cytometry was used for cell cycle and phosphatidyl‑serine exposure analyses. Apoptotic‑associated ER stress signaling pathways were determined using immunoblotting, reverse transcription‑polymerase chain reaction (RT‑PCR) and RT‑quantitative PCR analyses. The results suggested that goniothalamin suppressed cell proliferation in a time‑ and dose‑dependent manner. The induction of apoptosis was confirmed by increased DNA condensation, loss of mitochondrial membrane potential and cell surface phosphatidyl‑serine presentation. The cell cycle analysis demonstrated that the goniothalamin‑treated HeLa cells were in G2/M arrest. Determination of the caspase cascade and apoptotic proteins indicated the induction of apoptosis through the intrinsic pathway. In addition, the levels of phosphorylated JNK and the transcription factor, C/EBP homologous protein (CHOP), an ER stress‑associated apoptotic molecule, were increased in the goniothalamin‑treated cells. These data indicated that goniothalamin exerted a cytotoxic effect against HeLa cells via the induction of mitochondria‑mediated apoptosis, associated with ER stress‑induced activation of JNK.
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Copy and paste a formatted citation
Spandidos Publications style
Sophonnithiprasert T, Mahabusarakam W, Nakamura Y and Watanapokasin R: Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells. Oncol Lett 13: 119-128, 2017.
APA
Sophonnithiprasert, T., Mahabusarakam, W., Nakamura, Y., & Watanapokasin, R. (2017). Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells. Oncology Letters, 13, 119-128. https://doi.org/10.3892/ol.2016.5381
MLA
Sophonnithiprasert, T., Mahabusarakam, W., Nakamura, Y., Watanapokasin, R."Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells". Oncology Letters 13.1 (2017): 119-128.
Chicago
Sophonnithiprasert, T., Mahabusarakam, W., Nakamura, Y., Watanapokasin, R."Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells". Oncology Letters 13, no. 1 (2017): 119-128. https://doi.org/10.3892/ol.2016.5381
Copy and paste a formatted citation
x
Spandidos Publications style
Sophonnithiprasert T, Mahabusarakam W, Nakamura Y and Watanapokasin R: Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells. Oncol Lett 13: 119-128, 2017.
APA
Sophonnithiprasert, T., Mahabusarakam, W., Nakamura, Y., & Watanapokasin, R. (2017). Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells. Oncology Letters, 13, 119-128. https://doi.org/10.3892/ol.2016.5381
MLA
Sophonnithiprasert, T., Mahabusarakam, W., Nakamura, Y., Watanapokasin, R."Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells". Oncology Letters 13.1 (2017): 119-128.
Chicago
Sophonnithiprasert, T., Mahabusarakam, W., Nakamura, Y., Watanapokasin, R."Goniothalamin induces mitochondria-mediated apoptosis associated with endoplasmic reticulum stress-induced activation of JNK in HeLa cells". Oncology Letters 13, no. 1 (2017): 119-128. https://doi.org/10.3892/ol.2016.5381
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