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Article Open Access

PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells

  • Authors:
    • Nobuhisa Yoshikawa
    • Hiroaki Kajiyama
    • Kae Nakamura
    • Fumi Utsumi
    • Kaoru Niimi
    • Hiroko Mitsui
    • Ryuichiro Sekiya
    • Shiro Suzuki
    • Kiyosumi Shibata
    • David Callen
    • Fumitaka Kikkawa
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan, Centre for Personalized Cancer Medicine, Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia
    Copyright: © Yoshikawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2543-2552
    |
    Published online on: March 3, 2016
       https://doi.org/10.3892/or.2016.4653
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Abstract

There is an intensive need for the development of novel drugs for the treatment of epithelial ovarian cancer (EOC), the most lethal gynecologic malignancy due to the high recurrence rate. TP53 mutation is a common event in EOC, particularly in high-grade serous ovarian cancer, where it occurs in more than 90% of cases. Recently, PRIMA-1 and PRIMA‑1MET (p53 reactivation and induction of massive apoptosis and its methylated form) were shown to have an antitumor effect on several types of cancer. Despite that PRIMA-1MET is the first compound evaluated in clinical trials, the antitumor effects of PRIMA-1MET on EOC remain unclear. In this study, we investigated the therapeutic potential of PRIMA-1MET for the treatment of EOC cells. PRIMA-1MET treatment of EOC cell lines (n=13) resulted in rapid apoptosis at various concentrations (24 h IC50 2.6-20.1 µM). The apoptotic response was independent of the p53 status and chemo-sensitivity. PRIMA‑1MET treatment increased intracellular reactive oxygen species (ROS), and PRIMA-1MET-induced apoptosis was rescued by an ROS scavenger. Furthermore, RNA expression analysis revealed that the mechanism of action of PRIMA‑1MET may be due to inhibition of antioxidant enzymes, such as Prx3 and GPx-1. In conclusion, our results suggest that PRIMA-1MET represents a novel therapeutic strategy for the treatment of ovarian cancer irrespective of p53 status and chemo-sensitivity.
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Copy and paste a formatted citation
Spandidos Publications style
Yoshikawa N, Kajiyama H, Nakamura K, Utsumi F, Niimi K, Mitsui H, Sekiya R, Suzuki S, Shibata K, Callen D, Callen D, et al: PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells. Oncol Rep 35: 2543-2552, 2016.
APA
Yoshikawa, N., Kajiyama, H., Nakamura, K., Utsumi, F., Niimi, K., Mitsui, H. ... Kikkawa, F. (2016). PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells. Oncology Reports, 35, 2543-2552. https://doi.org/10.3892/or.2016.4653
MLA
Yoshikawa, N., Kajiyama, H., Nakamura, K., Utsumi, F., Niimi, K., Mitsui, H., Sekiya, R., Suzuki, S., Shibata, K., Callen, D., Kikkawa, F."PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells". Oncology Reports 35.5 (2016): 2543-2552.
Chicago
Yoshikawa, N., Kajiyama, H., Nakamura, K., Utsumi, F., Niimi, K., Mitsui, H., Sekiya, R., Suzuki, S., Shibata, K., Callen, D., Kikkawa, F."PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells". Oncology Reports 35, no. 5 (2016): 2543-2552. https://doi.org/10.3892/or.2016.4653
Copy and paste a formatted citation
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Spandidos Publications style
Yoshikawa N, Kajiyama H, Nakamura K, Utsumi F, Niimi K, Mitsui H, Sekiya R, Suzuki S, Shibata K, Callen D, Callen D, et al: PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells. Oncol Rep 35: 2543-2552, 2016.
APA
Yoshikawa, N., Kajiyama, H., Nakamura, K., Utsumi, F., Niimi, K., Mitsui, H. ... Kikkawa, F. (2016). PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells. Oncology Reports, 35, 2543-2552. https://doi.org/10.3892/or.2016.4653
MLA
Yoshikawa, N., Kajiyama, H., Nakamura, K., Utsumi, F., Niimi, K., Mitsui, H., Sekiya, R., Suzuki, S., Shibata, K., Callen, D., Kikkawa, F."PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells". Oncology Reports 35.5 (2016): 2543-2552.
Chicago
Yoshikawa, N., Kajiyama, H., Nakamura, K., Utsumi, F., Niimi, K., Mitsui, H., Sekiya, R., Suzuki, S., Shibata, K., Callen, D., Kikkawa, F."PRIMA-1MET induces apoptosis through accumulation of intracellular reactive oxygen species irrespective of p53 status and chemo-sensitivity in epithelial ovarian cancer cells". Oncology Reports 35, no. 5 (2016): 2543-2552. https://doi.org/10.3892/or.2016.4653
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