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Article

Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells

  • Authors:
    • Takashi Kasukabe
    • Junko Okabe-Kado
    • Nobuo Kato
    • Yoshio Honma
    • Shunichi Kumakura
  • View Affiliations / Copyright

    Affiliations: Department of Medical Education and Research, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan, Research Institute for Clinical Oncology, Saitama Cancer Center, Saitama 362-0806, Japan, Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047, Japan, Cancer Center, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan
  • Pages: 841-848
    |
    Published online on: November 18, 2014
       https://doi.org/10.3892/ijo.2014.2760
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Abstract

Arsenic trioxide (ATO) is an approved treatment for acute promyelocytic leukemia (APL). It has also shown potential for treatment of multiple myeloma and various solid tumors including breast cancer. The requirement of high, toxic concentrations for the induction of apoptosis in non-APL and solid tumor cells is a major limitation for its use in other hematological malignancies and solid tumors. We have examined whether inducers of differentiation of leukemia cells can control the growth of solid tumor cells. In the present study, we found that cotylenin A, a plant growth regulator and a potent inducer of differentiation in myeloid leukemia cells, significantly potentiated both ATO-induced inhibition of cell growth in a liquid culture, and ATO-induced inhibition of anchorage-independent growth in a semi-solid culture in human breast cancer MCF-7 and MDA-MB-231 cells. ISIR-005 (a synthetic cotylenin A-derivative) was also able to enhance ATO-induced growth inhibition. The combined treatment with cotylenin A and ATO induced cleaved caspase-7 in MCF-7 cells at the concentrations which ATO alone scarcely induced and cotylenin A alone only weakly induced. Expression of survivin in MCF-7 cells was markedly decreased with the presence of both cotylenin A and ATO, although the expression of survivin was only slightly decreased by cotylenin A or ATO alone. The pretreatment with N-acetylcysteine significantly reduced the combination treatment-induced cell growth inhibition. These data suggest that induction of cleaved caspase-7, inhibition of survivin and oxidative responses are important events in the corporative inhibition in the growth of MCF-7 cells induced by both cotylenin A and ATO. Furthermore, we found that the combined treatment with cotylenin A and ATO also could be effective in suppressing the invasive capacity of MDA-MB‑231 cells determined with the impedance-based xCELLigence Real-Time Cell Analysis technology. These results suggest that cotylenin A is an attractive enhancer for the ATO-induced anticancer activities in human breast cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Kasukabe T, Okabe-Kado J, Kato N, Honma Y and Kumakura S: Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells. Int J Oncol 46: 841-848, 2015.
APA
Kasukabe, T., Okabe-Kado, J., Kato, N., Honma, Y., & Kumakura, S. (2015). Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells. International Journal of Oncology, 46, 841-848. https://doi.org/10.3892/ijo.2014.2760
MLA
Kasukabe, T., Okabe-Kado, J., Kato, N., Honma, Y., Kumakura, S."Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells". International Journal of Oncology 46.2 (2015): 841-848.
Chicago
Kasukabe, T., Okabe-Kado, J., Kato, N., Honma, Y., Kumakura, S."Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells". International Journal of Oncology 46, no. 2 (2015): 841-848. https://doi.org/10.3892/ijo.2014.2760
Copy and paste a formatted citation
x
Spandidos Publications style
Kasukabe T, Okabe-Kado J, Kato N, Honma Y and Kumakura S: Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells. Int J Oncol 46: 841-848, 2015.
APA
Kasukabe, T., Okabe-Kado, J., Kato, N., Honma, Y., & Kumakura, S. (2015). Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells. International Journal of Oncology, 46, 841-848. https://doi.org/10.3892/ijo.2014.2760
MLA
Kasukabe, T., Okabe-Kado, J., Kato, N., Honma, Y., Kumakura, S."Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells". International Journal of Oncology 46.2 (2015): 841-848.
Chicago
Kasukabe, T., Okabe-Kado, J., Kato, N., Honma, Y., Kumakura, S."Cotylenin A and arsenic trioxide cooperatively suppress cell proliferation and cell invasion activity in human breast cancer cells". International Journal of Oncology 46, no. 2 (2015): 841-848. https://doi.org/10.3892/ijo.2014.2760
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