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Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells

  • Authors:
    • Kristina Shilnikova
    • Mei Jing Piao
    • Kyoung Ah Kang
    • Yea Seong Ryu
    • Jeong Eon Park
    • Yu Jae Hyun
    • Ao Xuan Zhen
    • Yong Joo Jeong
    • Uhee Jung
    • In Gyu Kim
    • Jin Won Hyun
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea, Department of Bio and Nanochemistry, Kookmin University, Seoul 02707, Republic of Korea, Radiation Biotechnology Research Division, Korea Atomic Energy Research Institute, Jeongeup, Jeollabuk 56212, Republic of Korea, Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon 34057, Republic of Korea
    Copyright: © Shilnikova et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 5417-5424
    |
    Published online on: February 15, 2018
       https://doi.org/10.3892/ol.2018.8065
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Abstract

Cisplatin-based chemotherapy often results in the development of chemoresistance when used to treat ovarian cancer, which is difficult to overcome. The present study investigated the cytotoxic and anti‑migratory effects of shikonin, a naphthoquinone compound, on cisplatin‑resistant human ovarian cancer A2780 cells (A2780‑CR). Shikonin had a potent dose‑dependent cytotoxic effect on A2780‑CR cells, with 9 µM shikonin treatment reducing A2780‑CR cell viability by 50%, validate using an MTT assay. Shikonin induced apoptosis, as evidenced by the increased number of apoptotic bodies, following staining with Hoechst 33342, and terminal deoxynucleotidyl cell transferase dUTP nick end labeling‑positive cells following treatment. Flow cytometry and fluorescent microscope imaging, following JC‑1 staining, revealed that shikonin increased mitochondrial membrane depolarization. Also it altered the levels of apoptosis-associated proteins, leading to diminished expression of B cell lymphoma‑2 (Bcl‑2), enhanced expression of Bcl‑associated X, and cleavage of caspase‑9 and ‑3, as revealed using western blot analysis. Shikonin activated mitogen‑activated protein kinases; while treatment with specific inhibitors of these kinases attenuated the decline in cell viability induced by shikonin treatment. In addition, the cell migration assay and western blot analysis indicated that shikonin decreased the migratory capacity of A2780‑CR cells via the upregulation of epithelial‑cadherin and downregulation of neural‑cadherin. Taken together, the results of the present study indicated that shikonin induces mitochondria‑mediated apoptosis and attenuates the epithelial‑mesenchymal transition in A2780-CR cells.
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Copy and paste a formatted citation
Spandidos Publications style
Shilnikova K, Piao MJ, Kang KA, Ryu YS, Park JE, Hyun YJ, Zhen AX, Jeong YJ, Jung U, Kim IG, Kim IG, et al: Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells. Oncol Lett 15: 5417-5424, 2018.
APA
Shilnikova, K., Piao, M.J., Kang, K.A., Ryu, Y.S., Park, J.E., Hyun, Y.J. ... Hyun, J.W. (2018). Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells. Oncology Letters, 15, 5417-5424. https://doi.org/10.3892/ol.2018.8065
MLA
Shilnikova, K., Piao, M. J., Kang, K. A., Ryu, Y. S., Park, J. E., Hyun, Y. J., Zhen, A. X., Jeong, Y. J., Jung, U., Kim, I. G., Hyun, J. W."Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells". Oncology Letters 15.4 (2018): 5417-5424.
Chicago
Shilnikova, K., Piao, M. J., Kang, K. A., Ryu, Y. S., Park, J. E., Hyun, Y. J., Zhen, A. X., Jeong, Y. J., Jung, U., Kim, I. G., Hyun, J. W."Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells". Oncology Letters 15, no. 4 (2018): 5417-5424. https://doi.org/10.3892/ol.2018.8065
Copy and paste a formatted citation
x
Spandidos Publications style
Shilnikova K, Piao MJ, Kang KA, Ryu YS, Park JE, Hyun YJ, Zhen AX, Jeong YJ, Jung U, Kim IG, Kim IG, et al: Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells. Oncol Lett 15: 5417-5424, 2018.
APA
Shilnikova, K., Piao, M.J., Kang, K.A., Ryu, Y.S., Park, J.E., Hyun, Y.J. ... Hyun, J.W. (2018). Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells. Oncology Letters, 15, 5417-5424. https://doi.org/10.3892/ol.2018.8065
MLA
Shilnikova, K., Piao, M. J., Kang, K. A., Ryu, Y. S., Park, J. E., Hyun, Y. J., Zhen, A. X., Jeong, Y. J., Jung, U., Kim, I. G., Hyun, J. W."Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells". Oncology Letters 15.4 (2018): 5417-5424.
Chicago
Shilnikova, K., Piao, M. J., Kang, K. A., Ryu, Y. S., Park, J. E., Hyun, Y. J., Zhen, A. X., Jeong, Y. J., Jung, U., Kim, I. G., Hyun, J. W."Shikonin induces mitochondria-mediated apoptosis and attenuates epithelial-mesenchymal transition in cisplatin-resistant human ovarian cancer cells". Oncology Letters 15, no. 4 (2018): 5417-5424. https://doi.org/10.3892/ol.2018.8065
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