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Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells

  • Authors:
    • Ning Kang
    • Shi-Jie Cao
    • Yan Zhou
    • Hao He
    • Shin-Ichi Tashiro
    • Satoshi Onodera
    • Feng Qiu
    • Takashi Ikejima
  • View Affiliations / Copyright

    Affiliations: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P.R. China, Department of Natural Products Chemistry, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China, China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China, Institute for Clinical and Biomedical Sciences, Kyoto 603-8072, Japan, Department of Clinical and Biomedical Science, Showa Pharmaceutical University, Tokyo 194-8543, Japan, College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, P.R. China
    Copyright: © Kang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2045-2056
    |
    Published online on: September 28, 2015
       https://doi.org/10.3892/ijo.2015.3186
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Abstract

Rabdosia rubescens, a commonly used traditional Chinese medicine, has increasingly gained attention for its use as an antitumor herb. Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, has been reported to induce apoptosis in human laryngeal cancer HEp-2 cells by our group. Here, we made unexpected observations that the caspase-9 inhibitor (C9i) enhanced apoptosis in response to selected stimuli, and HEp-2 cells which were made deficient in caspase-9 using siRNA exhibited no resistance to apoptotic signals and actually demonstrated increased apoptotic sensitivity to oridonin. The results were reversed by the transfection of an exogenous caspase-9 expression vector. Caspase-9 reduced sensitivity to apoptotic stimuli through reactive oxygen species (ROS)-suppressing and autophagy-promoting methods. ROS triggered the progression of apoptosis through activation of both the caspase-9-independent mitochondrial pathway and death receptor pathways, and the autophagy had an anti-apoptotic function in oridonin-treated HEp-2 cells. These collective results suggest that oridonin targets caspase-9 to alter ROS production and autophagy situation to promote HEp-2 cell apoptosis. Therefore, oridonin has the potential to be developed as an anticancer agent, and the combination of oridonin with those agents leading to reduction of caspase-9 expression in tumor cells could represent a novel approach to human laryngeal cancer treatment.
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Copy and paste a formatted citation
Spandidos Publications style
Kang N, Cao S, Zhou Y, He H, Tashiro S, Onodera S, Qiu F and Ikejima T: Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells. Int J Oncol 47: 2045-2056, 2015.
APA
Kang, N., Cao, S., Zhou, Y., He, H., Tashiro, S., Onodera, S. ... Ikejima, T. (2015). Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells. International Journal of Oncology, 47, 2045-2056. https://doi.org/10.3892/ijo.2015.3186
MLA
Kang, N., Cao, S., Zhou, Y., He, H., Tashiro, S., Onodera, S., Qiu, F., Ikejima, T."Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells". International Journal of Oncology 47.6 (2015): 2045-2056.
Chicago
Kang, N., Cao, S., Zhou, Y., He, H., Tashiro, S., Onodera, S., Qiu, F., Ikejima, T."Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells". International Journal of Oncology 47, no. 6 (2015): 2045-2056. https://doi.org/10.3892/ijo.2015.3186
Copy and paste a formatted citation
x
Spandidos Publications style
Kang N, Cao S, Zhou Y, He H, Tashiro S, Onodera S, Qiu F and Ikejima T: Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells. Int J Oncol 47: 2045-2056, 2015.
APA
Kang, N., Cao, S., Zhou, Y., He, H., Tashiro, S., Onodera, S. ... Ikejima, T. (2015). Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells. International Journal of Oncology, 47, 2045-2056. https://doi.org/10.3892/ijo.2015.3186
MLA
Kang, N., Cao, S., Zhou, Y., He, H., Tashiro, S., Onodera, S., Qiu, F., Ikejima, T."Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells". International Journal of Oncology 47.6 (2015): 2045-2056.
Chicago
Kang, N., Cao, S., Zhou, Y., He, H., Tashiro, S., Onodera, S., Qiu, F., Ikejima, T."Inhibition of caspase-9 by oridonin, a diterpenoid isolated from Rabdosia rubescens, augments apoptosis in human laryngeal cancer cells". International Journal of Oncology 47, no. 6 (2015): 2045-2056. https://doi.org/10.3892/ijo.2015.3186
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