Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells

  • Authors:
    • Guo Chen
    • Ke Wang
    • Bing-Ya Yang
    • Bo Tang
    • Jian-Xiang Chen
    • Zi-Chun Hua
  • View Affiliations

  • Published online on: September 22, 2011     https://doi.org/10.3892/ijo.2011.1210
  • Pages: 139-147
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Abstract

Although arsenic trioxide (As2O3) has been successfully employed in treatment of patients with APL (acute promyelocytic leukemia), the sensitivity of solid tumor cells to this treatment was much lower than APL cells. The single agent of As2O3 was inefficient for treatment of hepatocellular carcinoma (HCC) in phase II trial demonstrating that new modalities of treatment with enhanced therapeutic effect are needed. In this study, we showed that oridonin, a diterpenoid isolated from traditional Chinese medicine Rabdosia rubescences, greatly potentiated apoptosis induced by As2O3 in hepatocellular carcinoma cells. The synergistic pro-apoptosis effect of combination of these two drugs led to increase in intracellular reactive oxygen species (ROS) level and N-acetyl-L-cysteine (NAC), a thiol-containing anti-oxidant, was able to completely block the effect. The combination treatment induced ROS-dependent decrease in mitochondrial membrane potential (MMP) decrease, and relocation of Bax and cytochrome C. Besides, oridonin dramatically increased the intracellular Ca2+ overload triggered by As2O3. Furthermore, the co-treatment of oridonin and As2O3 induced ROS-mediated down-regulation of Akt and XIAP, and inhibition of NF-κB activation. The two drug combination enhanced tumor suppression activity in murine HCC model compared with single agent treatment in vivo. These findings demonstrate that oridonin can sensitize hepatocellular carcinoma cells to As2O3 treatment and will facilitate the optimization of As2O3 therapy for HCC patients.

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January 2012
Volume 40 Issue 1

Print ISSN: 1019-6439
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Spandidos Publications style
Chen G, Wang K, Yang B, Tang B, Chen J and Hua Z: Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells. Int J Oncol 40: 139-147, 2012
APA
Chen, G., Wang, K., Yang, B., Tang, B., Chen, J., & Hua, Z. (2012). Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells. International Journal of Oncology, 40, 139-147. https://doi.org/10.3892/ijo.2011.1210
MLA
Chen, G., Wang, K., Yang, B., Tang, B., Chen, J., Hua, Z."Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells". International Journal of Oncology 40.1 (2012): 139-147.
Chicago
Chen, G., Wang, K., Yang, B., Tang, B., Chen, J., Hua, Z."Synergistic antitumor activity of oridonin and arsenic trioxide on hepatocellular carcinoma cells". International Journal of Oncology 40, no. 1 (2012): 139-147. https://doi.org/10.3892/ijo.2011.1210