1. Academic Validation
  2. Raddeanin A, a natural triterpenoid saponin compound, exerts anticancer effect on human osteosarcoma via the ROS/JNK and NF-κB signal pathway

Raddeanin A, a natural triterpenoid saponin compound, exerts anticancer effect on human osteosarcoma via the ROS/JNK and NF-κB signal pathway

  • Toxicol Appl Pharmacol. 2018 Aug 15;353:87-101. doi: 10.1016/j.taap.2018.05.025.
Bo Ma 1 Jianwei Zhu 1 Ang Zhao 1 Jie Zhang 1 Yu Wang 1 Hang Zhang 1 Lifang Zhang 2 Qi Zhang 3
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, People's Republic of China.
  • 2 College of Pharmaceutical and Life Sciences, Jiujiang University, Jiujiang 332000, People's Republic of China.
  • 3 School of Pharmaceutical Sciences, Nanjing Tech University, Nanjing 210009, People's Republic of China. Electronic address: zhangqi@njtech.edu.cn.
Abstract

Osteosarcoma (OS) is the most frequent and high mortality primary bone tumor in the adolescent. And it is well-known for poor prognosis due to high incidence of metastasis. Raddeanin A (RA), an active component of Anemone raddeana Regel, showed potential anti-cancer activities. However, the anti-tumor effect and molecular mechanism(s) of RA on osteosarcoma are still unclear. The present research is the first in vitro and in vivo investigate systematically Anticancer of RA on human osteosarcoma. Our study demonstrated that RA induced mitochondria-dependent Apoptosis in osteosarcoma cell lines and markedly suppressed the metastasis of osteosarcoma cells in vitro. And, RA treatment markedly inhibits tumor growth in vivo. Further mechanism study demonstrated that RA caused a significant enhance Reactive Oxygen Species (ROS) level to stimulate phosphorylation of JNK. Moreover, RA led to decrease of p-IκBα level in the cytosol and reduction of p65 level in the nucleus, which was associated with the inhibition of NF-κB transcriptional activity. When NF-κB signaling was inhibited by siRNA targeting p65, a significant increase in cell Apoptosis activity was observed. In addition, non-toxic RA concentrations (0.25, 0.5 and 1 μM) inhibited the migration and invasion of OS by suppressing MMP-2/9 expression associated with NF-κB-dependent transcription in vitro. The silencing of p65 increased the sensitivity of the osteosarcoma cells to RA suppressed migration and invasion. These findings suggest RA induces Apoptosis and inhibits metastasis in OS cells, involved in provoking ROS/JNK and inhibiting NF-κB signaling pathways. Therefore, it may be a potential anti-metastatic and anti-proliferative therapeutic agent for human osteosarcoma.

Keywords

Human osteosarcoma; Migration; NF-κB; ROS/JNK; Raddeanin A.

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