Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo.

Abstract

Erianin, a natural product derived from Dendrobium chrysotoxum, has exhibited potential antitumor activity in various malignancies, including hepatocarcinoma, melanoma, and promyelocytic leukemia. Here we explored the effects of erianin on osteosarcoma (OS) in vitro and in vivo and further elucidated the underlying molecule mechanisms. In this study, we found that erianin potently suppressed cell viability in various OS cell lines. Treatment with erianin induced G2/M-phase arrest, apoptosis, and autophagy in OS cells. Further studies showed that erianin-induced apoptosis and autophagy was attributed to reactive oxygen species (ROS), as N-acetyl cysteine (NAC), an ROS scavenger, attenuated them. Moreover, we found that erianin induced activation of c-Jun N-terminal kinase (JNK) signal pathway, which was also blocked by NAC. Downregulation of JNK by its specific inhibitor SP600125 could attenuate apoptosis and autophagy induced by erianin. Finally, erianin in vivo markedly reduced the growth with little organ-related toxicity. In conclusion, erianin induced cell cycle G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human OS. In light of these results, erianin may be a promising agent for anticancer therapy against OS.

• Authors: H Wang, T Zhang, W Sun, Z Wang, D Zuo, Z Zhou, S Li, J Xu, F Yin, Y Hua, Z Cai
• Journal: Cell death & disease (Cell Death Dis) Vol. 7 Issue 6 Pg. e2247 (06 02 2016) ISSN: 2041-4889 [Electronic] England
• PMID: 27253411 (Publication Type: Journal Article)

Chemical References

• Bibenzyls
• Erianin
• Reactive Oxygen Species
• Phenol
• JNK Mitogen-Activated Protein Kinases

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Bibenzyls
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• JNK Mitogen-Activated Protein Kinases (metabolism)
• MAP Kinase Signaling System (drug effects)
• Mice, Inbred BALB C
• Mice, Nude
• Osteosarcoma (pathology)
• Phenol
• Reactive Oxygen Species (metabolism)
• Xenograft Model Antitumor Assays