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.
Highlights
The combretastatins are a group of antimitotic agents isolated from the bark of the South African tree Combretum caffrum
We examined whether erianininduced apoptosis and autophagy involve Reactive oxygen species (ROS) generation and Jun N-terminal kinase (JNK) activation in OS cells
A natural product derived from D. chrysotoxum, has been associated with potent antitumor activity against human cancer cell lines tested with IC50o100 nM
Summary
The combretastatins are a group of antimitotic agents isolated from the bark of the South African tree Combretum caffrum. Many cytotoxic agents and/or microtubule-targeting agents inhibit tumor cell proliferation by causing cell cycle G0-, S-, or G2/M-phase arrest.[11,12,13] The G2 checkpoint prevents cells from entering mitosis when DNA is damaged and ensures the propagation of error-free copies of the genome to each daughter cell. ROS triggers apoptosis by causing various cellular stresses, including DNA damage and microtubule disruption mediated by various signal transducers.[21,22] Several apoptotic effectors are redox-sensitive, such as caspases, Bcl-2, and cytochrome c, and their functions are markedly regulated by cellular ROS.[23] Recent studies have showed that antioxidative agents abolished the formation of autophagosomes and the consequent degradation of proteins.[24] Starvation-induced autophagy, in turn, resulted in ROS production and DNA damage by targeting the poly (ADPribose) polymerase (PARP) signaling pathway.[25]
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