Abstract
Apoptosis and autophagy are the two prominent forms of developmental cell death, and researches have shown that crosstalk exists between these two processes. A prior study demonstrated that triptolide inhibited the proliferation of malignant glioma cells. However, whether apoptosis and autophagy participate in the inhibitory effect of triptolide in glioma cells has not been clarified. In the present study, we demonstrated that triptolide potently inhibited the growth of glioma cells by inducing cell cycle arrest at the G2/M phase. Additionally, the treatment with triptolide induced apoptosis and autophagy in various glioma cell lines. Triptolide-induced autophagy may have tumor-supporting effects. Autophagy and apoptosis could cross-inhibit each other in glioma cells treated with triptolide. Moreover, we found that triptolide induced ROS production and JNK activation and inhibited the activity of Akt and mTOR. Finally, we demonstrated that triptolide suppressed tumor growth in an orthotopic xenograft glioma model. Collectively, these data indicated that triptolide induced G2/M phase arrest, apoptosis, and autophagy via activating the ROS/JNK and blocking the Akt/mTOR signaling pathways in glioma cells. Triptolide may be a potential anti-tumor drug targeting gliomas.
Highlights
Gliomas are common and lethal malignant primary brain tumors with a poor prognosis that exhibit strong invasion, rapid progression, and vulnerability to relapse [1,2,3]
Triptolide induced morphological alterations in the glioma cells (Figure S1A) and dramatically inhibited colony formation (Figure 1D). These results suggest that compared to primary cultured astrocyte cells, the glioma cells were especially sensitive to the triptolide treatment
The cell cycle distribution analysis showed that treatment with a certain concentration of triptolide for 24 h increased the number of cells in the G2/M phase (Figure S1B and Figure 1E)
Summary
Gliomas are common and lethal malignant primary brain tumors with a poor prognosis that exhibit strong invasion, rapid progression, and vulnerability to relapse [1,2,3]. The treatment of gliomas has become multi-modality over the past few decades. The current standard of care for gliomas is surgery, followed by radiotherapy and the first-line chemotherapy agent temozolomide (TMZ). This treatment intervention has little impact on the survival rate of patients, during which the survival rate has only increased by 3–6 months [4]. It is urgent to explore alternative treatments to provide new hope for the treatment of gliomas.
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