Abstract
Glioma, the most common intracranial tumor, harbors great harm. Since the treatment for it has reached the bottleneck stage, the development of new drugs becomes a trend. Therefore, we focus on the effect of scutellarin (SCU) and its combination with C18H17NO6 (abbreviated as combination) on glioma and its possible mechanism in this study. Firstly, SCU and C18H17NO6 both suppressed the proliferation of U251 and LN229 cells in a dose-dependent manner, and C18H17NO6 augmented the inhibition effect of SCU on U251 and LN229 cells in vitro. Moreover, there was an interactive effect between them. Secondly, SCU and C18H17NO6 decreased U251 cells in G2 phase and LN229 cells in G2 and S phases but increased U251 cells in S phase, respectively. Meanwhile, the combination could further reduce U251 cells in G2 phase and LN229 cells in G2 and S phases. Thirdly, SCU and C18H17NO6 both induced the apoptosis of U251 and LN229. The combination further increased the apoptosis rate of both cells compared with the two drugs alone. Furthermore, SCU and C18H17NO6 both inhibited the lateral and vertical migration of both cells, which was further repressed by the combination. More importantly, the effect of SCU and the combination was better than positive control-temozolomide, and the toxicity was low. Additionally, SCU and C18H17NO6 could suppress the growth of glioma in vivo, and the effect of the combination was better. Finally, SCU and the combination upregulated the presenilin 1 (PSEN1) level but inactivated the phosphatidylinositol 3−kinase (PI3K)-protein kinase B (AKT) signaling in vitro and in vivo. Accordingly, we concluded that scutellarin and its combination with C18H17NO6 suppressed the proliferation/growth and migration and induced the apoptosis of glioma, in which the mechanism might be associated with the repression of PSEN1/PI3K-AKT signaling axis.
Highlights
Glioma is the most common intracranial tumor, accounting for 80% of all primary malignant central nervous system tumors [1,2,3], which harbors all the characteristics of malignant tumors, including proliferation, invasion, and metastasis
Since presenilin 1 (PSEN1) inhibited cell proliferation and induced apoptosis by suppressing phosphatidylinositol 3−kinase/protein kinase B (PI3K/AKT) signaling [26, 27], we further explored whether PI3K/AKT signaling was involved in the inhibitory effect on glioma by scutellarin and C18H17NO6
The mechanism might be associated with the upregulated PSEN1 repressing the activation of PI3K-AKT signaling
Summary
Glioma is the most common intracranial tumor, accounting for 80% of all primary malignant central nervous system tumors [1,2,3], which harbors all the characteristics of malignant tumors, including proliferation, invasion, and metastasis. It was reported that scutellarin, with a strong PKM2 activation effect, could serve as an anticancer drug to suppress cell growth in prostate cancer [10,11,12]. Scutellarin took effect through the following mechanisms: [1] to reduce cell viability and sensitize RSV- and 5-FU-triggered apoptosis by modulating the expression of p53 and Bcl2/Bax [7, 15]; [2] to induce cell death by participating in metabolism and regulating the factors related with cell cycle and transcription [16]. Scutellarin inhibited cell proliferation and the metastasis and invasion into the lung and liver by downregulating STAT3/ Girdin/Akt signaling [17, 18]. Scutellarin exerts anticancer effects through different mechanisms in various tumors, its role in gliomas is still poorly studied
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