Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USA.
Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA.
Int J Mol Sci. 2019 Jan 18;20(2):399. doi: 10.3390/ijms20020399.
Autophagy and the (PI3K-Akt/mTOR) signaling pathway play significant roles in glioblastoma multiforme (GBM) cell death and survival. Curcumin (Cur) has been reported to prevent several cancers, including GBM. However, the poor solubility and limited bioavailability of natural Cur limits its application in preventing GBM growth. Previously, we have shown the greater apoptotic and anti-carcinogenic effects of solid lipid Cur particles (SLCP) than natural Cur in cultured GBM cells. Here, we compared the autophagic responses on cultured U-87MG, GL261, F98, C6-glioma, and N2a cells after treatment with Cur or SLCP (25 µM for 24 h). Different autophagy, mitophagy, and chaperone-mediated autophagy (CMA) markers, along with the PI3K-AKkt/mTOR signaling pathway, and the number of autophagy vacuoles were investigated after treatment with Cur and or SLCP. We observed increased levels of autophagy and decreased levels of mitophagy markers, along with inhibition of the PI3K-Akt/mTOR pathway after treatments with Cur or SLCP. Cell survival markers were downregulated, and cell death markers were upregulated after these treatments. We found greater effects in the case of SCLP-treated cells in comparison to Cur. Given that fewer effects were observed on C-6 glioma and N2a cells. Our results suggest that SLCP could be a safe and effective means of therapeutically modulating autophagy in GBM cells.
自噬和（PI3K-Akt/mTOR）信号通路在多形性胶质母细胞瘤（GBM）细胞死亡和存活中起着重要作用。姜黄素（Cur）已被报道可预防多种癌症，包括 GBM。然而，天然 Cur 的溶解度差和生物利用度有限限制了其在预防 GBM 生长中的应用。此前，我们已经表明，与天然 Cur 相比，固体脂质姜黄素粒子（SLCP）在培养的 GBM 细胞中具有更大的促凋亡和抗癌作用。在这里，我们比较了用姜黄素或 SLCP（25 µM，24 h）处理后培养的 U-87MG、GL261、F98、C6 神经胶质瘤和 N2a 细胞的自噬反应。在用 Cur 或 SLCP 处理后，研究了不同的自噬、线粒体自噬和伴侣介导的自噬（CMA）标志物，以及 PI3K-Akt/mTOR 信号通路和自噬空泡的数量。我们观察到在用 Cur 或 SLCP 处理后，自噬水平升高，线粒体自噬标志物水平降低，同时 PI3K-Akt/mTOR 通路受到抑制。细胞存活标志物下调，细胞死亡标志物上调。与 Cur 相比，我们在 SLCP 处理的细胞中观察到更大的作用。鉴于在 C-6 神经胶质瘤和 N2a 细胞中观察到的作用较少。我们的结果表明，SLCP 可能是一种安全有效的治疗方法，可以调节 GBM 细胞中的自噬。
