Abstract
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.
Highlights
According to the World Health Organization (WHO), glioblastoma multiforme (GBM) is one of the deadliest and most aggressive brain cancers, affecting millions of people world-wide
Our results suggest that solid lipid Cur particles (SLCP) induced autophagy markers greater than natural Cur, as well as the inhibition of mitophagy and the significant disruption of the phosphatidylinositol 3-kinase (PI3K)-Akt/mammalian target for the rapamycin (mTOR) pathway in all three GBM cells, without significant effects on C6-glioma and N2a cells
Our findings are supported by Liang and colleagues, who found that over-expression of Beclin-1 in U-87MG cells enhanced the capacity for cellular autophagy and induced apoptosis, whereas silencing of Beclin-1 decreased autophagic capacity [36]
Summary
According to the World Health Organization (WHO), glioblastoma multiforme (GBM) is one of the deadliest and most aggressive brain cancers, affecting millions of people world-wide. Whereas among all primary brain tumors only 15% are GBM [1]. Radiotherapy, and chemotherapeutic advancement, the GBM growth and proliferation cannot be effectively controlled. The most potent chemotherapeutic drug use to treat GBM is temozolomide (Temodar, TMZ), but resistance to TMZ limits its effectiveness. Neuroinflammation increases after treatment of TMZ, making the development of alternative therapies critically important. In this context, several investigators have studied the anti-cancer and anti-inflammatory effects of curcumin (Cur) in human malignancies, including those found in various tissues, such as breast, prostate, colon, liver, and brain [3,4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
