The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects

Abstract

The present review focuses on the multi-faceted effects of curcumin on the neurobiology glioblastoma multiforme (GBM), with a special emphasis on autophagy (ATG)-dependent molecular pathways activated by such a natural polyphenol. This is consistent with the effects of curcumin in a variety of experimental models of neurodegeneration, where the molecular events partially overlap with GBM. In fact, curcumin broadly affects various signaling pathways, which are similarly affected in cell degeneration and cell differentiation. The antitumoral effects of curcumin include growth inhibition, cell cycle arrest, anti-migration and anti-invasion, as well as chemo- and radio-sensitizing activity. Remarkably, most of these effects rely on mammalian target of rapamycin (mTOR)-dependent ATG induction. In addition, curcumin targets undifferentiated and highly tumorigenic GBM cancer stem cells (GSCs). When rescuing ATG with curcumin, the tumorigenic feature of GSCs is suppressed, thus counteracting GBM establishment and growth. It is noteworthy that targeting GSCs may also help overcome therapeutic resistance and reduce tumor relapse, which may lead to a significant improvement of GBM prognosis. The present review focuses on the multi-faceted effects of curcumin on GBM neurobiology, which represents an extension to its neuroprotective efficacy.

Keywords: anti-cancer effects; autophagy; curcuma longa; glioblastoma stem-like cells; natural polyphenols; neuroprotection.

Figure 1

Curcumin modulates major glioblastoma multiforme (GBM)-associated signaling pathways. The cartoon summarizes the major effects of curcumin on GBM cells. In fact, curcumin was shown to broadly affect core-signaling pathways of GBM neurobiology. For instance, curcumin suppresses tumor growth by inhibiting tumor-promoting pathways (i.e., nuclear factor κB (NF-kB), phosphoinositide 3-kinases/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR), Janus kinase/signal transducers and activators of transcription (JAK/STAT3) and mitogen-activated protein kinase (MAPK) pathways), while up-regulating major tumor-suppressing (i.e., p53 and p21, and caspase).

Figure 2

Effects of curcumin on GBM cancer stem cells (GSCs). The cartoon summarizes the major effects of curcumin on GSCs. In particular, curcumin was shown to decrease malignant characteristics of GSCs by targeting core-signaling pathways such as PI3K/Akt/mTOR, JAK/STAT3, and MAPK pathways.