Anticancer Mechanism of Curcumin on Human Glioblastoma

Abstract

Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin's anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.

Keywords: anticancer; curcumin; glioblastoma; molecular signaling mechanism.

Figure 1

Mode of curcumin actions as anti-cancer agent on the key molecular targets in GBM. Curcumin possesses anti-cancer properties by inhibiting signaling pathways and their downstream molecular targets; (a) retinoblastoma (RB) pathway; (b) p53 pathway; (c) JAK1,2/STAT3 pathway; (d) MAP kinase pathway; (e) P13K/Akt pathway; (f) Shh pathway; (g) NF-κB pathway. Molecular targets and signaling pathways that are upregulated and downregulated by curcumin are noted by using → and ┤, respectively.