Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

Abstract

Brain malignancies currently carry a poor prognosis despite the current multimodal standard of care that includes surgical resection and adjuvant chemotherapy and radiation. As new therapies are desperately needed, naturally occurring chemical compounds have been studied for their potential chemotherapeutic benefits and low toxicity profile. Curcumin, found in the rhizome of turmeric, has extensive therapeutic promise via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown it to be an effective treatment for brain tumors including glioblastoma multiforme. These effects are potentiated by curcumin's ability to induce G2/M cell cycle arrest, activation of apoptotic pathways, induction of autophagy, disruption of molecular signaling, inhibition of invasion, and metastasis and by increasing the efficacy of existing chemotherapeutics. Further, clinical data suggest that it has low toxicity in humans even at large doses. Curcumin is a promising nutraceutical compound that should be evaluated in clinical trials for the treatment of human brain tumors.

Figure 1

(a) Curcuma longa from Koehler's Medicinal Plants, 1887. (b) From top to bottom, curcumin in its enol form, curcumin in its keto form, demethoxycurcumin, and bisdemethoxycurcumin.

Figure 2

Cancer pathway targets affected by curcumin. When the listed targets have multiple contributions to tumorigenesis (e.g., NF-κB), they are only placed under one category. Figure modified^∗ from Davis et al. 2003 [44]. ^∗As permitted by Creative Commons Attribution-NonCommercial-Share Alike 3.0 license and BJC OPEN initiative. ABCG2: ATP-binding cassette subfamily G member 2; AKT: protein kinase B; AP-1: activator protein 1; BAK: Bcl-2 homologous antagonist/killer; BAX: Bcl-2-like protein 4; Bcl-2: B-cell lymphoma 2; Bcl-xL: B-cell lymphoma-extra large; caspase: cysteine-aspartic protease; CD105: endoglin; CD31: platelet endothelial cell adhesion molecule (PECAM-1); CDC: cell division cycle; CDK: cyclin-dependent kinase; CDKI: cyclin-dependent kinase inhibitor; CHK1: checkpoint kinase 1; c-Myc: v-Myc avian myelocytomatosis viral oncogene homolog; COX-2: prostaglandin-endoperoxide synthase 2; CXCR-4: C-X-C chemokine receptor type 4; EGFR: epidermal growth factor receptor; EGR-1: early growth response protein 1; ERCC-1: excision repair cross-complementation group 1; ERK: extracellular signal-regulated kinases; FGF: fibroblast growth factor; GLI1: GLI family zinc finger 1; HDAC: histone deacetylases; HIF1A: hypoxia inducible factor 1, alpha subunit; hTERT: telomerase reverse transcriptase; ICAM-1: intercellular adhesion molecule 1; IL: interleukin; JAK: Janus kinase; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinases; MMP: matrix metalloproteinases; MRP: multidrug resistance protein; mTOR: mechanistic target of rapamycin; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; Nrf2: nuclear factor (erythroid-derived 2) like 2; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; PTCH1: patched 1; SAC: spindle assembly checkpoint; SHH: sonic hedgehog; Snail: zinc finger protein SNAI1; STAT-3: signal transducer and activator of transcription 3; TIMP: tissue inhibitors of metalloproteinases; TNF: tumor necrosis factor; uPA: urokinase; VEGF: vascular endothelial growth factor.