Abstract
Current standard-of-care treatment for glioblastoma, the most common malignant primary central nervous system (CNS) tumor, consists of surgical resection followed by adjuvant chemotherapy and radiation (Stupp protocol), providing an overall median survival of 15 months. With additional treatment using tumor-treating fields (Optune® therapy, Novocure Ltd., Haifa, Israel), survival can be extended up to 20 months. In spite of significant progress in our understanding of the molecular pathogenesis, the prognosis for patients with malignant gliomas remains poor and additional treatment modalities are critically needed. Curcumin is a bright yellow pigment found in the rhizome of the widely utilized spice, turmeric (Curcuma longa). It has long been used in South Asian traditional medicines and has been demonstrated to have in vitro antioxidant, anti-inflammatory, and antiproliferative effects. Curcumin has been demonstrated to induce multiple cytotoxic effects in tumor cells including cell cycle arrest, apoptosis, autophagy, changes in gene expression, and disruption of molecular signaling. Additionally, curcumin has been shown to potentiate the effect of radiation on cancer cells, while exhibiting a protective effect on normal tissue. Curcumin’s positive safety profile and widespread availability make it a promising compound for future clinical trials for high-grade gliomas.
Highlights
Primary central nervous system (CNS) tumors represent a heterogeneous group of pathologies with variable prognosis, treatment, life expectancy, and molecular profiles
We aim to provide an updated review of the literature on the effects of curcumin in malignant gliomas focusing on experimental evidence from the last 5 years
The Wnt signaling pathway is an important part of adult tissue homeostasis and can induce mitogenic stimulation, cell fate specification, and differentiation via a signal cascade that begins on the surface of signal cells that bind to the Frizzled/low-density lipoprotein receptor-related protein complex at the target cell, resulting in signal transduction via Dishevelled, glycogen synthase kinase-3β, Axin, and adenomatous polyposis coli (APC), resulting in increased intracytoplasmic and intranuclear β-catenin concentration [26]
Summary
Primary central nervous system (CNS) tumors represent a heterogeneous group of pathologies with variable prognosis, treatment, life expectancy, and molecular profiles. CCuurrccuummiinn ((ddiiffeerruullooyymmeetthhaannee)) iiss aa yyeellllooww ppiiggmmeenntt ddeerriivveedd ffrroomm tthhee rrhhiizzoommee ooff ttuurrmmeerriicc ((CCuurrccuummaa lloonnggaa)) aanndd hhaass bbeeeenn uusseedd iinn ttrraaddiittiioonnaall IInnddiiaann AAyyuurrvveeddiicc aanndd SSoouutthheeaasstt AAssiiaann mmeeddiicciinnee ffoorr mmiilllleennnniiaa;; iitt hhaass ttrraaddiittiioonnaallllyy bbeeeenn kknnoowwnn ttoo hhaavvee aannttii--iinnflflaammmmaattoorryy eeffffeeccttss [[44]]. DDeemmeetthhooxxyyccuurrccuummiinn aanndd bbiiss--ddeemmeetthhooxxyyccuurrccuummiinn aarree tthhee mmaaiinn mmeettaabboolliitteess ooff ccuurrccuummiinn aanndd bbeelloonngg ttoo aa ccllaassss ooff cchheemmiiccaallss ccaalllleeddddiairayrlyhlhepetpatnaoniodisd[s5][.5I]n. KKeettoo--eennooll ttaauuttoommeerriissmm ooff ccuurrccuummiinn ddeeppeennddss oonn tthhee aacciiddiittyy ooff tthhee ssoolluuttiioonn,, wwiitthh eennooll ffoorrmm pprreeddoommiinnaattiinngg iinn aallkkaalliinnee mmeeddiiaa aanndd kkeettoo ffoorrmm pprreeddoommiinnaattiinngg iinn aacciiddiicc aanndd nneeuuttrraall mmeeddiiaa ((FFiigguurree 22)) [[55]]. Liposomes modified with MAN appear to preferentially target the cortex, cerebellum, brainstem, hippocampus, and pontine nuclei [19] Curcumin micelles are another form of increased bioavailability curcumin, approximately 19-fold greater than standard preparation curcumin [20]. Methods of increasing bioavailability as well as enhancing delivery to specific cellular targets will become increasingly important with translational studies
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