Therapeutic Potential of Curcumin in the Treatment of Glioblastoma Multiforme

Author(s): Seyed Hossein Shahcheraghi, Mahtab Zangui, Marzieh Lotfi, Majid Ghayour-Mobarhan, Ahmad Ghorbani, Hossein Zarei Jaliani, Hamid Reza Sadeghnia, Amirhossein Sahebkar*.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 3 , 2019


Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite standard multimodality treatment, the highly aggressive nature of GBM makes it one of the deadliest human malignancies. The anti-cancer effects of dietary phytochemicals like curcumin provide new insights to cancer treatment. Evaluation of curcumin’s efficacy against different malignancies including glioblastoma has been a motivational research topic and widely studied during the recent decade. In this review, we discuss the recent observations on the potential therapeutic effects of curcumin against glioblastoma. Curcumin can target multiple signaling pathways involved in developing aggressive and drug-resistant features of glioblastoma, including pathways associated with glioma stem cell activity. Notably, combination therapy with curcumin and chemotherapeutics like temozolomide, the GBM standard therapy, as well as radiotherapy has shown synergistic response, highlighting curcumin’s chemo- and radio-sensitizing effect. There are also multiple reports for curcumin nanoformulations and targeted forms showing enhanced therapeutic efficacy and passage through blood-brain barrier, as compared with natural curcumin. Furthermore, in vivo studies have revealed significant anti-tumor effects, decreased tumor size and increased survival with no notable evidence of systemic toxicity in treated animals. Finally, a pharmacokinetic study in patients with GBM has shown a detectable intratumoral concentration, thereby suggesting a potential for curcumin to exert its therapeutic effects in the brain. Despite all the evidence in support of curcumin’s potential therapeutic efficacy in GBM, clinical reports are still scarce. More studies are needed to determine the effects of combination therapies with curcumin and importantly to investigate the potential for alleviating chemotherapy- and radiotherapy-induced adverse effects.

Keywords: Glioblastoma, curcumin, anti-cancer effects, phytochemicals, temozolomide, chemotherapy.

Ostrom QT, Bauchet L, Davis FG, et al. The epidemiology of glioma in adults: a “state of the science” review. Neuro-oncol 2014; 16(7): 896-913.
Venteicher AS, Tirosh I, Hebert C, et al. 142 Genetic and nongenetic determinants of cellular architecture in IDH1-mutant oligodendrogliomas and astrocytomas using single-cell transcriptome analysis. Neurosurgery 2016; 63: 158-8.
Di Costanzo A, Scarabino T, Trojsi F, et al. Recurrent glioblastoma multiforme versus radiation injury: a multiparametric 3-T MR approach. Radiol Med (Torino) 2014; 119(8): 616-24.
Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 2009; 10(5): 459-66.
Liu E, Wu J, Cao W, et al. Curcumin induces G2/M cell cycle arrest in a p53-dependent manner and upregulates ING4 expression in human glioma. J Neurooncol 2007; 85(3): 263-70.
Xie JC, Yang S, Liu XY, Zhao YX. Effect of marital status on survival in glioblastoma multiforme by demographics, education, economic factors, and insurance status. Cancer Med 2018; 7(8): 3722-42.
Spratt DE, Folkert M, Zumsteg ZS, et al. Temporal relationship of post-operative radiotherapy with temozolomide and oncologic outcome for glioblastoma. J Neurooncol 2014; 116(2): 357-63.
Goel A, Aggarwal BB. Curcumin, the golden spice from Indian saffron, is a chemosensitizer and radiosensitizer for tumors and chemoprotector and radioprotector for normal organs. Nutr Cancer 2010; 62(7): 919-30.
Meesarapee B, Thampithak A, Jaisin Y, et al. Curcumin I mediates neuroprotective effect through attenuation of quinoprotein formation, p-p38 MAPK expression, and caspase-3 activation in 6-hydroxydopamine treated SH-SY5Y cells. Phytother Res 2014; 28(4): 611-6.
Seo EJ, Fischer N, Efferth T. Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease. Pharmacol Res 2018; 129: 262-73.
Gersey ZC, Rodriguez GA, Barbarite E, et al. Curcumin decreases malignant characteristics of glioblastoma stem cells via induction of reactive oxygen species. BMC Cancer 2017; 17(1): 99.
Malzkorn B, Reifenberger G. Practical implications of integrated glioma classification according to the World Health Organization classification of tumors of the central nervous system 2016. Curr Opin Oncol 2016; 28(6): 494-501.
Smith C, Ironside JW. Diagnosis and pathogenesis of gliomas. Curr Diagn Pathol 2007; 13: 180-92.
Agnihotri S, Burrell KE, Wolf A, et al. Glioblastoma, a brief review of history, molecular genetics, animal models and novel therapeutic strategies. Arch Immunol Ther Exp (Warsz) 2013; 61(1): 25-41.
Eckel-Passow JE, Lachance DH, Molinaro AM, et al. Glioma groups based on 1p/19q, IDH, and TERT promoter mutations in tumors. N Engl J Med 2015; 372(26): 2499-508.
Hashiba T, Izumoto S, Kagawa N, et al. Expression of WT1 protein and correlation with cellular proliferation in glial tumors. Neurol Med Chir (Tokyo) 2007; 47(4): 165-70.
Ohgaki H, Kleihues P. The definition of primary and secondary glioblastoma. Clin Cancer Res 2013; 19(4): 764-72.
Liu Y, Yan W, Zhang W, et al. MiR-218 reverses high invasiveness of glioblastoma cells by targeting the oncogenic transcription factor LEF1. Oncol Rep 2012; 28(3): 1013-21.
Cloughesy TF, Cavenee WK, Mischel PS. Glioblastoma: from molecular pathology to targeted treatment. Annu Rev Pathol 2014; 9: 1-25.
Aldape K, Zadeh G, Mansouri S, Reifenberger G, von Deimling A. Glioblastoma: pathology, molecular mechanisms and markers. Acta Neuropathol 2015; 129(6): 829-48.
McLendon R, Friedman A, Bigner D, et al. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 2008; 455(7216): 1061-8.
Verhaak RG, Hoadley KA, Purdom E, et al. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 2010; 17(1): 98-110.
Appin CL, Brat DJ. Molecular genetics of gliomas. Cancer J 2014; 20(1): 66-72.
Witkin JM, Li X. Curcumin, an active constiuent of the ancient medicinal herb Curcuma longa L.: some uses and the establishment and biological basis of medical efficacy. CNS Neurol Disord Drug Targets 2013; 12: 487-97.
Sahebkar A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res 2014; 28(5): 633-42.
Panahi Y, Hosseini MS, Khalili N, Naimi E, Majeed M, Sahebkar A. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin Nutr 2015; 34(6): 1101-8.
Sahebkar A, Cicero AFG, Simental-Mendía LE, Aggarwal BB, Gupta SC. Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacol Res 2016; 107: 234-42.
Panahi Y, Saadat A, Beiraghdar F, Sahebkar A. Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother Res 2014; 28(10): 1461-7.
Panahi Y, Alishiri GH, Parvin S, Sahebkar A. Mitigation of Systemic Oxidative Stress by Curcuminoids in Osteoarthritis: Results of a Randomized Controlled Trial. J Diet Suppl 2016; 13(2): 209-20.
Panahi Y, Ghanei M, Hajhashemi A, Sahebkar A. Effects of Curcuminoids-Piperine Combination on Systemic Oxidative Stress, Clinical Symptoms and Quality of Life in Subjects with Chronic Pulmonary Complications Due to Sulfur Mustard: A Randomized Controlled Trial. J Diet Suppl 2016; 13(1): 93-105.
Sahebkar A, Serban MC, Ursoniu S, Banach M. Effect of curcuminoids on oxidative stress: A systematic review and meta-analysis of randomized controlled trials. J Funct Foods 2015; 18: 898-909.
Lelli D, Sahebkar A, Johnston TP, Pedone C. Curcumin use in pulmonary diseases: State of the art and future perspectives. Pharmacol Res 2017; 115: 133-48.
Momtazi AA, Shahabipour F, Khatibi S, Johnston TP, Pirro M, Sahebkar A. Curcumin as a MicroRNA regulator in cancer: A review. Rev Physiol Biochem Pharmacol 2016; 171: 1-38.
Iranshahi M, Sahebkar A, Takasaki M, Konoshima T, Tokuda H. Cancer chemopreventive activity of the prenylated coumarin, umbelliprenin, in vivo. Eur J Cancer Prev 2009; 18(5): 412-5.
Sahebkar A, Cicero AFG, Simental-Mendía LE, Aggarwal BB, Gupta SC. Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials. Pharmacol Res 2016; 107: 234-42.
Ghandadi M, Sahebkar A. Curcumin: An Effective Inhibitor of Interleukin-6. Curr Pharm Des 2017; 23(6): 921-31.
Abdollahi E, Momtazi AA, Johnston TP, Sahebkar A. Therapeutic effects of curcumin in inflammatory and immune-mediated diseases: A nature-made jack-of-all-trades? J Cell Physiol 2018; 233(2): 830-48.
Karimian MS, Pirro M, Majeed M, Sahebkar A. Curcumin as a natural regulator of monocyte chemoattractant protein-1. Cytokine Growth Factor Rev 2017; 33: 55-63.
Cicero AFG, Colletti A, Bajraktari G, et al. Lipid lowering nutraceuticals in clinical practice: position paper from an International Lipid Expert Panel. Arch Med Sci 2017; 13(5): 965-1005.
Panahi Y, Khalili N, Hosseini MS, Abbasinazari M, Sahebkar A. Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complement Ther Med 2014; 22(5): 851-7.
Sahebkar A. Curcuminoids for the management of hypertriglyceridaemia. Nat Rev Cardiol 2014; 11(2): 123.
Ganjali S, Blesso CN, Banach M, Pirro M, Majeed M, Sahebkar A. Effects of curcumin on HDL functionality. Pharmacol Res 2017; 119: 208-18.
Momtazi AA, Banach M, Pirro M, Katsiki N, Sahebkar A. Regulation of PCSK9 by nutraceuticals. Pharmacol Res 2017; 120: 157-69.
Panahi Y, Khalili N, Sahebi E, et al. Antioxidant effects of curcuminoids in patients with type 2 diabetes mellitus: a randomized controlled trial. Inflammopharmacology 2017; 25(1): 25-31.
Rahmani S, Asgary S, Askari G, et al. Treatment of Non-alcoholic Fatty Liver Disease with Curcumin: A Randomized Placebo-controlled Trial. Phytother Res 2016; 30(9): 1540-8.
Panahi Y, Kianpour P, Mohtashami R, Jafari R, Simental-Mendía LE, Sahebkar A. Curcumin Lowers Serum Lipids and Uric Acid in Subjects With Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial. J Cardiovasc Pharmacol 2016; 68(3): 223-9.
Panahi Y, Rahimnia AR, Sharafi M, Alishiri G, Saburi A, Sahebkar A. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. Phytother Res 2014; 28(11): 1625-31.
Panahi Y, Khalili N, Sahebi E, et al. Effects of Curcuminoids Plus Piperine on Glycemic, Hepatic and Inflammatory Biomarkers in Patients with Type 2 Diabetes Mellitus: A Randomized Double-Blind Placebo-Controlled Trial. Drug Res (Stuttg) 2018; 68(7): 403-9.
Sahebkar A, Henrotin Y. Analgesic efficacy and safety of curcuminoids in clinical practice: A systematic review and meta-analysis of randomized controlled trials. Pain Med 2016; 17(6): 1192-202.
Panahi Y, Badeli R, Karami GR, Sahebkar A. Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder. Phytother Res 2015; 29(1): 17-21.
Gupta SC, Prasad S, Kim JH, et al. Multitargeting by curcumin as revealed by molecular interaction studies. Nat Prod Rep 2011; 28(12): 1937-55.
Hamzehzadeh L, Atkin SL, Majeed M, Butler AE, Sahebkar A. The versatile role of curcumin in cancer prevention and treatment: A focus on PI3K/AKT pathway. J Cell Physiol 2018; 233(10): 6530-7.
Gupta SC, Patchva S, Aggarwal BB. Therapeutic roles of curcumin: lessons learned from clinical trials. AAPS J 2013; 15(1): 195-218.
Lao CD, Ruffin MT IV, Normolle D, et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med 2006; 6: 10.
Plummer SM, Holloway KA, Manson MM, et al. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene 1999; 18(44): 6013-20.
Surh YJ, Chun KS, Cha HH, et al. Molecular mechanisms underlying chemopreventive activities of anti-inflammatory phytochemicals: down-regulation of COX-2 and iNOS through suppression of NF-kappa B activation. Mutat Res 2001; 480-481: 243-68.
Kunnumakkara AB, Guha S, Krishnan S, Diagaradjane P, Gelovani J, Aggarwal BB. Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. Cancer Res 2007; 67(8): 3853-61.
Wang D, Veena MS, Stevenson K, et al. Liposome-encapsulated curcumin suppresses growth of head and neck squamous cell carcinoma in vitro and in xenografts through the inhibition of nuclear factor kappaB by an AKT-independent pathway. Clin Cancer Res 2008; 14(19): 6228-36.
Mackenzie GG, Queisser N, Wolfson ML, Fraga CG, Adamo AM, Oteiza PI. Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin’s lymphoma cells. Int J Cancer 2008; 123(1): 56-65.
Subramaniam D, Ponnurangam S, Ramamoorthy P, et al. Curcumin induces cell death in esophageal cancer cells through modulating Notch signaling. PLoS One 2012; 7(2)e30590
Gogada R, Amadori M, Zhang H, et al. Curcumin induces Apaf-1-dependent, p21-mediated caspase activation and apoptosis. Cell Cycle 2011; 10(23): 4128-37.
Chen L, Li WF, Wang HX, et al. Curcumin cytotoxicity is enhanced by PTEN disruption in colorectal cancer cells. World J Gastroenterol 2013; 19(40): 6814-24.
Aoki H, Takada Y, Kondo S, Sawaya R, Aggarwal BB, Kondo Y. Evidence that curcumin suppresses the growth of malignant gliomas in vitro and in vivo through induction of autophagy: role of Akt and extracellular signal-regulated kinase signaling pathways. Mol Pharmacol 2007; 72(1): 29-39.
Xu X, Qin J, Liu W. Curcumin inhibits the invasion of thyroid cancer cells via down-regulation of PI3K/Akt signaling pathway. Gene 2014; 546(2): 226-32.
Bandyopadhyay D. Farmer to pharmacist: curcumin as an anti-invasive and antimetastatic agent for the treatment of cancer. Front Chem 2014; 2: 113.
Li L, Ahmed B, Mehta K, Kurzrock R. Liposomal curcumin with and without oxaliplatin: effects on cell growth, apoptosis, and angiogenesis in colorectal cancer. Mol Cancer Ther 2007; 6(4): 1276-82.
Lin YG, Kunnumakkara AB, Nair A, et al. Curcumin inhibits tumor growth and angiogenesis in ovarian carcinoma by targeting the nuclear factor-kappaB pathway. Clin Cancer Res 2007; 13(11): 3423-30.
Yamauchi Y, Izumi Y, Yamamoto J, Nomori H. Coadministration of erlotinib and curcumin augmentatively reduces cell viability in lung cancer cells. Phytother Res 2014; 28(5): 728-35.
Patel BB, Sengupta R, Qazi S, et al. Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF-1R. Int J Cancer 2008; 122(2): 267-73.
Shpitz B, Giladi N, Sagiv E, et al. Celecoxib and curcumin additively inhibit the growth of colorectal cancer in a rat model. Digestion 2006; 74(3-4): 140-4.
Yin H, Zhou Y, Wen C, et al. Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling. Oncol Rep 2014; 32(4): 1610-6.
Sung B, Kunnumakkara AB, Sethi G, Anand P, Guha S, Aggarwal BB. Curcumin circumvents chemoresistance in vitro and potentiates the effect of thalidomide and bortezomib against human multiple myeloma in nude mice model. Mol Cancer Ther 2009; 8(4): 959-70.
Ruiz de Porras V, Bystrup S, Martínez-Cardús A, et al. Curcumin mediates oxaliplatin-acquired resistance reversion in colorectal cancer cell lines through modulation of CXC-Chemokine/NF-κB signalling pathway. Sci Rep 2016; 6: 24675.
Roy S, Yu Y, Padhye SB, Sarkar FH, Majumdar APN. Difluorinated-curcumin (CDF) restores PTEN expression in colon cancer cells by down-regulating miR-21. PLoS One 2013; 8(7)e68543
Kim DH, Suh J, Surh YJ, Na HK. Regulation of the tumor suppressor PTEN by natural anticancer compounds. Ann N Y Acad Sci 2017; 1401(1): 136-49.
McCubrey JA, Lertpiriyapong K, Steelman LS, et al. Regulation of GSK-3 activity by curcumin, berberine and resveratrol: Potential effects on multiple diseases. Adv Biol Regul 2017; 65: 77-88.
Wang YT, Liu HS, Su CL. Curcumin-enhanced chemosensitivity of FDA-approved platinum (II)-based anti-cancer drugs involves downregulation of nuclear endonuclease G and NF-κB as well as induction of apoptosis and G2/M arrest. Int J Food Sci Nutr 2014; 65(3): 368-74.
Montopoli M, Ragazzi E, Froldi G, Caparrotta L. Cell-cycle inhibition and apoptosis induced by curcumin and cisplatin or oxaliplatin in human ovarian carcinoma cells. Cell Prolif 2009; 42(2): 195-206.
Panda AK, Chakraborty D, Sarkar I, Khan T, Sa G. New insights into therapeutic activity and anticancer properties of curcumin. J Exp Pharmacol 2017; 9: 31-45.
Norris L, Karmokar A, Howells L, Steward WP, Gescher A, Brown K. The role of cancer stem cells in the anti-carcinogenicity of curcumin. Mol Nutr Food Res 2013; 57(9): 1630-7.
Yu Y, Kanwar SS, Patel BB, Nautiyal J, Sarkar FH, Majumdar APN. Elimination of colon cancer stem-like cells by the combination of curcumin and FOLFOX. Transl Oncol 2009; 2(4): 321-8.
Scarpa ES, Ninfali P. Phytochemicals as Innovative Therapeutic Tools against Cancer Stem Cells. Int J Mol Sci 2015; 16(7): 15727-42.
Hong M, Tan HY, Li S, et al. Cancer Stem Cells: The Potential Targets of Chinese Medicines and Their Active Compounds. Int J Mol Sci 2016; 17(6): 17.
Shakeri A, Cicero AFG, Panahi Y, Mohajeri M, Sahebkar A. Curcumin: A naturally occurring autophagy modulator. J Cell Physiol 2018.
Perry MC, Demeule M, Régina A, Moumdjian R, Béliveau R. Curcumin inhibits tumor growth and angiogenesis in glioblastoma xenografts. Mol Nutr Food Res 2010; 54(8): 1192-201.
Zhuang W, Long L, Zheng B, et al. Curcumin promotes differentiation of glioma-initiating cells by inducing autophagy. Cancer Sci 2012; 103(4): 684-90.
Shi L, Fei X, Wang Z. Demethoxycurcumin was prior to temozolomide on inhibiting proliferation and induced apoptosis of glioblastoma stem cells. Tumour Biol 2015; 36(9): 7107-19.
Luthra PM, Lal N. Prospective of curcumin, a pleiotropic signalling molecule from Curcuma longa in the treatment of Glioblastoma. Eur J Med Chem 2016; 109: 23-35.
Dhandapani KM, Mahesh VB, Brann DW. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. J Neurochem 2007; 102(2): 522-38.
Howells LM, Mitra A, Manson MM. Comparison of oxaliplatin- and curcumin-mediated antiproliferative effects in colorectal cell lines. Int J Cancer 2007; 121(1): 175-83.
Howells LM, Sale S, Sriramareddy SN, et al. Curcumin ameliorates oxaliplatin-induced chemoresistance in HCT116 colorectal cancer cells in vitro and in vivo. Int J Cancer 2011; 129(2): 476-86.
Choi BH, Kim CG, Bae Y-S, Lim Y, Lee YH, Shin SY. p21 Waf1/Cip1 expression by curcumin in U-87MG human glioma cells: role of early growth response-1 expression. Cancer Res 2008; 68(5): 1369-77.
Ricciuti B, Foglietta J, Chiari R, et al. Emerging enzymatic targets controlling angiogenesis in cancer: preclinical evidence and potential clinical applications. Med Oncol 2017; 35(1): 4.
Ricciuti B, Foglietta J, Bianconi V, Sahebkar A, Pirro M. Enzymes involved in tumor-driven angiogenesis: A valuable target for anticancer therapy Semin Cancer Biol 2017; S1044-579X(17)30043-3.
Mercapide J, Lopez De Cicco R, Castresana JS, Klein-Szanto AJ. Stromelysin-1/matrix metalloproteinase-3 (MMP-3) expression accounts for invasive properties of human astrocytoma cell lines. Int J Cancer 2003; 106(5): 676-82.
Abdullah Thani NA, Sallis B, Nuttall R, et al. Induction of apoptosis and reduction of MMP gene expression in the U373 cell line by polyphenolics in Aronia melanocarpa and by curcumin. Oncol Rep 2012; 28(4): 1435-42.
Kim S-Y, Jung S-H, Kim H-S. Curcumin is a potent broad spectrum inhibitor of matrix metalloproteinase gene expression in human astroglioma cells. Biochem Biophys Res Commun 2005; 337(2): 510-6.
Perry MC, Demeule M, Régina A, Moumdjian R, Béliveau R. Curcumin inhibits tumor growth and angiogenesis in glioblastoma xenografts. Mol Nutr Food Res 2010; 54(8): 1192-201.
Rodriguez GA, Shah AH, Gersey ZC, et al. Investigating the therapeutic role and molecular biology of curcumin as a treatment for glioblastoma. Ther Adv Med Oncol 2016; 8(4): 248-60.
Huang T-Y, Tsai T-H, Hsu C-W, Hsu Y-C. Curcuminoids suppress the growth and induce apoptosis through caspase-3-dependent pathways in glioblastoma multiforme (GBM) 8401 cells. J Agric Food Chem 2010; 58(19): 10639-45.
Zanotto-Filho A, Braganhol E, Edelweiss MI, et al. The curry spice curcumin selectively inhibits cancer cells growth in vitro and in preclinical model of glioblastoma. J Nutr Biochem 2012; 23(6): 591-601.
Karmakar S, Banik NL, Patel SJ, Ray SK. Curcumin activated both receptor-mediated and mitochondria-mediated proteolytic pathways for apoptosis in human glioblastoma T98G cells. Neurosci Lett 2006; 407(1): 53-8.
Daido S, Yamamoto A, Fujiwara K, Sawaya R, Kondo S, Kondo Y. Inhibition of the DNA-dependent protein kinase catalytic subunit radiosensitizes malignant glioma cells by inducing autophagy. Cancer Res 2005; 65(10): 4368-75.
Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y, Kondo S. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ 2004; 11(4): 448-57.
Gozuacik D, Kimchi A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene 2004; 23(16): 2891-906.
Kanzawa T, Germano IM, Komata T, Ito H, Kondo Y, Kondo S. Role of autophagy in temozolomide-induced cytotoxicity for malignant glioma cells. Cell Death Differ 2004; 11(4): 448-57.
Zanotto-Filho A, Braganhol E, Klafke K, et al. Autophagy inhibition improves the efficacy of curcumin/temozolomide combination therapy in glioblastomas. Cancer Lett 2015; 358(2): 220-31.
Zhang H, Zhu Y, Sun X, et al. Curcumin-Loaded Layered Double Hydroxide Nanoparticles-Induced Autophagy for Reducing Glioma Cell Migration and Invasion. J Biomed Nanotechnol 2016; 12(11): 2051-62.
Su CC, Wang MJ, Chiu TL. The anti-cancer efficacy of curcumin scrutinized through core signaling pathways in glioblastoma. Int J Mol Med 2010; 26(2): 217-24.
Feng X, Zhou Q, Liu C, Tao M-L. Drug screening study using glioma stem-like cells. Mol Med Rep 2012; 6(5): 1117-20.
Shehzad A, Wahid F, Lee YS. Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials. Arch Pharm (Weinheim) 2010; 343(9): 489-99.
Shehzad A, Lee YS. Molecular mechanisms of curcumin action: signal transduction. Biofactors 2013; 39(1): 27-36.
Clement V, Sanchez P, de Tribolet N, Radovanovic I, Ruiz i Altaba A. HEDGEHOG-GLI1 signaling regulates human glioma growth, cancer stem cell self-renewal, and tumorigenicity. Curr Biol 2007; 17(2): 165-72.
Katoh Y, Katoh M. Hedgehog target genes: mechanisms of carcinogenesis induced by aberrant hedgehog signaling activation. Curr Mol Med 2009; 9(7): 873-86.
Du WZ, Feng Y, Wang XF, et al. Curcumin suppresses malignant glioma cells growth and induces apoptosis by inhibition of SHH/GLI1 signaling pathway in vitro and vivo. CNS Neurosci Ther 2013; 19(12): 926-36.
Huang T-Y, Hsu C-W, Chang W-C, Wang M-Y, Wu J-F, Hsu Y-C. Demethoxycurcumin retards cell growth and induces apoptosis in human brain malignant glioma GBM 8401 cells. Evid-Based Complem Altern Med 2012. 2012
Krist B, Florczyk U, Pietraszek-Gremplewicz K, Józkowicz A, Dulak J. The Role of miR-378a in Metabolism, Angiogenesis, and Muscle Biology. Int J Endocrinol 2015; 2015281756
Li W, Yang W, Liu Y, et al. MicroRNA-378 enhances inhibitory effect of curcumin on glioblastoma. Oncotarget 2017; 8(43): 73938-46.
Zhang I, Cui Y, Amiri A, Ding Y, Campbell RE, Maysinger D. Pharmacological inhibition of lipid droplet formation enhances the effectiveness of curcumin in glioblastoma. Eur J Pharm Biopharm 2016; 100: 66-76.
Mukherjee S, Baidoo J, Fried A, et al. Curcumin changes the polarity of tumor-associated microglia and eliminates glioblastoma. Int J Cancer 2016; 139(12): 2838-49.
Zanotto-Filho A, Coradini K, Braganhol E, et al. Curcumin-loaded lipid-core nanocapsules as a strategy to improve pharmacological efficacy of curcumin in glioma treatment. Eur J Pharm Biopharm 2013; 83(2): 156-67.
Dützmann S, Schiborr C, Kocher A, et al. Intratumoral Concentrations and Effects of Orally Administered Micellar Curcuminoids in Glioblastoma Patients. Nutr Cancer 2016; 68(6): 943-8.
Guo G, Fu S, Zhou L, et al. Preparation of curcumin loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) nanofibers and their in vitro antitumor activity against Glioma 9L cells. Nanoscale 2011; 3(9): 3825-32.
Karavasili C, Panteris E, Vizirianakis IS, Koutsopoulos S, Fatouros DG. Chemotherapeutic Delivery from a Self-Assembling Peptide Nanofiber Hydrogel for the Management of Glioblastoma. Pharm Res 2018; 35(8): 166.
Lim KJ, Bisht S, Bar EE, Maitra A, Eberhart CG. A polymeric nanoparticle formulation of curcumin inhibits growth, clonogenicity and stem-like fraction in malignant brain tumors. Cancer Biol Ther 2011; 11(5): 464-73.
Tahmasebi Mirgani M, Isacchi B, Sadeghizadeh M, et al. Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells. Int J Nanomedicine 2014; 9: 403-17.
Sarisozen C, Dhokai S, Tsikudo EG, Luther E, Rachman IM, Torchilin VP. Nanomedicine based curcumin and doxorubicin combination treatment of glioblastoma with scFv-targeted micelles: In vitro evaluation on 2D and 3D tumor models. Eur J Pharm Biopharm 2016; 108: 54-67.
Jamali Z, Khoobi M, Hejazi SM, et al. Evaluation of Targeted Curcumin (CUR) loaded PLGA Nanoparticles for in vitro. Photodynamic Therapy on Human Glioblastoma Cell Line 2018.
Shinde RL, Devarajan PV. Docosahexaenoic acid-mediated, targeted and sustained brain delivery of curcumin microemulsion. Drug Deliv 2017; 24(1): 152-61.
Langone P, Debata PR, Inigo Jdel R, et al. Coupling to a glioblastoma-directed antibody potentiates antitumor activity of curcumin. Int J Cancer 2014; 135(3): 710-9.
da Fonseca CO, Schwartsmann G, Fischer J, et al. Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas. Surg Neurol 2008; 70(3): 259-66.
Madane RG, Mahajan HS. Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study. Drug Deliv 2016; 23(4): 1326-34.
Zhuang X, Xiang X, Grizzle W, et al. Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 2011; 19(10): 1769-79.
Mirzaei H, Shakeri A, Rashidi B, Jalili A, Banikazemi Z, Sahebkar A. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomed Pharmacother 2017; 85: 102-12.
Mukherjee S, Fried A, Hussaini R, et al. Phytosomal curcumin causes natural killer cell-dependent repolarization of glioblastoma (GBM) tumor-associated microglia/macrophages and elimination of GBM and GBM stem cells. J Exp Clin Cancer Res 2018; 37(1): 168.
Momtazi AA, Sahebkar A. Difluorinated Curcumin: A Promising Curcumin Analogue with Improved Anti-Tumor Activity and Pharmacokinetic Profile. Curr Pharm Des 2016; 22(28): 4386-97.

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Article Details

Year: 2019
Page: [333 - 342]
Pages: 10
DOI: 10.2174/1381612825666190313123704
Price: $58

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