Abstract
Glioblastoma multiforme (GBM: also called glioblastoma) often occurs in the frontal and temporal lobes of the brain and develops from the glial cells. It is the most devastating and biologically aggressive tumor with challenging treatment strategies, in fact, with limited treatment protocols usually surgery, radiation, and chemotherapy with temozolomide (TMZ). The complex pathology appears to occur due to cellular stress produced by intra-/extracellular stimuli. Furthermore, it has been observed that the stress-induced reactive oxygen/nitrogen species (ROS/RNS) generation increases during GBM progression. Actually, such reactive species distort the activity of the antioxidant system as well as intracellular [Ca2+]i signaling of the glioma cells. In addition, it can induce the posttranslational modifications of cellular proteins and thereby result in the initiation and progression of GBM. Thus, the therapeutic values of the intra-/extracellular agents to modulate the redox status of GBM cells are under investigation. Herein, we summarized the salient features of the GBM and the role of ROS/RNS system in its progression along with the currently known strategies for its treatment.
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References
Akhavan D, Cloughesy TF, Mischel PS (2010) mTOR signaling in glioblastoma: lessons learned from bench to bedside. Neuro-Oncology 12(8):882–889. https://doi.org/10.1093/neuonc/noq052
Arismendi-Morillo G, Castellano-RamÃrez A, Seyfried TN (2017) Ultrastructuralcharacterization of the mitochondria-associated membranes abnormalities in human astrocytomas: functional and therapeutic simplications. Ultrastruct Pathol 41:234–244. https://doi.org/10.1080/01913123.2017.1300618
Barciszewska AM, Giel-Pietraszuk M, Perrigue PM et al (2019) Total DNA methylation changes reflect random oxidative dna damage in gliomas. Cell 8(9):1065. https://doi.org/10.3390/cells8091065.
Batash R, Asna N, Schaffer P et al (2017) Glioblastoma multiforme, diagnosis and treatment; recent literature review. Curr Med Chem 24(27):3002–3009. https://doi.org/10.2174/0929867324666170516123206
Beyer S, Fleming J, Meng W et al (2017) The role of miRNAs in angiogenesis, invasion and metabolism and their therapeutic implications in gliomas. Cancers (Basel) 9(7):85. https://doi.org/10.3390/cancers9070085.
Catacuzzeno L, Franciolini F (2018) Role of KCa3.1 channels in modulating ca2+ oscillations during glioblastoma cell migration and invasion. Int J Mol Sci 19(10):2970. https://doi.org/10.3390/ijms19102970.
Chen PH, Shih CM, Chang WC et al (2014) MicroRNA-302b-inhibited E2F3 transcription factor is related to all transretinoic acid-induced glioma cell apoptosis. J Neurochem 131(6):731–742. https://doi.org/10.1111/jnc.12820.
Chien CH, Chuang JY, Yang ST et al (2019) Enrichment of superoxide dismutase 2 in glioblastoma confers to acquisition of temozolomide resistance that is associated with tumor-initiating cell subsets. J Biomed Sci 26(1):77. https://doi.org/10.1186/s12929-019-0565-2.
Cholia RP, Dhiman M, Kumar R et al (2018) Oxidative stress stimulates invasive potential in rat C6 and human U-87 MG glioblastoma cells via activation and cross-talk between PKM2, ENPP2 and APE1 enzymes. Metab Brain Dis 33(4):1307–1326. https://doi.org/10.1007/s11011-018-0233-3
Chou YC, Chang MY, Wang MJ et al (2015) PEITC induces apoptosis of human brain glioblastoma GBM8401 cells through the extrinsic- and intrinsic-signaling pathways. Neurochem Int 81:32–40. https://doi.org/10.1016/j.neuint.2015.01.001.
Cipak Gasparovic A, Zarkovic N, Zarkovic K et al (2017) Biomarkers of oxidative and nitro-oxidative stress: conventional and novel approaches. Br J Pharmacol 174(12):1771–1783. https://doi.org/10.1111/bph.13673
Cobbs CS, Whisenhunt TR, Wesemann DR et al (2003) Inactivation of wild-type p53 protein function by reactive oxygen and nitrogen species in malignant glioma cells. Cancer Res 63(24):8670–8673
Cordani M, Oppici E, Dando I et al (2016) Mutant p53 proteins counteract autophagic mechanism sensitizing cancer cells to mTOR inhibition. Mol Oncol 10(7):1008–1029. https://doi.org/10.1016/j.molonc.2016.04.001
Cui Q, Wang JQ, Assaraf YG et al (2018) Modulating ROS to overcome multidrug resistance in cancer. Drug Resist Updat 41:1–25. https://doi.org/10.1016/j.drup.2018.11.001
Das A, Banik NL, Ray SK (2007) Garlic compounds generate reactive oxygen species leading to activation of stress kinases and cysteine proteases for apoptosis in human glioblastoma T98G and U87MG cells. Cancer 110(5):1083–1095. https://doi.org/10.1002/cncr.22888
D’Souza LC, Mishra S, Chakraborty A et al (2020) Oxidative stress and cancer development: are noncoding RNAs the missing links? Antioxid Redox Signal. https://doi.org/10.1089/ars.2019.7987
Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285(21):1182–1186. https://doi.org/10.1056/NEJM197111182852108
Fukai T, Ushio-Fukai M (2020) Cross-talk between NADPH oxidase and mitochondria: role in ROS signaling and angiogenesis. Cell 9(8):E1849. https://doi.org/10.3390/cells9081849
Gilardini Montani MS, Cecere N, Granato M et al (2019) Mutant p53, stabilized by its interplay with HSP90, activates a positive feed-back loop between NRF2 and p62 that induces chemo-resistance to apigenin in pancreatic cancer cells. Cancers (Basel) 11(5) pii: E703. https://doi.org/10.3390/cancers11050703
Görlach A, Bertram K, Hudecova S et al (2015) Calcium and ROS: a mutual interplay. Redox Biol 6:260–271. https://doi.org/10.1016/j.redox.2015.08.010.
Gupta P, Jagavelu K, Mishra DP (2015) Inhibition of NADPH Oxidase-4 potentiates 2-deoxy-D-glucose-induced suppression of glycolysis, migration, and invasion in glioblastoma cells: role of the Akt/HIF1α/HK-2 signaling Axis. Antioxid Redox Signal 23(8):665–681. https://doi.org/10.1089/ars.2014.5973.
Hameister R, Kaur C, Dheen ST et al (2020) Reactive oxygen/nitrogenspecies (ROS/RNS) and oxidative stress in arthroplasty. J Biomed Mater Res B Appl Biomater 108(5):2073–2087. https://doi.org/10.1002/jbm.b.34546
Hayes J, Thygesen H, Gregory W et al (2016) A validated microRNA profile with predictive potential in glioblastoma patients treated with bevacizumab. Mol Oncol 10:1296–1304
He Y, Su J, Lan B et al (2019) Targeting off-target effects: endoplasmic reticulum stress and autophagy as effective strategies to enhance temozolomide treatment. Onco Targets Ther 12:1857–1865. https://doi.org/10.2147/OTT.S194770.
Huang Z, Shi J, Gao Y et al (2019) HMDD v3.0: a database for experimentally supported human microRNA–disease associations. Nucleic Acids Res 47:D1013–D1017. https://doi.org/10.1093/nar/gky1010
Jha P, Pia Patric IR, Shukla S et al (2014) Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation. Neuro-Oncology 16(12):1607–1617. https://doi.org/10.1093/neuonc/nou113
Kabiraj P, Valenzuela CA, Marin JE et al (2015) The neuroprotective role of ferrostatin-1 under rotenone-induced oxidative stress in dopaminergic neuroblastoma cells. Protein J 34(5):349–358. https://doi.org/10.1007/s10930-015-9629-7
Kaminskyy VO, Zhivotovsky B (2014) Free radicals in cross talk between autophagy and apoptosis. Antioxid Redox Signal 21(1):86–102. https://doi.org/10.1089/ars.2013.5746.
Koundouros N, Poulogiannis G (2018) Phosphoinositide 3-kinase/Akt signaling and redox metabolism in cancer. Front Oncol 8:160. https://doi.org/10.3389/fonc.2018.00160.
Kruk J, Aboul-Enein HY (2017) Reactive oxygen and nitrogen species in carcinogenesis: implications of oxidative stress on the progression and development of several cancer types. Mini Rev Med Chem 17(11):904–919. https://doi.org/10.2174/1389557517666170228115324.
Kumari S, Badana AK, Murali Mohan G et al (2018) Reactive oxygen species: a key constituent in cancer survival. Biomark Insights 13. https://doi.org/10.1177/1177271918755391.
Li Y, Han N, Yin T et al (2014) Lentivirus-mediated Nox4 shRNA invasion and angiogenesis and enhances radiosensitivity in human glioblastoma. Oxidative Med Cell Longev 2014:581732. https://doi.org/10.1155/2014/581732
Lin Y, Jiang M, Chen W et al (2019) Cancer and ER stress: mutual crosstalk between autophagy, oxidative stress and inflammatory response. Biomed Pharmacother 118:109249. https://doi.org/10.1016/j.biopha.2019.109249.
Liu AJ, Wang SH, Chen KC et al (2013) Evodiamine, a plant alkaloid, induces calcium/JNK-mediated autophagy and calcium/mitochondria-mediated apoptosis in human glioblastoma cells [published correction appears in Chem Biol Interact (2017) 25;268:150]. Chem Biol Interact 205(1):20–28. https://doi.org/10.1016/j.cbi.2013.06.004
Liu Q, Zou R, Zhou R et al (2015) miR-155 regulates glioma cells invasion and chemosensitivity by p38 isoforms in vitro. J Cell Biochem 116(7):1213–1221. https://doi.org/10.1002/jcb.25073
Lo Dico A, Salvatore D, Martelli C et al (2019) Intracellular redox-balance involvement in temozolomide resistance-related molecular mechanisms in glioblastoma. Cell 8:11). pii: E1315. https://doi.org/10.3390/cells8111315
Lubanska D, Porter L (2017) Revisiting CDK inhibitors for treatment of glioblastoma multiforme. Drugs R D 17(2):255–263. https://doi.org/10.1007/s40268-017-0180-1
Luo JW, Wang X, Yang Y et al (2015) Role of micro-RNA (miRNA) in pathogenesis of glioblastoma. Eur Rev Med Pharmacol Sci 19(9):1630–1639
Massi P, Vaccani A, Ceruti S et al (2004) Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. J Pharmacol Exp Ther 308(3):838–845
More JY, Bruna BA, Lobos PE et al (2018) Calcium release mediated by redox-sensitive ryr2 channels has a central role in hippocampal structural plasticity and spatial memory. Antioxid Redox Signal 29(12):1125–1146. https://doi.org/10.1089/ars.2017.7277
Nà ger M, Sallán MC, Visa A et al (2018) Inhibition of WNT-CTNNB1 signaling upregulates SQSTM1 and sensitizes glioblastoma cells to autophagy blockers. Autophagy 14(4):619–636. https://doi.org/10.1080/15548627.2017.1423439.
NavaneethaKrishnan S, Rosales JL, Lee KY (2020) mPTP opening caused by Cdk5 loss is due to increased mitochondrial Ca(2+) uptake. Oncogene 39(13):2797–2806. https://doi.org/10.1038/s41388-020-1188-5
Nitta M, Kozono D, Kennedy R et al (2011) Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy. PLoS One 6(4). https://doi.org/10.1371/annotation/9b9cc4ae-ad56-464f-ab97-59f096b5c0eb
Papaioannou A, Chevet E (2018) Driving cancer tumorigenesis and metastasis through UPR signaling. Curr Top Microbiol Immunol 414:159–192. https://doi.org/10.1007/82_2017_36.
Peñaranda Fajardo NM, Meijer C, Kruyt FA (2016) The endoplasmic reticulum stress/unfolded protein response in gliomagenesis, tumor progression and as a therapeutic target in glioblastoma. Biochem Pharmacol 118:1–8. https://doi.org/10.1016/j.bcp.2016.04.008
Peñaranda-Fajardo NM, Meijer C, Liang Y et al (2019) ER stress and UPR activation in glioblastoma: identification of a noncanonical PERK mechanism regulating GBM stem cells through SOX2 modulation. Cell Death Dis 10(10):690. https://doi.org/10.1038/s41419-019-1934-1.
Pinton P, Giorgi C, Siviero R et al (2008) Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene 27(50):6407–6418. https://doi.org/10.1038/onc.2008.308.
Pudełek M, Król K, Catapano J et al (2020) Epidermal growth factor (EGF) augments the invasive potential of human glioblastoma Multiforme cells via the activation of collaborative EGFR/ROS-dependent signaling. Int J Mol Sci 21(10):3605. https://doi.org/10.3390/ijms21103605
Rinaldi M, Caffo M, Minutoli L et al (2016) ROS and brain gliomas: an overview of potential and innovative therapeutic strategies. Int J Mol Sci 17(6) pii: E984. https://doi.org/10.3390/ijms17060984
Santoso NG, Cebotaru L, Guggino WB (2011) Polycystin-1, 2, and STIM1 interact with IP(3)R to modulate ER Ca release through the PI3K/Akt pathway. Cell Physiol Biochem 27(6):715–726. https://doi.org/10.1159/000330080.
Seidlmayer LK, Juettner VV, Kettlewell S et al (2015) Distinct mPTP activation mechanisms in ischaemia-reperfusion: contributions of Ca2+, ROS, pH, and inorganic polyphosphate. Cardiovasc Res 106(2):237–248. https://doi.org/10.1093/cvr/cvv097.
Senft D, Ronai ZA (2015) UPR, autophagy, and mitochondria crosstalk underlies the ER stress response. Trends Biochem Sci 40(3):141–148. https://doi.org/10.1016/j.tibs.2015.01.002.
Shea A, Harish V, Afzal Z et al (2016) MicroRNAs in glioblastoma multiforme pathogenesis and therapeutics. Cancer Med 5(8):1917–1946. https://doi.org/10.1002/cam4.775
Song M, Chen D, Yu SP (2014) The TRPC channel blocker SKF 96365 inhibits glioblastoma cell growth by enhancing reverse mode of the Na+/Ca2+ exchanger and increasing intracellular Ca2+. Br J Pharmacol 171(14):3432–3447. https://doi.org/10.1111/bph.12691
Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8(7):579–591. https://doi.org/10.1038/nrd2803.
Valko M, Rhodes CJ, Moncol J et al (2006) Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact 160(1):1–40. https://doi.org/10.1016/j.cbi.2005.12.009.
Vimalraj S, Bhuvaneswari S, Lakshmikirupa S et al (2018) Nitric oxide signaling regulates tumor-induced intussusceptive-like angiogenesis. Microvasc Res 119:47–59. https://doi.org/10.1016/j.mvr.2018.04.001.
Visa A, Sallán MC, Maiques O et al (2019) T-type Cav3.1 channels mediate progression and chemotherapeutic resistance in glioblastoma. Cancer Res 79(8):1857–1868. https://doi.org/10.1158/0008-5472.CAN-18-1924
Wang Z, Dabrosin C, Yin X et al (2015) Broad targeting of angiogenesis for cancer prevention and therapy. Semin Cancer Biol 35(Suppl):S224–S243. https://doi.org/10.1016/j.semcancer.2015.01.001
Wang Q, Wang H, Jia Y et al (2017) Luteolin induces apoptosis by ROS/ER stress and mitochondrial dysfunction in gliomablastoma. Cancer Chemother Pharmacol 79(5):1031–1041. https://doi.org/10.1007/s00280-017-3299-4.
Weyemi U, Redon CE, Parekh PR, Dupuy C, Bonner WM (2013) NADPH oxidases NOXs and DUOXs as putative targets for cancer therapy. Anti Cancer Agents Med Chem 13(3):502–514
Xu Y, Krukoff TL (2005) Adrenomedullin stimulates nitric oxide release from SK-N-SH human neuroblastoma cells by modulating intracellular calcium mobilization. Endocrinology 146(5):2295–2305. https://doi.org/10.1210/en.2004-1354
Xu C, Wu X, Zhu J (2013) VEGF promotes proliferation of human glioblastoma multiforme stem-like cells through VEGF receptor 2. Sci World J 2013:417413. https://doi.org/10.1155/2013/417413
Yakovlev VA (2015) Nitric oxide: genomic instability and synthetic lethality. Redox Biol 5:414. https://doi.org/10.1016/j.redox.2015.09.013
Yu MO, Park KJ, Park DH et al (2015) Reactive oxygen species production has a critical role in hypoxia-induced Stat3 activation and angiogenesis in human glioblastoma. J Neuro-Oncol 125(1):55–63. https://doi.org/10.1007/s11060-015-1889-8
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Nasrin, T., Chakraborti, S., Shaikh, S. (2021). Reactive Species and ER-Mitochondrial Performance for Glioblastoma Multiforme Treatment Strategy. In: Chakraborti, S., Ray, B.K., Roychowdhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-4501-6_20-1
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