Clostridium botulinum neurotoxin A inhibits DBTRG glioblastoma cell proliferation and TRPV1 channel signaling pathways
Abstract
Prevalence of glioblastomas is high within the adult brain tumors and the proliferation of the glioblastomas was induced by excessive Ca2+ influx. Ca2+ permeable TRPV1 channel is gated by capsaicin and reactive oxygen species (ROS), although its activity was decreased in neurons by AMG and antioxidants. Clostridium
botulinum neurotoxin A (BotxA) acted antioxidant action in several cells and its treatment modulated TRPV1 in neurons. Hence, treatment of BotxA may modulate
glioblastoma cell proliferation and death via inhibition of TRPV1 in the DBTRG glioblastoma in vitro cell line model. The DBTRG cells were divided into three groups as control, BotxA (5 IU for 24 hours) and BotxA+TRPV1 channel blocker (AMG and 1 µM for 30 min). Intracellular Ca2+ response to TRPV1 activation was increased in the cells from capsaicin, although it was reduced by the BotxA and AMG. BotxA treatment decreased cell proliferation, although its treatment increased cell death (propidium iodide/Hoechst rate). In addition, BotxA decreased mitochondrial membrane depolarization levels, cytosolic and mitochondrial ROS generation in the cells. Their levels were further decreased in the BotxA+AMG group by the AMG treatment. The antiproliferative and neurotoxic effects of BotxA were shown to be exerted via modulation of oxidative stress and TRPV1 activation. BotxA could be used as an effective agent in the treatment of glioblastoma proliferation.
Supporting Institution
BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture, Industry and Trade Limited Company (Göller Bölgesi Teknokenti, Isparta, Turkey).
Project Number
2018-32
References
- Akpınar H, Nazıroğlu M, Övey İS, Çiğ B, Akpınar O. (2016). The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels. Sci Rep. 6:37196.
- Alptekin M, Eroglu S, Tutar E, Sencan S, Geyik MA, Ulasli M, Demiryurek AT, Camci C. (2015). Gene expressions of TRP channels in glioblastoma multiforme and relation with survival. Tumour Biol. 36(12):9209-9213.
- Amantini C, Mosca M, Nabissi M, Lucciarini R, Caprodossi S, Arcella A, Giangaspero F, Santoni G. (2007). Capsaicin-induced apoptosis of glioma cells is mediated by TRPV1 vanilloid receptor and requires p38 MAPK activation. J Neurochem. 102(3):977-990.
- Ataizi ZS, Ertilav K, Nazıroğlu M. (2019). Mitochondrial oxidative stress-induced brain and hippocampus apoptosis decrease through modulation of caspase activity, Ca(2+) influx and inflammatory cytokine molecular pathways in the docetaxel-treated mice by melatonin and selenium treatments. Metab Brain Dis. 34(4):1077-1089.
- Bandala C, Perez-Santos JL, Lara-Padilla E, Delgado Lopez G, AnayaRuiz M. (2013). Effect of botulinum toxin A on proliferation and apoptosis in the T47D breast cancer cell line. Asian Pac J Cancer Prev. 14(2):891-894.
- Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. (1997). The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389(6653):816-24.
- Chien CT, Lee HM, Wu CC, Li PC. (2012). Inhibitory effect of botulinum toxin type A on the NANC system in rat respiratory models of neurogenic inflammation. Arch Biochem Biophys. 524(2):106-113.
- Clapham DE. (2003). TRP channels as cellular sensors. Nature 426(6966):517-524.
- da Silva LB, Poulsen JN, Arendt-Nielsen L, Gazerani P. (2015). Botulinum neurotoxin type A modulates vesicular release of glutamate from satellite glial cells. J Cell Mol Med. 19(8):1900-1909.
- Deveci HA, Akyuva Y, Nur G, Nazıroğlu M. (2019). Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line. Biomed Pharmacother. 111:292-304.
- Ertilav K. (2019). Pregabalin protected cisplatin-induced oxidative neurotoxicity in neuronal cell line. J Cell Neurosci Oxid Stress. 11 (1): 815-824.
- Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee ShU. (2017). Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev. 18(1):3-9.
Abstract
Project Number
2018-32
References
- Akpınar H, Nazıroğlu M, Övey İS, Çiğ B, Akpınar O. (2016). The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels. Sci Rep. 6:37196.
- Alptekin M, Eroglu S, Tutar E, Sencan S, Geyik MA, Ulasli M, Demiryurek AT, Camci C. (2015). Gene expressions of TRP channels in glioblastoma multiforme and relation with survival. Tumour Biol. 36(12):9209-9213.
- Amantini C, Mosca M, Nabissi M, Lucciarini R, Caprodossi S, Arcella A, Giangaspero F, Santoni G. (2007). Capsaicin-induced apoptosis of glioma cells is mediated by TRPV1 vanilloid receptor and requires p38 MAPK activation. J Neurochem. 102(3):977-990.
- Ataizi ZS, Ertilav K, Nazıroğlu M. (2019). Mitochondrial oxidative stress-induced brain and hippocampus apoptosis decrease through modulation of caspase activity, Ca(2+) influx and inflammatory cytokine molecular pathways in the docetaxel-treated mice by melatonin and selenium treatments. Metab Brain Dis. 34(4):1077-1089.
- Bandala C, Perez-Santos JL, Lara-Padilla E, Delgado Lopez G, AnayaRuiz M. (2013). Effect of botulinum toxin A on proliferation and apoptosis in the T47D breast cancer cell line. Asian Pac J Cancer Prev. 14(2):891-894.
- Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. (1997). The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389(6653):816-24.
- Chien CT, Lee HM, Wu CC, Li PC. (2012). Inhibitory effect of botulinum toxin type A on the NANC system in rat respiratory models of neurogenic inflammation. Arch Biochem Biophys. 524(2):106-113.
- Clapham DE. (2003). TRP channels as cellular sensors. Nature 426(6966):517-524.
- da Silva LB, Poulsen JN, Arendt-Nielsen L, Gazerani P. (2015). Botulinum neurotoxin type A modulates vesicular release of glutamate from satellite glial cells. J Cell Mol Med. 19(8):1900-1909.
- Deveci HA, Akyuva Y, Nur G, Nazıroğlu M. (2019). Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line. Biomed Pharmacother. 111:292-304.
- Ertilav K. (2019). Pregabalin protected cisplatin-induced oxidative neurotoxicity in neuronal cell line. J Cell Neurosci Oxid Stress. 11 (1): 815-824.
- Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee ShU. (2017). Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev. 18(1):3-9.
Details
| Primary Language | English |
|---|---|
| Subjects | Neurosciences |
| Journal Section | Original Articles |
| Authors | |
| Project Number | 2018-32 |
| Publication Date | October 12, 2020 |
| Published in Issue | Year 2020 Volume: 12 Issue: 1 |