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Selenium enhances TRPA1 channel-mediated activity of temozolomide in SH-SY5Y neuroblastoma cells

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A Correction to this article was published on 31 March 2020

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Abstract

Purpose

Neuroblastoma is a malignant solid tumor that originates from the sympathetic nervous system in early childhood. Temozolomide is used for treatment in high-risk groups with low treatment response of neuroblastomas. TRPA1 channels in neuroblastoma cells are calcium permeable channels that can be activated by reactive oxygen species (ROT). In this study, we aimed to evaluate the level of activity of temozolomide and selenium in neuroblastoma cells via TRPA1 channels.

Method

Seven main groups were formed using SH-SY5Y neuroblastoma cells. The control was divided into temozolomide (TMZ) (100 μM, 24 h), TMZ+SEL+AP18, SEL (sodium selenite, 100 μM, 24 h), and SEL+AP18 groups. Intergroup calcium signaling, intracellular reactive oxygen species, caspase-3 and caspase-9, and mitochondrial depolarization analyses were performed by channel activation with TRPA1 agonist cinnamaldehyde in all groups.

Results

Cytosolic calcium concentration, apoptosis, caspase-3 and caspase-9 activation, mitochondrial membrane depolarization, and ROT levels were higher in TMZ (p < 0.001), TMZ+SEL (p < 0.001), and SEL (p < 0.05) groups than the control group. TRPA1 was lower in TTMZ+AP18, TMZ+SEL+AP18, and SEL+AP18 groups with channel blockers than respectively TMZ, TMZ+SEL, and SEL groups without channel blockers (p < 0.05).

Conclusion

The use of selenium with temozolomide increased the apoptotic efficacy of temozolomide via TRPA1 channels on tumor cells.

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Change history

  • 31 March 2020

    The original version of this article unfortunately contained few errors. The dose of sodium selenite was incorrectly indicated as 100 μM in the published version of “Selenium enhances TRPA1 channel-mediated activity of temozolomide in SH-SY5Y neuroblastoma cells”. The correct indication of sodium selenite is 5 µM. Additionally the authors accidenttally referred to reference 11 instead of reference 10 in Group 6.   

References

  1. Zhou MJ, Doral MY, DuBois SG, Villablanca JG, Yanik GA, Matthay KK (2015) Different outcomes for relapsed versus refractory neuroblastoma after therapy with 131I-metaiodobenzylguanidine (131I-MIBG). Eur J Cancer 51(16):2465–2472. https://doi.org/10.1016/j.ejca.2015.07.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Zage PE (2018) Novel therapies for relapsed and refractory neuroblastoma. Children 5:148. https://doi.org/10.3390/children5110148

    Article  PubMed Central  Google Scholar 

  3. Herd F, Basta NO, McNally RJQ, Tweddle DA (2019) A systematic review of re-induction chemotherapy for children with relapsed high-risk neuroblastoma. Eur J Cancer 111:50–58. https://doi.org/10.1016/j.ejca.2018.12.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Thomas A, Tanaka M, Trepel J, Reinhold WC, Rajapakse VN, Pommier Y (2017) Temozolomide in the era of precision medicine. Cancer Res 77:823–826. https://doi.org/10.1158/0008-5472.CAN-16-2983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Chen L, Pastorino F, Berry P, Bonner J, Kirk C, Wood KM, Thomas HD, Zhao Y, Daga A, Veal GJ, Lunec J, Newell DR, Ponzoni M, Tweddle DA (2019) Preclinical evaluation of the first intravenous small molecule MDM2 antagonist alone and in combination with temozolomide in neuroblastoma. Int J Cancer 144:3146–3159. https://doi.org/10.1002/ijc.32058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. DuBois SG, Mosse YP, Fox E, Kudgus RA, Reid JM, McGovern R, Groshen S, Bagatell R, Maris JM, Twist CJ, Goldsmith K, Granger MM, Weiss B, Park JR, Macy ME, Cohn SL, Yanik G, Wagner LM, Hawkins R, Courtier J, Lai H, Goodarzian F, Shimada H, Boucher N, Czarnecki S, Luo C, Tsao-Wei D, Matthay KK, Marachelian A (2018) Phase II trial of alisertib in combination with ırinotecan and temozolomide for patients with relapsed or refractory neuroblastoma. Clin Cancer Res 24(24):6142–6149. https://doi.org/10.1158/1078-0432.CCR-18-1381

    Article  PubMed  PubMed Central  Google Scholar 

  7. Modak S, Kushner BH, Basu E, Roberts SS, Cheung NK (2017) Combination of bevacizumab, irinotecan and temozolomide for refractory or relapsed neuroblastoma: results of a phase II study. Pediatr Blood Cancer 64:1–14. https://doi.org/10.1002/pbc.26448

    Article  CAS  Google Scholar 

  8. Sarada SKS, Himadri P, Ruma D, Sharma SK, Pauline T, Mrinalini (2008) Selenium protects the hypoxia induced apoptosis in neuroblastoma cells through upregulation of Bcl-2. Brain Res 1209:29–39. https://doi.org/10.1016/j.brainres.2008.02.041

    Article  CAS  PubMed  Google Scholar 

  9. Yakubov E, Buchfelder M, Eyüpoglu IY, Savaskan NE (2014) Selenium action in neuro-oncology. Biol Trace Elem Res 161:246–254. https://doi.org/10.1007/s12011-014-0111-8

    Article  CAS  PubMed  Google Scholar 

  10. Lee YJ, Kım JE, Kwak MH, Go J, Yang SY, Kwon HS et al (2014) Selenium treatment significantly inhibits tumor necrosis factor-a-İnduced cell death and tau hyperphosphorylation in neuroblastoma cells. Mol Med Rep 10:1869–1874. https://doi.org/10.3892/mmr.2014.2442

    Article  CAS  PubMed  Google Scholar 

  11. Misra S, Niyogi S (2009) Selenite causes cytotoxicity in rainbow trout (oncorhynchus mykiss) hepatocytes by inducing oxidative stress. Toxicol in Vitro 23:1249–1258. https://doi.org/10.1016/j.tiv.2009.07.031

    Article  CAS  PubMed  Google Scholar 

  12. Miller BA, Cheung JY (2016) TRPM2 protects against tissue damage following oxidative stress and ischaemia–reperfusion. J Physiol 594:4181–4191. https://doi.org/10.1113/JP270934

    Article  CAS  PubMed  Google Scholar 

  13. Christensen AP, Corey DP (2007) TRP channels in mechanosensation: direct or indirect activation? Nat Rev Neurosci 8:510–521. https://doi.org/10.1038/nrn2149

    Article  CAS  PubMed  Google Scholar 

  14. Bessac BF, Jordt SE (2008) Breathtaking TRP channels: TRPA1 and TRPV1 in airway chemosensation and reflex control. Physiology 23:360–370. https://doi.org/10.1152/physiol.00026.2008

    Article  CAS  PubMed  Google Scholar 

  15. Miller BA, Zhang W (2011) TRP channels as mediators of oxidative stress. Adv Exp Med Biol 704:531–544. https://doi.org/10.1007/978-94-007-0265-3_29

    Article  CAS  PubMed  Google Scholar 

  16. Kozai D, Ogawa N, Mori Y (2014) Redox regulation of transient receptor potential channels. Antioxid Redox Signal 21(6):971–986. https://doi.org/10.1089/ars.2013.5616

    Article  CAS  PubMed  Google Scholar 

  17. Simon F, Varela D, Cabello-Verrugio C (2013) Oxidative stress-modulated TRPM ion channels in cell dysfunction and pathological conditions in humans. Cell Signal 25(7):1614–1624. https://doi.org/10.1016/j.cellsig.2013.03.023

    Article  CAS  PubMed  Google Scholar 

  18. Clapham DE (2003) TRP channels as cellular sensors. Nature 426(6966):517–524. https://doi.org/10.1038/nature02196

    Article  CAS  PubMed  Google Scholar 

  19. Nishida M, Kuwahara K, Kozai D, Sakaguchi R, Mori Y (2015) TRP channels: their function and potentiality as drug targets. In: Nakao K, Minato N, Uemoto S (eds) Innovative medicine, 1st edn. Springer, Tokyo, pp 195–218

    Chapter  Google Scholar 

  20. Patapoutian A, Peier AM, Story GM, Viswanath V (2003) ThermoTRP channels and beyond mechanisms of temperature sensation. Nat Rev Neurosci 4(7):529–539. https://doi.org/10.1038/nrn1141

    Article  CAS  PubMed  Google Scholar 

  21. Morgan K, Sadofsky LR, Morice AH (2015) Genetic variants affecting human TRPA1 or TRPM8 structure can be classified in vitro as ‘well expressed’, ‘poorly expressed’ or ‘salvageable’. Bıoscıence Rep 35:1–13. https://doi.org/10.1042/BSR20150108

    Article  CAS  Google Scholar 

  22. Kádková A, Synytsya V, Krusek J, Zímová L, Vlachová V (2017) Molecular basis of TRPA1 regulation in nociceptive neurons. A review. Physiol Res 66:425–439. https://doi.org/10.33549/physiolres.933553

    Article  PubMed  Google Scholar 

  23. Shapovalov G, Ritaine A, Skryma R, Prevarskaya N (2016) Role of TRP ion channels in cancer and tumorigenesis. Semin Immunopathol 38:357–369. https://doi.org/10.1007/s00281-015-0525-1

    Article  CAS  PubMed  Google Scholar 

  24. Mori Y, Takahashi N, Kurokawa T, Kiyonaka S (2017) TRP channels in oxygen physiology: distinctive functional properties and roles of TRPA1 in O2 sensing. Proc Jpn Acad Ser B 93:464–482. https://doi.org/10.2183/pjab.93.028

    Article  CAS  Google Scholar 

  25. Merrill AW, Cuellar JM, Judd JH, Carstens MI, Carstens E (2008) Effects of TRPA1 agonists mustard oil and cinnamaldehyde on lumbar spinal wide-dynamic range neuronal responses to ınnocuous and noxious cutaneous stimuli in rats. J Neurophysiol 99:415–425. https://doi.org/10.1152/jn.00883.2007

    Article  CAS  PubMed  Google Scholar 

  26. Shi L, Fei X, Wang Z (2015) Demethoxycurcumin was prior to temozolomide on inhibiting proliferation and induced apoptosis of glioblastoma stem cells. Tumour Biol 36:7107–7119. https://doi.org/10.1007/s13277-015-3427-x

    Article  CAS  PubMed  Google Scholar 

  27. Martinez NA, Ayala AM, Martinez M, Martinez-Rivera FJ, Miranda JD, Silva WI (2016) Caveolin-1 regulates the P2Y2 receptor signaling in human 1321N1 astrocytoma cells. J Biol Chem 291(23):12208–12222. https://doi.org/10.1074/jbc.M116.730226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Bejarano I, Espino J, Barriga C, Reiter RJ, Pariente JA, Rodríguez AB (2011) Pro oxidant effect of melatonin in tumour leucocytes: relation with its cytotoxic and pro-apoptotic effects. Basic Clin Pharmacol Toxicol 108(1):14–20. https://doi.org/10.1111/j.1742-7843.2010.00619.x

    Article  CAS  PubMed  Google Scholar 

  29. Uğuz AC, Nazıroğlu M (2012) Effects of selenium on calcium signaling and apoptosis in rat dorsal root ganglion neurons induced by oxidative stress. Neurochem Res 37:1631–1638. https://doi.org/10.1007/s11064-012-0758-5

    Article  CAS  PubMed  Google Scholar 

  30. Öz A, Çelik Ö (2016) Curcumin inhibits oxidative stress-induced TRPM2 channel activation calcium ion entry and apoptosis values in SH-SY5Y neuroblastoma cells: involvement of transfection procedure. Mol Membr Biol 33:76–88. https://doi.org/10.1080/09687688.2017.1318224

    Article  CAS  PubMed  Google Scholar 

  31. Uguz AC, Cig B, Espino J, Bejarano I, Naziroglu M, Rodríguez AB, Pariente JA (2012) Melatonin potentiates chemotherapy-induced cytotoxicity and apoptosis in rat pancreatic tumor cells. J Pineal Res 53:91–98. https://doi.org/10.1111/j.1600-079X.2012.00974.x

    Article  CAS  PubMed  Google Scholar 

  32. Yürüker V, Nazıroğlu M, Şenol N (2015) Reduction in traumatic brain injury-induced oxidative stress, apoptosis, and calcium entry in rat hippocampus by melatonin: possible involvement of TRPM2 channels. Metab Brain Dis 30(1):223–231. https://doi.org/10.1007/s11011-014-9623-3

    Article  CAS  PubMed  Google Scholar 

  33. Ray SK (2019) Neuroblastoma molecular mechanisms and therapeutic interventions. Elsevier Science, London

    Google Scholar 

  34. Montell C, Rubin GM (1989) Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 20:1313–1323. https://doi.org/10.1016/0896-6273(89)90069-X

    Article  Google Scholar 

  35. Fels B, Bulk E, Petho Z, Schwab A (2018) The role of TRP channels in the metastatic cascade. Pharmaceuticals 11:48–73. https://doi.org/10.3390/ph11020048

    Article  CAS  PubMed Central  Google Scholar 

  36. Wang T, Chen Z, Zhu Y, Pan Q, Liu Y, Qi X, Jin L, Jin J, Ma X, Hua D (2015) Inhibition of transient receptor potential channel 5 reverses 5-fluorouracil resistance in human colorectal cancer cells. J Biol Chem 290(1):448–456. https://doi.org/10.1074/jbc.M114.590364

    Article  CAS  PubMed  Google Scholar 

  37. Bollimuntha S, Singh BB, Shavali S, Sharma SK, Ebadi M (2005) TRPC1-mediated ınhibition of 1-Methyl-4-phenylpyridinium ıon neurotoxicity in human SH-SY5Y neuroblastoma cells. J Biol Chem 280:2132–2140. https://doi.org/10.1074/jbc.M407384200

    Article  CAS  PubMed  Google Scholar 

  38. Lam PMW, Hainsworth AH, Smith GD, Owen DE, Davies J, Lambert DG (2007) Activation of recombinant human TRPV1 receptors expressed in SH-SY5Y human neuroblastoma cells increases [Ca2+]i, initiates neurotransmitter release and promotes delayed cell death. J Neurochem 102:801–811. https://doi.org/10.1111/j.1471-4159.2007.04569.x

    Article  CAS  PubMed  Google Scholar 

  39. Louhıvuorı LM, Bart G, Larsson KP, Louhıvuorı V, Näsman J, Nordström T, Koıvısto AP, Åkerman KEO (2009) Differentiation dependent expression of TRPA1 and TRPM8 channels in IMR-32 human neuroblastoma cells. J Cell Physiol 221:67–74. https://doi.org/10.1002/jcp.21828

    Article  CAS  PubMed  Google Scholar 

  40. Çıtışlı V, Dodurga Y, Eroğlu C, Seçme M, Avcı ÇB, Şatıroğlu TNL (2015) Temozolomide may induce cell cycle arrest by interacting with URG4/URGCP in SH-SY5Y neuroblastoma cells. Tumor Biol 36:6765–6772. https://doi.org/10.1007/s13277-015-3373-7

    Article  CAS  Google Scholar 

  41. Maraldi T, Riccio M, Zambonin L, Vinceti M, De Pol A, Hakim G (2011) Low levels of selenium compounds are selectively toxic for a human neuron cell line through ROS/RNS increase and apoptotic process activation. Neurotoxicology 32:180–187. https://doi.org/10.1016/j.neuro.2010.10.008

    Article  CAS  PubMed  Google Scholar 

  42. Cheng Y, Sk UH, Zhang Y, Ren X, Zhang L, Kathryn J et al (2012) Rational ıncorporation of selenium into temozolomide elicits superior antitumor activity associated with both apoptotic and autophagic cell death. PLoS One. https://doi.org/10.1371/journal.pone.0035104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nabissi M, Morelli MB, Santomi M, Santoni G (2013) Triggering of the TRPV2 channel by cannabidiol sensitizes glioblastoma cells to cytotoxic chemotherapeutic agents. Carcinogenesis 34:48–57. https://doi.org/10.1093/carcin/bgs328

    Article  CAS  PubMed  Google Scholar 

  44. Takahashi N, Chen HY, Harris IS, Stover DG, Selfors LM, Bronson RT et al (2018) Cancer cells coopt the neuronal redoxsensing channel TRPA1 to promote oxidative stress tolerance. Cancer Cell 33:985–1003. https://doi.org/10.1016/j.ccell.2018.05.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Espino J, Bejarano I, Redondo PC, Rosado JA, Barriga C, Reiter RJ et al (2010) Melatonin reduces apoptosis induced by calcium signaling in human leukocytes: evidence for the involvement of mitochondria and Bax activation. J MembrBiol 233(1–3):105–118. https://doi.org/10.1007/s00232-010-9230-0

    Article  CAS  Google Scholar 

  46. Nazıroğlu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001. https://doi.org/10.1007/s11064-007-9386-x

    Article  CAS  PubMed  Google Scholar 

  47. Sergeev IN (2005) Calcium signaling in cancer and vitamin D. J Steroid Biochem Mol Biol 97:145–151. https://doi.org/10.1016/j.jsbmb.2005.06.007

    Article  CAS  PubMed  Google Scholar 

  48. Doerner JF, Gisselmann G, Hatt H, Wetzel CH (2007) Transient receptor potential channel A1 is directly gated by calcium ions. J Biol Chem 282:13180–13189. https://doi.org/10.1074/jbc.M607849200

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Birol Özkal.

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Özkal, B., Övey, İ.S. Selenium enhances TRPA1 channel-mediated activity of temozolomide in SH-SY5Y neuroblastoma cells. Childs Nerv Syst 36, 1283–1292 (2020). https://doi.org/10.1007/s00381-020-04567-w

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