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Scorpion venom induces glioma cell apoptosis in vivo and inhibits glioma tumor growth in vitro

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Summary

Malignant gliomas are the main brain tumors notoriously resistant to currently available therapies, since they fail to undergo apoptosis upon anticancer treatment. Recent progress on enhanced studies of ion channels involved in glioma cells shed new light on the investigation of glioma cell growth and proliferation. Here we report BmK scorpion venom, a rich resource of various ion channels blockers/modulators, induces cell death of cultured malignant glioma U251-MG cells in vitro specifically at a dose of 10 mg/ml while shows no effect on human hepatocellular carcinoma cells and Chinese hamster ovary cells. The glioma cell death was then determined as apoptosis using 4,6-diamidino-2-phenylindole staining and fluorescence-activated cell sorting analysis. After incubation with BmK venom for 32 and 40 h, 36.20% and 63.08% of U251-MG cells showed apoptosis. Furthermore, BmK venom could significantly inhibit the tumor growth in vitro, which was assessed using U251-MG tumor xenografts on severe combined immunodeficiency mice. The tumor volume of the BmK venom treated mice is nearly 1/8 of that of control after 21 days, and the tumor weight is less than half of that of control. That BmK venom induces apoptosis and inhibits growth of glioma may result from the inhibition and/or modulation of various ion channels in glioma cells.

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References

  1. EC Burton MD. Prados (2000) ArticleTitleMalignant gliomas Curr Treat Options Oncol. 1 459–468 Occurrence Handle1:STN:280:DC%2BD38zhsFSqtw%3D%3D Occurrence Handle12057153

    CAS  PubMed  Google Scholar 

  2. P Kleihues DN Louis BW Scheithauer LB Rorke G Reifenberger PC Burger WK. Cavenee (2002) ArticleTitleThe WHO classification of tumors of the nervous system J Neuropathol Exp Neurol. 61 215–225 Occurrence Handle11895036

    PubMed  Google Scholar 

  3. ER Laws SuffixJr. K. Thapar (1993) ArticleTitleBrain tumors CA Cancer J Clin. 43 263–271 Occurrence Handle8364768

    PubMed  Google Scholar 

  4. M Schrey C Codina R Kraft C Beetz R Kalff S Wolfl S. Patt (2002) ArticleTitleMolecular characterization of voltage-gated sodium channels in human gliomas Neuroreport. 13 2493–2498 Occurrence Handle10.1097/00001756-200212200-00023 Occurrence Handle1:CAS:528:DC%2BD38Xpslarsbg%3D Occurrence Handle12499855

    Article  CAS  PubMed  Google Scholar 

  5. K Preussat C Beetz M Schrey R Kraft S Wolfl R Kalff S. Patt (2003) ArticleTitleExpression of voltage-gated potassium channels Kv1.3 and Kv1.5 in human gliomas Neurosci Lett. 346 33–36 Occurrence Handle10.1016/S0304-3940(03)00562-7 Occurrence Handle1:CAS:528:DC%2BD3sXltF2gtr4%3D Occurrence Handle12850541

    Article  CAS  PubMed  Google Scholar 

  6. CB Ransom H. Sontheimer (2001) ArticleTitleBK channels in human glioma cells J Neurophysiol. 85 790–803 Occurrence Handle1:CAS:528:DC%2BD3MXktVaqt7c%3D Occurrence Handle11160513

    CAS  PubMed  Google Scholar 

  7. X Liu Y Chang PH Reinhart H Sontheimer Y. Chang (2002) ArticleTitleCloning and characterization of glioma BK, a novel BK channel isoform highly expressed in human glioma cells J Neurosci. 22 1840–1849 Occurrence Handle1:CAS:528:DC%2BD38XhvValurk%3D Occurrence Handle11880513

    CAS  PubMed  Google Scholar 

  8. ML Olsen S Schade SA Lyons MD Amaral H. Sontheimer (2003) ArticleTitleExpression of voltage-gated chloride channels in human glioma cells J Neurosci. 23 5572–5582 Occurrence Handle1:CAS:528:DC%2BD3sXltl2qsLw%3D Occurrence Handle12843258

    CAS  PubMed  Google Scholar 

  9. YJ Li YH. Ji (2000) ArticleTitleBinding characteristics of BmK I, an alpha-like scorpion neurotoxic polypeptide, on cockroach nerve cord synaptosomes J Pept Res. 56 195–200 Occurrence Handle10.1034/j.1399-3011.2000.00750.x Occurrence Handle1:CAS:528:DC%2BD3cXnslOjtL8%3D Occurrence Handle11083058

    Article  CAS  PubMed  Google Scholar 

  10. YJ Li Y Liu YH. Ji (2000) ArticleTitleBmK AS: New scorpion neurotoxin binds to distinct receptor sites of mammal and insect voltage-gated sodium channels J Neurosci Res. 61 541–548 Occurrence Handle10.1002/1097-4547(20000901)61:5<541::AID-JNR9>3.0.CO;2-# Occurrence Handle1:CAS:528:DC%2BD3cXmsFGqur4%3D Occurrence Handle10956424

    Article  CAS  PubMed  Google Scholar 

  11. ZY Tan H Xiao X Mao CY Wang ZQ Zhao YH. Ji (2001) ArticleTitleThe inhibitory effects of BmK IT2, a scorpion neurotoxin on rat nociceptive flexion reflex and a possible mechanism for modulating voltage-gated Na+ channels Neuropharmacology. 40 352–357 Occurrence Handle10.1016/S0028-3908(00)00168-4 Occurrence Handle1:CAS:528:DC%2BD3MXpslOnsg%3D%3D Occurrence Handle11166328

    Article  CAS  PubMed  Google Scholar 

  12. YH Ji WX Wang Q Wang YP. Huang (2002) ArticleTitleThe binding of BmK abT, a unique neurotoxin, to mammal brain and insect Na+ channels using biosensor Eur J Pharmacol. 454 25–30 Occurrence Handle10.1016/S0014-2999(02)02363-4 Occurrence Handle1:CAS:528:DC%2BD38Xot1ahtbY%3D Occurrence Handle12409001

    Article  CAS  PubMed  Google Scholar 

  13. QC Tong Y Zhang DP Li ZN Zhou YH. Ji (2000) ArticleTitleThe blocking effect of BmP02, one novel short-chain scorpion peptide on transient outward K+ channel of adult rat ventricular myocyte Regul Pept. 90 85–92 Occurrence Handle10.1016/S0167-0115(00)00116-6 Occurrence Handle1:CAS:528:DC%2BD3cXjs1Grtr8%3D Occurrence Handle10828497

    Article  CAS  PubMed  Google Scholar 

  14. YH Ji WX Wang JG Ye LL He YJ Li YP Yan Z. Zhou (2003) ArticleTitleMartentoxin, a novel K+-channel-blocking peptide: purification, cDNA and genomic cloning, and electrophysiological and pharmacological characterization J Neurochem. 84 325–335 Occurrence Handle10.1046/j.1471-4159.2003.01516.x Occurrence Handle1:CAS:528:DC%2BD3sXmtFKluw%3D%3D Occurrence Handle12558995

    Article  CAS  PubMed  Google Scholar 

  15. CJ. Hawkins (2004) ArticleTitleTRAIL and malignant glioma Vitam Horm. 67 427–452 Occurrence Handle1:CAS:528:DC%2BD2cXltlKgtb4%3D Occurrence Handle15110189

    CAS  PubMed  Google Scholar 

  16. XY Zhang JW Zhang B Chen ZT Bai J Shen YH. Ji (2002) ArticleTitleDynamic determination and possible mechanism of amino acid transmitter release from rat spinal dorsal horn induced by the venom and a neurotoxin (BmK I) of scorpion Buthus martensi Karsch Brain Res Bull. 58 27–31 Occurrence Handle10.1016/S0361-9230(02)00752-9 Occurrence Handle1:CAS:528:DC%2BD38Xlt12ktLg%3D Occurrence Handle12121809

    Article  CAS  PubMed  Google Scholar 

  17. B Chen C Wang Y. Ji (2001) ArticleTitleScorpion BmK venom induces nociceptive response of rats by plantar injection Neurotoxicol Teratol. 23 675–679 Occurrence Handle10.1016/S0892-0362(01)00174-X Occurrence Handle1:CAS:528:DC%2BD38XktFCnuw%3D%3D Occurrence Handle11792536

    Article  CAS  PubMed  Google Scholar 

  18. B Chen X Zhuo C Wang Y. Ji (2002) ArticleTitleAsian scorpion BmK venom induces plasma extravasation and thermal hyperalgesia in the rat Toxicon. 40 527–533 Occurrence Handle10.1016/S0041-0101(01)00248-3 Occurrence Handle1:CAS:528:DC%2BD38XnvVyqtQ%3D%3D Occurrence Handle11821124

    Article  CAS  PubMed  Google Scholar 

  19. JA DeBin JE Maggio GR. Strichartz (1993) ArticleTitlePurification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion Am J Physiol. 264 C361–369 Occurrence Handle1:CAS:528:DyaK3sXmtF2nsLg%3D Occurrence Handle8383429

    CAS  PubMed  Google Scholar 

  20. C Goudet CW Chi J. Tytgat (2002) ArticleTitleAn overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch Toxicon. 40 1239–1258 Occurrence Handle10.1016/S0041-0101(02)00142-3 Occurrence Handle1:CAS:528:DC%2BD38XmslKrsL4%3D Occurrence Handle12220709

    Article  CAS  PubMed  Google Scholar 

  21. D Basrai R Kraft C Bollensdorff L Liebmann K Benndorf S. Patt (2002) ArticleTitleBK channel blockers inhibit potassium-induced proliferation of human astrocytoma cells Neuroreport. 13 403–407 Occurrence Handle10.1097/00001756-200203250-00008 Occurrence Handle1:CAS:528:DC%2BD38XnsFKkurs%3D Occurrence Handle11930149

    Article  CAS  PubMed  Google Scholar 

  22. A Bordey H Sontheimer J. Trouslard (2000) ArticleTitleMuscarinic activation of BK channels induces membrane oscillations in glioma cells and leads to inhibition of cell migration J Membr Biol. 176 31–40 Occurrence Handle10.1007/s002320001073 Occurrence Handle1:CAS:528:DC%2BD3cXkvFCktLg%3D Occurrence Handle10882426

    Article  CAS  PubMed  Google Scholar 

  23. R Kraft P Krause S Jung D Basrai L Liebmann J Bolz S. Patt (2003) ArticleTitleBK channel openers inhibit migration of human glioma cells Pflugers Arch. 446 248–255 Occurrence Handle1:CAS:528:DC%2BD3sXlt1aisr4%3D Occurrence Handle12739163

    CAS  PubMed  Google Scholar 

  24. H Koegel S Kaesler R Burgstahler S Werner C. Alzheimer (2003) ArticleTitleUnexpected down-regulation of the hIK1 Ca2+-activated K+ channel by its opener 1-ethyl-2-benzimidazolinone in HaCaT keratinocytes Inverse effects on cell growth and proliferation. J Biol Chem. 278 3323–3330 Occurrence Handle1:CAS:528:DC%2BD3sXmt1KjsA%3D%3D

    CAS  Google Scholar 

  25. ML Olsen H. Sontheimer (2004) ArticleTitleMislocalization of Kir channels in malignant glia Glia. 46 63–73 Occurrence Handle10.1002/glia.10346 Occurrence Handle1:STN:280:DC%2BD2c7gvVOqsg%3D%3D Occurrence Handle14999814

    Article  CAS  PubMed  Google Scholar 

  26. L Soroceanu TJ Manning SuffixJr. H. Sontheimer (1999) ArticleTitleModulation of glioma cell migration and invasion using Cl and K+ ion channel blockers J Neurosci. 19 5942–5954 Occurrence Handle1:CAS:528:DyaK1MXksVyktbo%3D Occurrence Handle10407033

    CAS  PubMed  Google Scholar 

  27. CB Ransom JT O’Neal H. Sontheimer (2001) ArticleTitleVolume-activated chloride currents contribute to the resting conductance and invasive migration of human glioma cells J Neurosci. 21 7674–7683 Occurrence Handle1:STN:280:DC%2BD3MritVShsA%3D%3D Occurrence Handle11567057

    CAS  PubMed  Google Scholar 

  28. H. Sontheimer (2003) ArticleTitleMalignant gliomas: perverting glutamate and ion homeostasis for selective advantage Trends Neurosci. 26 543–549 Occurrence Handle10.1016/j.tins.2003.08.007 Occurrence Handle1:CAS:528:DC%2BD3sXns1Cgurw%3D Occurrence Handle14522147

    Article  CAS  PubMed  Google Scholar 

  29. H. Sontheimer (2004) ArticleTitleIon channels and amino acid transporters support the growth and invasion of primary brain tumors Mol Neurobiol. 29 61–71 Occurrence Handle10.1385/MN:29:1:61 Occurrence Handle1:CAS:528:DC%2BD2cXjsFKkur8%3D Occurrence Handle15034223

    Article  CAS  PubMed  Google Scholar 

  30. JM Dubois B. Rouzaire-Dubois (1993) ArticleTitleRole of potassium channels in mitogenesis Prog Biophys Mol Bio. 59 1–21 Occurrence Handle10.1016/0079-6107(93)90005-5 Occurrence Handle1:CAS:528:DyaK3sXnsFCmuw%3D%3D

    Article  CAS  Google Scholar 

  31. LS Chin CC Park KM Zitnay M Sinha AJ DiPatri SuffixJr P Perillan JM. Simard (1997) ArticleTitle4-Aminopyridine causes apoptosis and blocks an outward rectifier K+ channel in malignant astrocytoma cell lines J Neurosci Res. 48 122–127 Occurrence Handle10.1002/(SICI)1097-4547(19970415)48:2<122::AID-JNR4>3.0.CO;2-E Occurrence Handle1:CAS:528:DyaK2sXivVGqtbc%3D Occurrence Handle9130140

    Article  CAS  PubMed  Google Scholar 

  32. YA Mei MM Wu CL Huan JT Sun HQ Zhou ZH. Zhang (2000) ArticleTitle4-Aminopyridine, a specific blocker of K+ channels, inhibited inward Na+ current in rat cerebellar granule cells Brain Res. 873 46–53 Occurrence Handle10.1016/S0006-8993(00)02469-0 Occurrence Handle1:CAS:528:DC%2BD3cXltVOmsbg%3D Occurrence Handle10915809

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Yong-Hua Ji.

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Wang, WX., Ji, YH. Scorpion venom induces glioma cell apoptosis in vivo and inhibits glioma tumor growth in vitro. J Neurooncol 73, 1–7 (2005). https://doi.org/10.1007/s11060-004-4205-6

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