Journal of Acupuncture Research

Korean Acupuncture & Moxibustion Medicine Society (대한침구의학회)
권호 표지
DOI QR코드

DOI QR Code

The Antitumor Mechanism and Effects of Tetrodotoxin: a Literature Review

복어독의 주성분인 Tetrodotoxin의 항암 기전, 효과에 대한 문헌 고찰

  • Cho, Ye Eun (Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Lee, Seungmin (Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Yoon, Kang Hyun (Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Lim, Ji Seok (Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Lee, Seung Hoon (Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Choi, Do Young (Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University) ;
  • Lee, Jae Dong (Department of Acupuncture & Moxibustion Medicine, College of Korean Medicine, Kyung Hee University)
  • 조예은 (경희대학교 한의과대학 침구의학교실) ;
  • 이승민 (경희대학교 한의과대학 침구의학교실) ;
  • 윤강현 (경희대학교 한의과대학 침구의학교실) ;
  • 임지석 (경희대학교 한의과대학 침구의학교실) ;
  • 이승훈 (경희대학교 한의과대학 침구의학교실) ;
  • 최도영 (경희대학교 한의과대학 침구의학교실) ;
  • 이재동 (경희대학교 한의과대학 침구의학교실)
  • Received : 2015.02.10
  • Accepted : 2015.02.28
  • Published : 2015.03.20
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : The purpose of this study is to explore the antitumor mechanism and effects of tetrodotoxin through a literature review of experimental and clinical studies. Methods : Medical databases, including The Cochrane Library, Pubmed, NDSL, RISS4u and National Assembly Library, were searched for relevant articles published from January 1, 2000 to October 31, 2014 using the keywords 'tetrodotoxin', 'cancer' and 'tumor'. The results were classified into experimental studies(in vitro and in vivo) and clinical studies. Analysis of the results was conducted on several research areas including the mechanism, antitumor effect and adverse effects of tetrodotoxin(TTX). Results : A total of 34 experimental studies(32 in vitro and 2 in vivo) and 3 clinical studies were found in the search. Most of the experimental studies suggested blocking of voltage-gated sodium channels in metastasis of tumor cells as the main antitumor mechanism of TTX. The most common type of cancers mentioned in the experimental studies were prostate and breast cancer. All of the clinical studies were on the application of TTX on moderate to severe cancer-related pain. No adverse effects of TTX were reported in in vivo studies but mild to moderate adverse events were reported in clinical studies. Conclusions : The results show that tetrodotoxin, which is the main component of Tetraodontidae(commonly known as pufferfish) poison, could be clinically used for antitumor therapy. However, further studies should be conducted on its safety.

Keywords

References

  1. Onkal R, Djamgoz MB. Molecular pharmacology of voltage-gated sodium channel expression in metastatic disease: clinical potential of neonatal Nav1.5 in breast cancer. Eur J Pharmacol. 2009 ; 625(1-3) : 206-19. https://doi.org/10.1016/j.ejphar.2009.08.040
  2. Hwang TJ, Kwon GR, Choe IS. Bibliographic studies on the tetrodotoxin(TTX). J of Korean Institute of Herbal-Acupuncture. 2000 ; 3(2) : 1-25.
  3. Campbell TM, Main MJ, Fitzgerald EM. Functional expression of the voltage-gated Na+-channel Na(v)1.7 is necessary for EGF-mediated invasion in human non-small cell lung cancer cells. J Cell Sci. 2013 ; 126(21) : 4939-49. https://doi.org/10.1242/jcs.130013
  4. Roger S, Rollin J, Barascu A et al. Voltage-gated sodium channels potentiate the invasive capacities of human non-small-cell lung cancer cell lines. Int J Biochem Cell Biol. 2007 ; 39(4) : 774-86. https://doi.org/10.1016/j.biocel.2006.12.007
  5. Onganer PU, Djamgoz MB. Small-cell lung cancer (human): potentiation of endocytic mem- brane activity by voltage-gated Na(+) channel expression in vitro. J Membr Biol. 2005 ; 204(2) : 67-75. https://doi.org/10.1007/s00232-005-0747-6
  6. Kawaguchi A, Asano H, Matsushima K, Wada T, Yoshida S, Ichida S. Enhancement of sodium current in NG108-15 cells during neural differentiation is mainly due to an increase in NaV1.7 expression. Neurochem Res. 2007 ; 32(9) : 1469-75. https://doi.org/10.1007/s11064-007-9334-9
  7. Kraft R, Basrai D, Benndorf K, Patt S. Serum deprivation and NGF induce and modulate voltagegated Na(+) currents in human astrocytoma cell lines. Glia. 2001 ; 34(1) : 59-67. https://doi.org/10.1002/glia.1040
  8. House CD, Vaske CJ, Schwartz AM et al. Voltagegated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion. Cancer Res. 2010 ; 70(17) : 6957-67. https://doi.org/10.1158/0008-5472.CAN-10-1169
  9. Maselli MA, Piepoli AL, Guerra V et al. Colonic smooth muscle responses in patients with diverticular disease of the colon: effect of the NK2 receptor antagonist SR48968. Dig Liver Dis. 2004 ; 36(5) : 348-54. https://doi.org/10.1016/j.dld.2004.01.014
  10. Gao R, Shen Y, Cai J, Lei M, Wang Z. Expression of voltage-gated sodium channel alpha subunit in human ovarian cancer. Oncol Rep. 2010 ; 23(5) : 1293-9.
  11. Fraser SP, Ozerlat-Gunduz I, Onkal R, Diss JK, Latchman DS, Djamgoz MB. Estrogen and nongenomic upregulation of voltage-gated Na(+) channel activity in MDA-MB-231 human breast cancer cells: role in adhesion. J Cell Physiol. 2010 ; 224(2) : 527-39. https://doi.org/10.1002/jcp.22154
  12. Chioni AM, Shao D, Grose R, Djamgoz MB. Protein kinase A and regulation of neonatal Nav1.5 expression in human breast cancer cells: activity- dependent positive feedback and cellular migration. Int J Biochem Cell Biol. 2010 ; 42(2) : 346-58. https://doi.org/10.1016/j.biocel.2009.11.021
  13. Krasowska M, Grzywna ZJ, Mycielska ME, Djamgoz MB. Fractal analysis and ionic depend- ence of endocytotic membrane activity of human breast cancer cells. Eur Biophys J. 2009 ; 38(8) : 1115-25. https://doi.org/10.1007/s00249-009-0516-z
  14. Gao R, Wang J, Shen Y, Lei M, Wang Z. Functional expression of voltage-gated sodium channels Nav1.5 in human breast cancer cell line MDA-MB-231. J Huazhong Univ Sci Technolog Med Sci. 2009 ; 29(1) : 64-7. https://doi.org/10.1007/s11596-009-0113-5
  15. Gillet L, Roger S, Besson P et al. Voltage-gated sodium channel activity promotes cysteine cathepsin- dependent invasiveness and colony growth of human cancer cells. J Biol Chem. 2009 ; 284 (13) : 8680-91. https://doi.org/10.1074/jbc.M806891200
  16. Tran TA, Gillet L, Roger S, Besson P, White E, Le Guennec JY. Non-anti-mitotic concentrations of taxol reduce breast cancer cell invasiveness. Biochem Biophys Res Commun. 2009 ; 379(2) : 304-8. https://doi.org/10.1016/j.bbrc.2008.12.073
  17. Fraser SP, Diss JK, Chioni AM et al. Voltagegated sodium channel expression and potentiation of human breast cancer metastasis. Clin Cancer Res. 2005 ; 11(15) : 5381-9. https://doi.org/10.1158/1078-0432.CCR-05-0327
  18. Roger S, Le Guennec JY, Besson P. Particular sensitivity to calcium channel blockers of the fast inward voltage-dependent sodium current involved in the invasive properties of a metastastic breast cancer cell line. Br J Pharmacol. 2004 ; 141(4) : 610-5. https://doi.org/10.1038/sj.bjp.0705649
  19. Roger S, Besson P, Le Guennec JY. Involvement of a novel fast inward sodium current in the invasion capacity of a breast cancer cell line. Biochim Biophys Acta. 2003 ; 1616(2) : 107-11. https://doi.org/10.1016/j.bbamem.2003.07.001
  20. Nakajima T, Kubota N, Tsutsumi T et al. Eicosapentaenoic acid inhibits voltage-gated sodium channels and invasiveness in prostate cancer cells. Br J Pharmacol. 2009 ; 156(3) : 420-31. https://doi.org/10.1111/j.1476-5381.2008.00059.x
  21. Uysal-Onganer P, Djamgoz MB. Epidermal growth factor potentiates in vitro metastatic behaviour of human prostate cancer PC-3M cells: involvement of voltage-gated sodium channel. Mol Cancer. 2007 ; 6 : 76. https://doi.org/10.1186/1476-4598-6-76
  22. Ding Y, Brackenbury WJ, Onganer PU et al. Epidermal growth factor upregulates motility of Mat-LyLu rat prostate cancer cells partially via voltage-gated Na+ channel activity. J Cell Physiol.2008 ; 215(1) : 77-81. https://doi.org/10.1002/jcp.21289
  23. Palmer CP, Mycielska ME, Burcu H et al. Single cell adhesion measuring apparatus(SCAMA): application to cancer cell lines of different metastatic potential and voltage-gated Na+ channel expression. Eur Biophys J. 2008 ; 37(4) : 359-68. https://doi.org/10.1007/s00249-007-0219-2
  24. Scorey N, Fraser SP, Patel P, Pridgeon C, Dallman MJ, Djamgoz MB. Notch signalling and voltage-gated Na+ channel activity in human prostate cancer cells: independent modulation of in vitro motility. Prostate Cancer Prostatic Dis. 2006 ; 9(4) : 399-406. https://doi.org/10.1038/sj.pcan.4500894
  25. Brackenbury WJ, Djamgoz MB. Activity-dependent regulation of voltage-gated Na+ channel expression in Mat-LyLu rat prostate cancer cell line. J Physiol. 2006 ; 573(Pt 2) : 343-56. https://doi.org/10.1113/jphysiol.2006.106906
  26. Mycielska ME, Palmer CP, Brackenbury WJ, Djamgoz MB. Expression of Na+-dependent citrate transport in a strongly metastatic human prostate cancer PC-3M cell line: regulation by voltagegated Na+ channel activity. J Physiol. 2005 ; 563(Pt 2) : 393-408. https://doi.org/10.1113/jphysiol.2004.079491
  27. Bennett ES, Smith BA, Harper JM. Voltage-gated Na+ channels confer invasive properties on human prostate cancer cells. Pflugers Arch. 2004 ; 447(6) : 908-14. https://doi.org/10.1007/s00424-003-1205-x
  28. Fraser SP, Salvador V, Manning EA et al. Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility. J Cell Physiol. 2003 ; 195(3) :479. https://doi.org/10.1002/jcp.10312
  29. Mycielska ME, Fraser SP, Szatkowski M, Djamgoz MB. Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: II. Secretory membrane activity. J Cell Physiol. 2003 ; 195(3) : 461-9. https://doi.org/10.1002/jcp.10265
  30. Djamgoz MBA, Mycielska M, Madeja Z, Fraser SP, Korohoda W. Directional movement of rat prostate cancer cells in direct-current electric field: involvement of voltagegated Na+ channel activity. J Cell Sci. 2001 ; 114(Pt 114) : 2697-705.
  31. Fraser SP, Grimes JA, Djamgoz MB. Effects of voltage-gated ion channel modulators on rat prostatic cancer cell proliferation: comparison of strongly and weakly metastatic cell lines. Prostate. 2000 ; 44(1) : 61-76. https://doi.org/10.1002/1097-0045(20000615)44:1<61::AID-PROS9>3.0.CO;2-3
  32. Carrithers MD, Chatterjee G, Carrithers LM et al. Regulation of podosome formation in macrophages by a splice variant of the sodium channel SCN8A. J Biol Chem. 2009 ; 284(12) : 8114-26. https://doi.org/10.1074/jbc.M801892200
  33. Randall A, McNaughton N, Green P. Properties of voltage-gated Na+ channels in the human rhabdomyosarcoma cell-line SJ-RH30: conventional and automated patch clamp analysis. Pharmacol Res. 2006 ; 54(2) : 118-28. https://doi.org/10.1016/j.phrs.2006.03.005
  34. Fulgenzi G, Graciotti L, Faronato M et al. Human neoplastic mesothelial cells express voltagegated sodium channels involved in cell motility. Int J Biochem Cell Biol. 2006 ; 38(7) : 1146-59. https://doi.org/10.1016/j.biocel.2005.12.003
  35. Yildirim S, Altun S, Gumushan H, Patel A, Djamgoz MB. Voltage-gated sodium channel activity promotes prostate cancer metastasis in vivo. Cancer Lett. 2012 ; 323(1) : 58-61. https://doi.org/10.1016/j.canlet.2012.03.036
  36. El-Dayem SM, Fouda FM, Ali EH, Motelp BA. The antitumor effects of tetrodotoxin and/or doxorubicin on Ehrlich ascites carcinoma-bearing female mice. Toxicol Ind Health. 2013 ; 29(5) : 404-17. https://doi.org/10.1177/0748233711434955
  37. Hagen NA, Fisher KM, Lapointe B et al. An openlabel, multi-dose efficacy and safety study of intramuscular tetrodotoxin in patients with severe cancer-related pain. J Pain Symptom Manage. 2007 ; 34(2) : 171-82. https://doi.org/10.1016/j.jpainsymman.2006.11.008
  38. Hagen NA, du Souich P, Lapointe B et al. Tetrodotoxin for moderate to severe cancer pain: a randomized, double blind, parallel design multicenter study. J Pain Symptom Manage. 2008 ; 35(4) : 420-9. https://doi.org/10.1016/j.jpainsymman.2007.05.011
  39. Hagen NA, Fisher KM, Lapointe B et al. A multicentre open-label safety and efficacy study of tetrodotoxin for cancer pain. Curr Oncol. 2011 ; 18(3) : e109-16.
  40. Hyun SH, Sohn CH, Ryoo SM, Oh BJ, Lim KS. Clinical analysis of puffer fish poisoning cases. J of the Korean Society of Clinical Toxicology. 2011 ; 9(2) : 95-100.