Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
권호 표지
DOI QR코드

DOI QR Code

Involvement of Transient Receptor Potential Melastatin 7 Channels in Sophorae Radix-induced Apoptosis in Cancer Cells - Sophorae Radix and TRPM7 -

  • Kim, Byung-Joo (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine)
  • Received : 2012.07.17
  • Accepted : 2012.09.10
  • Published : 2012.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Sophorae Radix (SR) plays a role in a number of physiologic and pharmacologic functions in many organs. Objective: The aim of this study was to clarify the potential role for transient receptor potential melastatin 7 (TRPM7) channels in SR-inhibited growth and survival of AGS and MCF-7 cells, the most common human gastric and breast adenocarcinoma cell lines. Methods: The AGS and the MCF-7 cells were treated with varying concentrations of SR. Analyses of the caspase-3 and - 9 activity, the mitochondrial depolarization and the poly (ADPribose) polymerase (PARP) cleavage were conducted to determine if AGS and MCF-7 cell death occured by apoptosis. TRPM7 channel blockers ($Gd^{3+}$ or 2-APB) and small interfering RNA (siRNA) were used in this study to confirm the role of TRPM7 channels. Furthermore, TRPM7 channels were overexpressed in human embryonic kidney (HEK) 293 cells to identify the role of TRPM7 channels in AGS and MCF-7 cell growth and survival. Results: The addition of SR to a culture medium inhibited AGS and MCF-7 cell growth and survival. Experimental results showed that the caspase-3 and -9 activity, the mitochondrial depolarization, and the degree of PARP cleavage was increased. TRPM7 channel blockade, either by $Gd^{3+}$ or 2-APB or by suppressing TRPM7 expression with small interfering RNA, blocked the SR-induced inhibition of cell growth and survival. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated SR-induced cell death. Conclusions: These findings indicate that SR inhibits the growth and survival of gastric and breast cancer cells due to a blockade of the TRPM7 channel activity. Therefore, TRPM7 channels may play an important role in the survival of patients with gastric and breast cancer.

Keywords

References

  1. Kim H, Lee MR, Lee GS, An WG, Cho SI. Effect of Sophora flavescens Aiton extract on degranulation of mast cells and contact dermatitis induced by dinitrofluorobenzene in mice. J Ethnopharmacol. 2012;142(1):253-8. https://doi.org/10.1016/j.jep.2012.04.053
  2. Liu T, Song Y, Chen H, Pan S, Sun X. Matrine inhibits proliferation and induces apoptosis of pancreatic cancer cells in vitro and in vivo. Biol Pharm Bull. 2010;33(10):1740-5. https://doi.org/10.1248/bpb.33.1740
  3. Ding Y, Tian RH, Kinjo J, Nohara T, Kitagawa I. Three new oleanene glycosides from Sophora flavescens. Chem Pharm Bull. 1992;40(11):2990-4. https://doi.org/10.1248/cpb.40.2990
  4. Woo ER, Kwak JH, Kim HJ, Park H. A new prenylated flavonol from the roots of Sophora flavescens. J Nat Prod. 1998;61(12):1552-4. https://doi.org/10.1021/np980103j
  5. Kang TH, Jeong SJ, Ko WG, Kim NY, Lee BH, Inagaki M, et al. Cytotoxic lavandulyl flavanones from Sophora flavescens. J Nat Prod. 2000;63(5):680-1. https://doi.org/10.1021/np990567x
  6. Son JK, Park JS, Kim JA, Kim Y, Chung SR, Lee SH. Prenylated flavonoids from the roots of Sophora flavescens with tyrosinase inhibitory activity. Planta Med. 2003;69(6):559-61. https://doi.org/10.1055/s-2003-40643
  7. Kim SJ, Son KH, Chang HW, Kang SS, Kim HP. Tyrosinase inhibitory prenylated flavonoids from Sophora flavescens. Biol Pharm Bull. 2003;26(9):1348-50. https://doi.org/10.1248/bpb.26.1348
  8. Ding P, Chen D, Bastow KF, Nyarko AK, Wang X, Lee KH. Cytotoxic isoprenylated flavonoids from the roots of Sophora flavescens. Helv Chim Acta. 2004;87(10):2574-80. https://doi.org/10.1002/hlca.200490230
  9. Sato S, Takeo J, Aoyama C, Kawahara H. Na+-glucose cotransporter (SGLT) inhibitory flavonoids from the roots of Sophora flavescens. Bioorg Med Chem. 2007;15(10):3445-9. https://doi.org/10.1016/j.bmc.2007.03.011
  10. De Naeyer A, Vanden Berghe W, Pocock V, Milligan S, Haegeman G, De Keukeleire D. Estrogenic and anticarcinogenic properties of kurarinone, a lavandulyl flavanone from the roots of Sophora flavescens. J Nat Prod. 2004;67(11):1829-32. https://doi.org/10.1021/np040069a
  11. Ryu YB, Curtis-Long MJ, Kim JH, Jeong SH, Yang MK, Lee KW, et al. Pterocarpans and flavanones from Sophora flavescens displaying potent neuraminidase inhibition. Bioorg Med Chem Lett. 2008;18(23):6046-9. https://doi.org/10.1016/j.bmcl.2008.10.033
  12. Kim BJ, Park EJ, Lee JH, Jeon JH, Kim SJ, So I. Suppression of transient receptor potential melastatin 7 channel induces cell death in gastric cancer. Cancer Sci. 2008;99(12):2502-9. https://doi.org/10.1111/j.1349-7006.2008.00982.x
  13. Guilbert A, Gautier M, Dhennin-Duthille I, Haren N, Sevestre H, Ouadid-Ahidouch H. Evidence that TRPM7 is required for breast cancer cell proliferation. Am J Physiol Cell Physiol. 2009;297(3):C493-502. https://doi.org/10.1152/ajpcell.00624.2008
  14. Clapham DE. TRP channels as cellular sensors. Nature. 2003;426(6966):517-24. https://doi.org/10.1038/nature02196
  15. Nadler MJ, Hermosura MC, Inabe K, Perraud AL, Zhu Q, Stokes AJ, et al. LTRPC7 is a Mg.ATP-regulated divalent cation channel required for cell viability. Nature. 2001;411(6837):590-5. https://doi.org/10.1038/35079092
  16. Runnels LW, Yue L, Clapham DE. TRP-PLIK, a bifunctional protein with kinase and ion channel activities. Science. 2001;291(5506):1043-7. https://doi.org/10.1126/science.1058519
  17. Jin J, Desai BN, Navarro B, Donovan A, Andrews NC, Clapham DE. Deletion of Trpm7 disrupts embryonic development and thymopoiesis without altering $Mg^{2+}$ homeostasis. Science. 2008;322(5902):756-60. https://doi.org/10.1126/science.1163493
  18. Jiang J, Li MH, Inoue K, Chu XP, Seeds J, Xiong ZG. Transient receptor potential melastatin 7-like current in human head and neck carcinoma cells: role in cell proliferation. Cancer Res. 2007;67(22):10929-38. https://doi.org/10.1158/0008-5472.CAN-07-1121
  19. Schmitz C, Perraud AL, Johnson CO, Inabe K, Smith MK, Penner R, et al. Regulation of vertebrate cellular $Mg^{2+}$ homeostasis by TRPM7. Cell. 2003;114(2):191-200. https://doi.org/10.1016/S0092-8674(03)00556-7
  20. Lang F, Foller M, Lang KS, Lang PA, Ritter M, Gulbins E, et al. Ion channels in cell proliferation and apoptotic cell death. J Membr Biol. 2005;205(3):147-57. https://doi.org/10.1007/s00232-005-0780-5
  21. Razik MA, Cidlowski JA. Molecular interplay between ion channels and the regulation of apoptosis. Biol Res. 2002;35(2):203-7.
  22. Scho..nherr R. Clinical relevance of ion channels for diagnosis and therapy of cancer. J Membr Biol. 2005;205(3):175-84. https://doi.org/10.1007/s00232-005-0782-3
  23. Lehen'kyi V, Shapovalov G, Skryma R, Prevarskaya N. Ion channnels and transporters in cancer. 5. Ion channels in control of cancer and cell apoptosis. Am J Physiol Cell Physiol. 2011;301(6):C1281-9. https://doi.org/10.1152/ajpcell.00249.2011
  24. Kunzelmann K: Ion channels and cancer. J Membr Biol. 2005;205(3):159-73. https://doi.org/10.1007/s00232-005-0781-4
  25. Abdul M, Hoosein N. Voltage-gated potassium ion channels in colon cancer. Oncol Rep. 2002;9(5):961-4.
  26. Abdul M, Hoosein N. Voltage-gated sodium ion channels in prostate cancer: expression and activity. Anticancer Res. 2002;22(3):1727-30.
  27. Jirsch J, Deeley RG, Cole SP, Stewart AJ, Fedida D. Inwardly rectifying $K^{+}$ channels and volume-regulated anion channels in multidrug-resistant small cell lung cancer cells. Cancer Res. 1993;53(18):4156-60.
  28. Shuba YM, Prevarskaya N, Lemonnier L, Van Coppenolle F, Kostyuk PG, Mauroy B, et al. Volume-regulated chloride conductance in the LNCaP human prostate cancer cell line. Am J Physiol Cell Physiol. 2000;279(4):C1144-1154. https://doi.org/10.1152/ajpcell.2000.279.4.C1144
  29. Kim BJ, Nah SY, Jeon JH, So I, Kim SJ. Transient receptor potential melastatin 7 channels are involved in ginsenoside Rg3-induced apoptosis in gastric cancer cells. Basic Clin Pharmacol Toxicol. 2011;109(4):233-9. https://doi.org/10.1111/j.1742-7843.2011.00706.x
  30. Owsianik G, D'Hoedt D, Voets T, Nilius B. Structure-function relationship of the TRP channel superfamily. Rev Physiol Biochem Pharmacol. 2006;156:61-90.
  31. Nilius B, Owsianik G, Voets T, Peters JA. Transient receptor potential cation channels in disease. Physiol Rev. 2007;87(1):165-217. https://doi.org/10.1152/physrev.00021.2006
  32. Shapovalov G, Lehen'kyi V, Skryma R, Prevarskaya N. TRP channels in cell survival and cell death in normal and transformed cells. Cell Calcium. 2011;50(3):295-302. https://doi.org/10.1016/j.ceca.2011.05.006
  33. Fixemer T, Wissenbach U, Flockerzi V, Bonkhoff H. Expression of the $Ca^{2+}$-selective cation channel TRPV6 in human prostate cancer: a novel prognostic marker for tumor progression. Oncogene. 2003;22(49):7858-61. https://doi.org/10.1038/sj.onc.1206895
  34. Domotor A, Peidl Z, Vincze A, Hunyady B, Szolcsa'nyi J, Kereskay L, et al. Immunohistochemical distribution of vanilloid receptor, calcitonin-gene related peptide and substance P in gastrointestinal mucosa of patients with different gastrointestinal disorders. Inflammopharmacology. 2005;13(1-3):161-77. https://doi.org/10.1163/156856005774423737
  35. Hartel M, di Mola FF, Selvaggi F, Mascetta G, Wente MN, Felix K, et al. Vanilloids in pancreatic cancer: potential for chemotherapy and pain management. Gut. 2006;55(4):519-28. https://doi.org/10.1136/gut.2005.073205
  36. Lazzeri M, Vannucchi MG, Spinelli M, Bizzoco E, Beneforti P, Turini D, et al. Transient receptor potential vanilloid type 1 (TRPV1) expression changes from normal urothelium to transitional cell carcinoma of human bladder. Eur Urol. 2005;48(4):691-8. https://doi.org/10.1016/j.eururo.2005.05.018
  37. Sanchez MG, Sanchez AM, Collado B, Malagarie-Cazenave S, Olea N, Carmena MJ, et al. Expression of the transient receptor potential vanilloid 1 (TRPV1) in LNCaP and PC-3 prostate cancer cells and in human prostate tissue. Eur J Pharmacol. 2005;515(1-3):20-7. https://doi.org/10.1016/j.ejphar.2005.04.010
  38. Duncan LM, Deeds J, Hunter J, Shao J, Holmgren LM, Woolf EA, et al. Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis. Cancer Res. 1998;58(7):1515-20.
  39. Tsavaler L, Shapero MH, Morkowski S, Laus R. Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins. Cancer Res. 2001;61(9):3760-9.
  40. Heshall SM, Afar DE, Hiller J, Horvath LG, Quinn DI, Rasiah KK, et al. Survival analysis of genome-wide gene expression profiles of prostate cancers identifies new prognostic targets of disease relapse. Cancer Res. 2003;63(14):4196-203.
  41. Minke B, CooK B. TRP channel proteins and signal transduction. Physiol Rev. 2002;82(2):429-72. https://doi.org/10.1152/physrev.00001.2002
  42. Montell C, Birnbaumer L, Flockerzi V. The TRP channels, a remarkably functional family. Cell. 2002;108(5):595-8. https://doi.org/10.1016/S0092-8674(02)00670-0
  43. Montell C. The TRP superfamily of cation channels. Sci STKE. 2005;2005(272):re3.
  44. He Y, Yao G, Savoia C, Touyz RM. Transient receptor potential melastatin 7 ion channels regulate magnesium homeostasis in vascular smooth muscle cells: role of angiotensin II. Circ Res 2005;96(2):207-15. https://doi.org/10.1161/01.RES.0000152967.88472.3e
  45. Hanano T, Hara Y, Shi J, Morita H, Umebayashi C, Mori E, et al. Involvement of TRPM7 in cell growth as a spontaneously activated $Ca^{2+}$ entry pathway in human retinoblastoma cells. J Pharmacol Sci. 2004;95(4):403-19. https://doi.org/10.1254/jphs.FP0040273
  46. Aarts M, Iihara K, Wei WL, Xiong ZG, Arundine M, Cerwinski W, et al. A key role for TRPM7 channels in anoxic neuronal death. Cell. 2003;115(7):863-77. https://doi.org/10.1016/S0092-8674(03)01017-1
  47. Krapivinsky G, Mochida S, Krapivinsky L, Cibulsky SM, Clapham DE. The TRPM7 ion channel functions in cholinergic synaptic vesicles and affects transmitter release. Neuron. 2006;52(3):485-96. https://doi.org/10.1016/j.neuron.2006.09.033
  48. Su D, May JM, Koury MJ, Asard H. Human erythrocyte membranes contain a cytochrome b561 that may be involved in extracellular ascorbate recycling. J Biol Chem. 2006;281(52):39852-9. https://doi.org/10.1074/jbc.M606543200
  49. Kim BJ, Lim HH, Yang DK, Jun JY, Chang IY, Park CS, et al. Melastatin-type transient receptor potential channel 7 is required for intestinal pacemaking activity. Gastroenterology. 2005;129(5):1504-17. https://doi.org/10.1053/j.gastro.2005.08.016
  50. Wykes RC, Lee M, Duffy SM, Yang W, Seward EP, Bradding P. Functional transient receptor potential melastatin 7 channels are critical for human mast cell survival. J Immunol. 2007;179(6):4045-52. https://doi.org/10.4049/jimmunol.179.6.4045
  51. Abed E, Moreau R. Importance of melastatin-like transient receptor potential 7 and cations (magnesium, calcium) in human osteoblast-like cell proliferation. Cell Prolif. 2007;40(6):849-65. https://doi.org/10.1111/j.1365-2184.2007.00476.x

Cited by

  1. Role of transient receptor potential melastatin type 7 channel in gastric cancer vol.5, pp.2, 2016, https://doi.org/10.1016/j.imr.2016.04.004
  2. Buxus Microphylla var. Koreana Nakai Extract for the Treatment of Gastric Cancer vol.16, pp.3, 2013, https://doi.org/10.3831/KPI.2013.16.016
  3. Linear Quantitative Profiling Method Fast Monitors Alkaloids of Sophora Flavescens That Was Verified by Tri-Marker Analyses vol.11, pp.8, 2016, https://doi.org/10.1371/journal.pone.0161146
  4. Apoptotic Effects and Involvement of TRPM7 Channels of the Traditional Herbal Medicine, Dangkwisoo-San in Gastric Cancer Cells vol.10, pp.7, 2014, https://doi.org/10.3923/ijp.2014.398.405