Journal of Pharmacopuncture (대한약침학회지)

KOREAN PHARMACOPUNCTURE INSTITUTE (대한약침학회)
권호 표지
DOI QR코드

DOI QR Code

Effects of Ulmi Pumilae Cortex on AGS Gastric Cancer Cells

  • Lim, Bora (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Lee, Hee Jung (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Kim, Min Chul (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine) ;
  • Kim, Byung Joo (Division of Longevity and Biofunctional Medicine, Pusan National University School of Korean Medicine)
  • Received : 2013.03.06
  • Accepted : 2013.04.19
  • Published : 2013.06.30
⟨ Previous Next ⟩

Abstract

Objective: Ulmi Pumilae Cortex (UPC) is a deciduous tree with uneven pinnate leaves and is classified as a subfamily of Ulmuceae and contains many pharmacologically active constituents. The aim of this study was to investigate the effects of UPC on the growth and survival of AGS cells, the most common human gastric adenocarcinoma cell lines. Methods: The AGS cells were treated with varying concentrations of UPC. Analyses of the sub G1, caspase-3 activity, and mitochondrial depolarization were conducted to determine whether AGS cell death occured by apoptosis. Furthermore, to identify the role of the transient receptor potential melastatin (TRPM) 7 channels in AGS cell growth and survival, we used human embryonic kidney (HEK) 293 cells overexpressed with TRPM7 channels. Results: The addition of UPC to a culture medium inhibited AGS cell growth and survival. Experimental results showed that the sub G1, caspase-3 activity, and mitochondrial depolarization were increased. Furthermore, TRPM7 channel overexpression in HEK 293 cells exacerbated UPC-induced cell death. Conclusion: These findings indicate that UPC inhibits the growth and survival of gastric cancer cells due to a blockade of the TRPM7 channel activity. Therefore, UPC is a potential drug for treatment of gastric cancer, and TRPM7 channels may play an important role in survival in cases of gastric cancer.

Keywords

Acknowledgement

Supported by : Pusan National University

References

  1. Rhyu JK, Yu BS, Jeong JE, Bak JY, Son IH, Lee JS, et al. [Studies on the apoptosis-inducing effect of Ulmi Pumilae Cortex on human leukemia HL-60 cells]. Korean J Oriental Physiology & Pathology. 2004;18(3):900-7. Korean.
  2. Rubnov S, Kashman Y, Rabinowitz R, Schlesinger M, Mechoulam R. Suppressors of cancer cellproliferation from fig (Ficus carica) resin: isolation and structure elucidation. J Nat Prod. 2001;64(7):993-6. https://doi.org/10.1021/np000592z
  3. Miller F, Ware G. Resistance of temperate Chinese elms (Ulmus spp.) to feeding by the adult elm leaf beetle (Coleoptera: Chrysomelidae ). J Econ Entomol. 2001;94(1):162-6.
  4. Kovacic P, Wakelin LP. Review: DNA molecular electrostatic potential: novel perspectives for the mechanism of action of anticancer drugs involving electron transfer and oxidative stress. Anticancer DrugDes. 2001;16(4-5):175-84.
  5. 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
  6. Clapham DE. TRP channels as cellular sensors. Nature. 2003;426(6966):517-24. https://doi.org/10.1038/nature02196
  7. Runnels LW, Yue L, Clapham DE. The TRPM7 channel is inactivated by PIP(2) hydrolysis. Nat Cell Biol. 2002;4(5):329-36. https://doi.org/10.1038/ncb781
  8. 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
  9. 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
  10. 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
  11. 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
  12. Nicoletti I, Migliorati G, Pagliacci MC, Grignani F, Riccardi C. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J Immunol Methods. 1991;139:271-9. https://doi.org/10.1016/0022-1759(91)90198-O
  13. Hellein KN, Kennedy EM, Harwood VJ, Gordon KV, Wang SY, Lepo JE. A filter-based propidium monoazide technique to distinguish live from membrane-compromised microorganisms using quantitative PCR. J Microbiol Methods. 2012;89(1):76-8. https://doi.org/10.1016/j.mimet.2012.01.015
  14. Wang BJ, Won SJ, Yu ZR, Su CL. Free radical scavenging and apoptotic effects of Cordycepin sinensis ractionated by supercritical carbon dioxide. Food Chem Toxicol. 2005;43(4):543-52. https://doi.org/10.1016/j.fct.2004.12.008
  15. Hotz MA, Gong J, Traganos F, Darzynkiewicz Z. Flow cytometric detection of apoptosis: comparison of the assays of in situ DNA degradation and chromatin changes. Cytometry. 1994;15(3):237-44. https://doi.org/10.1002/cyto.990150309
  16. Vermes I, Haanen C, Reutelingsperger C. Flow cytometry of apoptotic cell death. J Immunol Methods. 2000;243(1-2):167-90. https://doi.org/10.1016/S0022-1759(00)00233-7
  17. Nadler MJ, Hermosura MC, Inabe K, Perraud AL, Zhu Q, Stokes AJ, et al. LTRPC7 is a $Mg{\cdot}ATPregulated$ divalent cation channel required for cell viability. Nature. 2001;411(6837):590-5. https://doi.org/10.1038/35079092
  18. Bharti AC, Aggarwal BB. Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem Pharmacol. 2002;64(5-6):883-8. https://doi.org/10.1016/S0006-2952(02)01154-1
  19. Oren M, Damalas A, Gottlieb T, Michael D, Taplick J, Leal JF, et al. Regulation of p53: intricate loops and delicate balances. Ann N Y Acad Sci. 2002;973:374-83. https://doi.org/10.1111/j.1749-6632.2002.tb04669.x
  20. Cory S, Adams JM. The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2002;2(9):647-56. https://doi.org/10.1038/nrc883
  21. Abrams JM. Competition and compensation: coupled to death in development and cancer. Cell. 2002;110(4):403-6. https://doi.org/10.1016/S0092-8674(02)00904-2
  22. 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
  23. Razik MA, Cidlowski JA. Molecular interplay between ion channels and the regulation of apoptosis. Biol Res. 2002;35(2):203-7.
  24. Schonherr 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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
  31. 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
  32. 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
  33. 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
  34. 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
  35. Kim BJ. Involvement of transient receptor potential melastatin 7 channels in Sophorae Radix-induced apoptosis in cancer cells. Pharmacopuncture. 2012;15(3):31-8.
  36. Hwang MW, Kim HW, Kim BJ. Involvement of transient receptor potential melastatin 7 channels in orostachys Japonicus-induced apoptosis in cancer cells. Int J Pharmacol. 2012;8(7):638-46. https://doi.org/10.3923/ijp.2012.638.646
  37. Santoni G, Farfariello V. TRP channels and cancer: new targets for diagnosis and chemotherapy. Endocr Metab Immune Disord Drug Targets. 2011;11(1):54-67. https://doi.org/10.2174/187153011794982068

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