Inhibitory Effect of Bojungbangam-tang Kakambang on Cisplatin-Induced G2/M Phase Arrest in Human Renal Proximal Tubular HK-2 Cells

보정방암탕가감방(保正防癌湯加減方)이 cisplatin으로 유도된 인간 근위세뇨관 HK-2세포의 G2/M phase arrest에 미치는 영향

  • Park, Sung-Cheul (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Lee, Su-Kyung (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Yeom, Seung-Ryong (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Kwon, Young-Dal (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Song, Yung-Sun (Department of Oriental Rehabilitation Medicine, College of Oriental Medicine, Wonkwang University)
  • 박성철 (원광대학교 한의과대학 한방재활의학과교실) ;
  • 이수경 (원광대학교 한의과대학 한방재활의학과교실) ;
  • 염승룡 (원광대학교 한의과대학 한방재활의학과교실) ;
  • 권영달 (원광대학교 한의과대학 한방재활의학과교실) ;
  • 송용선 (원광대학교 한의과대학 한방재활의학과교실)
  • Published : 2007.12.25

Abstract

To idenifty effect of Bojungbangam-tang kakambang on Cisplatin-Induced G2/M Phase Arrest in Human Renal Proximal Tubular HK-2 Cells. Cytotoxicity of cisplatin was detected in HK-2 cells and the value of IC50 is about $25\;{\mu}M$. The treatment of cisplatin to HK-2 showed the G2/M phase cell cycle arrest. The ethanol extract of Bojungbangam-tang kakambang (EBTKB), a new herbal prescription composed of ten crude herbs, inhibited cisplatin-induced G2/M phase arrest in HK-2 cells. EBTKB increased G0/G1 peak in cisplatin-treated HK-2 cells. p53, p21 and p27 expression were increased in cisplatin-treated HK-2 cells. Inhibitory effect of EBTKB on cisplatin-induced G2/M phase arrest was accomplished through inhibition of p53, p21 and p27 expression. Also, reduced CDK2 and cyclin A expression by cisplatin were increased by EBTKB, but cyclin E was not changed. Reduction of ERK activation and increment of p38 activation by cisplatin were increased ERK activation and decreased p38 activation by EBTKB. Cisplatin had no effect on JNK activation, but EBTKB increased JNK activation. These results can suggest that EBTKB inhibits cisplatin-induced G2/M phase arrest in HK-2 cell through reduction of p53-dependent p21 and p27 protein, ERK activation and p38 inactivation.

Keywords

References

  1. Timmer-Bosscha, H., Mulder, N.H., de Vries, E.G. Modulation of cis-diamminedichloroplatinum(II) resistance: a review. Br J Cancer 66: 227-238, 1992 https://doi.org/10.1038/bjc.1992.249
  2. Goldstein, R.S., Mayor, G.H. Minireview. The nephrotoxicity of cisplatin. Life Sci 32: 685-690, 1983 https://doi.org/10.1016/0024-3205(83)90299-0
  3. Safirstein, R., Winston, J., Goldstein, M., Moel, D., Dikman, S., Guttenplan, J. Cisplatin nephrotoxicity. Am J Kidney Dis 8: 356-367, 1986 https://doi.org/10.1016/S0272-6386(86)80111-1
  4. Eastman, A. The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes. Pharmacol Ther 34: 155-166, 1987 https://doi.org/10.1016/0163-7258(87)90009-X
  5. Siddik, Z.H. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22: 7265-7279, 2003 https://doi.org/10.1038/sj.onc.1206933
  6. Cross, T.G., Scheel-Toellner, D., Henriquez, N.V., Deacon, E., Salmon, M., Lord, J.M. Serine/threonine protein kinases and apoptosis. Exp Cell Res 256: 34-41, 2000 https://doi.org/10.1006/excr.2000.4836
  7. Pearson, G., Robinson, F., Beers Gibson, T., Xu, B.E., Karandikar, M., Berman, K., Cobb, M.H. Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 22: 153-183, 2001 https://doi.org/10.1210/er.22.2.153
  8. Bedi, A., Barber, J.P., Bedi, G.C., el-Deiry, W.S., Sidransky, D., Vala, M.S., Akhtar, A.J., Hilton, J., Jones, R.J. BCR-ABL-mediated inhibition of apoptosis with delay of G2/M transition after DNA damage: a mechanism of resistance to multiple anticancer agents. Blood 86: 1148-1158, 1995
  9. Latif, C., Harvey, S.H., O'Connell, M.J. Ensuring the stability of the genome: DNA damage checkpoints. ScientificWorldJournal 1: 684-702, 2001 https://doi.org/10.1100/tsw.2001.297
  10. Schwartz, D., Almog, N., Peled, A., Goldfinger, N., Rotter, V. Role of wild type p53 in the G2 phase: regulation of the gamma-irradiation-induced delay and DNA repair. Oncogene 15: 2597-2607, 1997 https://doi.org/10.1038/sj.onc.1201436
  11. Tomasevic, G., Kamme, F., Stubberod, P., Wieloch, M., Wieloch, T. The tumor suppressor p53 and its response gene p21WAF1/Cip1 are not markers of neuronal death following transient global cerebral ischemia. Neuroscience 90: 781-792, 1999 https://doi.org/10.1016/S0306-4522(98)00484-9
  12. in, Z., Lim, S., Viani, M.A., Sapp, M., Lim, M.S. Down-regulation of telomerase activity in malignant lymphomas by radiation and chemotherapeutic agents. Am J Pathol 159: 711-719, 2001 https://doi.org/10.1016/S0002-9440(10)61742-7
  13. Miyaji, T., Kato, A., Yasuda, H., Fujigaki, Y., Hishida, A. Role of the increase in p21 in cisplatin-induced acute renal failure in rats. J Am Soc Nephrol 12: 900-908, 2001
  14. Shankland, S.J., Wolf, G. Cell cycle regulatory proteins in renal disease: role in hypertrophy, proliferation, and apoptosis. Am J Physiol Renal Physiol 278: F515-529, 2000 https://doi.org/10.1152/ajprenal.2000.278.4.F515
  15. Sherr, C.J., Roberts, J.M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev 13: 1501-1512, 1999 https://doi.org/10.1101/gad.13.12.1501
  16. Kastan, M.B., Onyekwere, O., Sidransky, D., Vogelstein, B., Craig, R.W. Participation of p53 protein in the cellular response to DNA damage. Cancer Res 56: 892-898, 1996
  17. Harris, C.C. Structure and function of the p53 tumor suppressor gene: clues for rational cancer therapeutic strategies. J Natl Cancer Inst 88: 1442-1455, 1996 https://doi.org/10.1093/jnci/88.20.1442
  18. Stewart, N., Hicks, G.G., Paraskevas, F., Mowat, M. Evidence for a second cell cycle block at G2/M by p53. Oncogene 10: 109-115, 1995
  19. garwal, M.L., Agarwal, A., Taylor, W.R., Stark, G.R. p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. Proc Natl Acad Sci USA 92: 8493-8497, 1995
  20. Cobb, M.H. MAP kinase pathways. Prog Biophys Mol Biol 71: 479-500, 1999 https://doi.org/10.1016/S0079-6107(98)00056-X
  21. Xia, Z., Dickens, M., Raingeaud, J., Davis, R.J., Greenberg, M.E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326-1331, 1995 https://doi.org/10.1126/science.270.5240.1326
  22. Davis RJ. Signal transduction by the JNK group of MAP kinases. Cell 103: 239-252, 2000 https://doi.org/10.1016/S0092-8674(00)00116-1
  23. Lee, S.J., Saiki, I., Hayakawa, Y., Nunome, S., Yamada, H., Kim, S.H. Antimetastatic and immunomodulating properties of a new herbal prescription, Bojung-bangamtang. Int Immunopharmacol 3: 147-157, 2000 https://doi.org/10.1016/S1567-5769(02)00091-7
  24. Kim, N.S., Ju, S.M., Kwon, Y.D., Shin, B.C., Ahn, K.S., Kim, S.H., Song, Y.S., Jeon, B.H. Anti-apoptotic effect of bojungbangam-tang ethanol extract on cisplatin-induced apoptosis in rat mesnagial cells. J Orient Physiol Pathol 20: 1664-1671, 2006
  25. Kwon, K.B., Kim, E.K., Lee, Y.R., Ju, S.M., Ryu, D.G., Kim, S.H., Jeon, B.H. Protective effects of sanyakbojungbangam-tang ethanol extracts on cisplatin-induced apoptosis in ECV304 cells. J Orient Physiol Pathol 20: 20-24, 2006
  26. Lee, E.O., Shim, B.S., Surh, Y.J., Jeon, B..H, Ahn, K.S., Kim, S.H. Study on the anti-angiogenic activity of ethanol extract of bojungbangam-tang. J Orient Physiol Pathol 20: 15-19, 2006
  27. Orren, D.K., Petersen, L.N., Bohr, V.A. Persistent DNA damage inhibits S-phase and G2 progression, and results in apoptosis. Mol Biol Cell 8: 1129-1142, 1997 https://doi.org/10.1091/mbc.8.6.1129
  28. Fujimoto, K., Hosotani, R., Doi, R., Wada, M., Lee, J.U., Koshiba, T., Miyamoto, Y., Tsuji, S., Nakajima, S., Imamura, M. Induction of cell-cycle arrest and apoptosis by a novel retinobenzoic-acid derivative, TAC-101, in human pancreatic-cancer cells. Int J Cancer 81: 637-644, 1999 https://doi.org/10.1002/(SICI)1097-0215(19990517)81:4<637::AID-IJC21>3.0.CO;2-4
  29. Gamet-Payrastre, L., Li, P., Lumeau, S., Cassar, G., Dupont, M.A., Chevolleau, S., Gasc, N., Tulliez, J., Terce, F. Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res 60: 1426-1433, 2000
  30. O'Connor, P.M., Ferris, D.K., Pagano, M., Draetta, G., Pines, J., Hunter, T., Longo, D.L., Kohn, K.W. G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2 and cyclin B1/cdc2-kinase complexes differently. J Biol Chem 268: 8298-8308, 1993
  31. Murray, A.W. Recycling the cell cycle: cyclins revisited. Cell 116: 221-234, 2004 https://doi.org/10.1016/S0092-8674(03)01080-8
  32. Covacci, V., Bruzzese, N., Sgambato, A., Di Francesco, A., Russo, M.A., Wolf, F.I., Cittadini, A. Magnesium restriction induces granulocytic differentiation and expression of p27Kip1 in human leukemic HL-60 cells. J Cell Biochem 70: 313-322, 1998 https://doi.org/10.1002/(SICI)1097-4644(19980901)70:3<313::AID-JCB4>3.0.CO;2-Q
  33. Sherr, C.J. Roberts, J.M. Inhibitors of mammalian G1 cyclin-dependent kinases. Genes Dev 9: 1149-1163, 1995 https://doi.org/10.1101/gad.9.10.1149
  34. Peter, M. Herskowitz I. Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle. Cell 79: 233-244, 1994 https://doi.org/10.1016/0092-8674(94)90193-7
  35. Elledge, S.J. Harper, J.W. Cdk inhibitors: on the threshold of checkpoints and development. Curr Opin Cell Biol 6: 847-852, 1994 https://doi.org/10.1016/0955-0674(94)90055-8
  36. Brugarolas, J., Chandrasekaran, C., Gordon, J.I., Beach, D., Jacks, T., Hannon, G.J. Radiation-induced cell cycle arrest compromised by p21 deficiency. Nature 377: 552-557, 1995 https://doi.org/10.1038/377552a0
  37. Owa, T., Yoshino, H., Yoshimatsu, K., Nagasu, T. Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents. Curr Med Chem 8: 1487-1503, 2001 https://doi.org/10.2174/0929867013371996
  38. el-Deiry, W.S., Tokino, T., Velculescu, V.E., Levy, D.B., Parsons, R., Trent, J.M., Lin, D., Mercer, W.E., Kinzler, K.W., Vogelstein, B. WAF1, a potential mediator of p53 tumor suppression. Cell 75: 817-825, 1993 https://doi.org/10.1016/0092-8674(93)90500-P
  39. He, G., Siddik, Z.H., Huang, Z., Wang, R., Koomen, J., Kobayashi, R., Khokhar, A.R., Kuang, J. Induction of p21 by p53 following DNA damage inhibits both Cdk4 and Cdk2 activities. Oncogene 24: 2929-2943, 2005 https://doi.org/10.1038/sj.onc.1208474
  40. Igata, M., Motoshima, H., Tsuruzoe, K., Kojima, K., Matsumura, T., Kondo, T., Taguchi, T., Nakamaru, K., Yano, M., Kukidome, D., Matsumoto, K., Toyonaga, T., Asano, T., Nishikawa, T., Araki, E. Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression. Circ Res 97: 837-844, 2005 https://doi.org/10.1161/01.RES.0000185823.73556.06
  41. right, J.W., Stouffer, R.L., Rodland, K.D. High-dose estrogen and clinical selective estrogen receptor modulators induce growth arrest, p21, and p53 in primate ovarian surface epithelial cells. J Clin Endocrinol Metab 90: 3688-3695, 2005 https://doi.org/10.1210/jc.2004-2456
  42. Cummings, B.S., Schnellmann, R.G. Cisplatin-induced renal cell apoptosis: caspase 3-dependent and -independent pathways. J Pharmacol Exp Ther 302: 8-17, 2002 https://doi.org/10.1124/jpet.302.1.8
  43. Jiang, M., Yi, X., Hsu, S., Wang, C.Y., Dong, Z. Role of p53 in cisplatin-induced tubular cell apoptosis: dependence on p53 transcriptional activity. Am J Physiol Renal Physiol 287: F1140-1147, 2004 https://doi.org/10.1152/ajprenal.00262.2004
  44. Baliga, R., Ueda, N., Walker, P.D., Shah, S.V. Oxidant mechanisms in toxic acute renal failure. Drug Metab Rev 31: 971-997, 1999 https://doi.org/10.1081/DMR-100101947
  45. Nath, K.A., Norby, S.M. Reactive oxygen species and acute renal failure. Am J Med 109: 665-678, 2000 https://doi.org/10.1016/S0002-9343(00)00612-4
  46. Martindale, J.L., Holbrook, N.J. Cellular response to oxidative stress: signaling for suicide and survival. J Cell Physiol 192: 1-15, 2002 https://doi.org/10.1002/jcp.10119
  47. Takahashi, Y., Ogra, Y., Suzuki, K.T. Synchronized generation of reactive oxygen species with the cell cycle. Life Sci 75: 301-311, 2004 https://doi.org/10.1016/j.lfs.2003.12.014
  48. Helt, C.E., Rancourt, R.C., Staversky, R.J., O'Reilly, M.A. p53-dependent induction of p21(Cip1/WAF1/Sdi1) protects against oxygen-induced toxicity. Toxicol Sci 63: 214-222, 2001 https://doi.org/10.1093/toxsci/63.2.214
  49. 권승봉. 원색임상본초학. 영림사, 1992
  50. Xia, Z., Dickens, M., Raingeaud, J., Davis, R.J., Greenberg, M.E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270: 1326-1331, 1995 https://doi.org/10.1126/science.270.5240.1326
  51. Klekotka, P.A., Santoro, S.A., Wang, H., Zutter, M.M. Specific residues within the alpha 2 integrin subunit cytoplasmic domain regulate migration and cell cycle progression via distinct MAPK pathways. J Biol Chem 276: 32353-32361, 2001 https://doi.org/10.1074/jbc.M101921200
  52. Roulston, A., Reinhard, C., Amiri, P., Williams, L.T. Early activation of c-Jun N-terminal kinase and p38 kinase regulate cell survival in response to tumor necrosis factor alpha. J Biol Chem 273: 10232-10239, 1998 https://doi.org/10.1074/jbc.273.17.10232
  53. Nagata, Y., Todokoro, K. Requirement of activation of JNK and p38 for environmental stress-induced erythroid differentiation and apoptosis and of inhibition of ERK for apoptosis. Blood 94: 853-863, 1999
  54. Guadagno, T.M., Ferrell, J.E. Jr. Requirement for MAPK activation for normal mitotic progression in Xenopus egg extracts. Science 282: 1312-1315, 1998 https://doi.org/10.1126/science.282.5392.1312
  55. Wright, J.H., Munar, E., Jameson, D.R., Andreassen, P.R., Margolis, R.L., Seger, R., Krebs, E.G. Mitogen-activated protein kinase kinase activity is required for the G(2)/M transition of the cell cycle in mammalian fibroblasts. Proc Natl Acad Sci USA 96: 11335-11340, 1999
  56. Bulavin, D.V., Higashimoto, Y., Popoff, I.J., Gaarde, W.A., Basrur, V., Potapova, O., Appella, E., Fornace, A.J. Jr. Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase. Nature 411: 102-107, 2001 https://doi.org/10.1038/35075107
  57. Wang, X., McGowan, C.H., Zhao, M., He, L., Downey, J.S., Fearns, C., Wang, Y., Huang, S., Han, J. Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol 20: 4543-4552, 2000 https://doi.org/10.1128/MCB.20.13.4543-4552.2000
  58. Bulavin, D.V., Higashimoto, Y., Popoff, I.J., Gaarde, W.A., Basrur, V., Potapova, O., Appella, E., Fornace, A.J. Jr. Initiation of a G2/M checkpoin after ultraviolet radiation requires p38 kinase. Nature 411: 102-107, 2001 https://doi.org/10.1038/35075107
  59. Wang, X., McGowan, C.H., Zhao, M., He, L., Downey, J.S., Fearns, C., Wang, Y., Huang, S., Han, J. Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest. Mol Cell Biol 20: 4543-4552, 2000 https://doi.org/10.1128/MCB.20.13.4543-4552.2000
  60. Huang, C., Ma, W.Y., Maxiner, A., Sun, Y., Dong, Z. p38 kinase mediates UV-induced phosphorylation of p53 protein at serine 389. J Biol Chem 274: 12229-12235, 1999 https://doi.org/10.1074/jbc.274.18.12229
  61. Takekawa, M., Adachi, M., Nakahata, A., Nakayama, I., Itoh, F., Tsukuda, H., Taya, Y., Imai, K. p53-inducible Wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. EMBO J 19: 6517-6526, 2000 https://doi.org/10.1093/emboj/19.23.6517
  62. Sanchez-Prieto, R., Rojas, J.M., Taya, Y., Gutkind, J.S. A role for the p38 mitogen-activated protein kinase pathway in the transcriptional activation of p53 on genotoxic stress by chemotherapeutic agents. Cancer Res 60: 2464-2472, 2000
  63. DeHaan, R.D., Yazlovitskaya, E.M., Persons, D.L. Regulation of p53 target gene expression by cisplatin-induced extracellular signal-regulated kinase. Cancer Chemother. Pharmacol 48: 383-388, 2001 https://doi.org/10.1007/s002800100318
  64. Hayakawa, J., Ohmichi, M., Kurachi, H., Ikegami, H., Kimura, A., Matsuoka, T., Jikihara, H., Mercola, D., Murata, Y. Inhibition of extracellular signal-regulated protein kinase or c-Jun N-terminal protein kinase cascade, differentially activated by cisplatin, sensitizes human ovarian cancer cell line. J Biol Chem 274: 31648-31654, 1999 https://doi.org/10.1074/jbc.274.44.31648
  65. Persons, D.L., Yazlovitskaya, E.M., Pelling, J.C. Effect of extracellular signal-regulated kinase on p53 accumulation in response to cisplatin. J Biol Chem 275: 35778-357785, 2000 https://doi.org/10.1074/jbc.M004267200