DOI QR코드

DOI QR Code

Arsenic Trioxide Promotes Paclitaxel Cytotoxicity in Resistant Breast Cancer Cells

  • 발행 : 2015.08.03

초록

A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

키워드

참고문헌

  1. Ali AY, Farrand L, Kim JY, et al (2012). Molecular determinants of ovarian cancer chemoresistance: new insights into an old conundrum. Ann NY Acad Sci, 1271, 58-67. https://doi.org/10.1111/j.1749-6632.2012.06734.x
  2. Baj G, Arnulfo A, Deaglio S, et al (2002). Arsenic trioxide and breast cancer: analysis of the apoptotic, differentiative and immunomodulatory effects. Breast Cancer Res Treat, 73, 61-73. https://doi.org/10.1023/A:1015272401822
  3. Bauer JA, Ye F, Marshall CB, et al (2010). RNA interference (RNAi) screening approach identifies agents that enhance paclitaxel activity in breast cancer cells. Breast Cancer Res, 12, 41.
  4. Branham MT, Nadin SB, Vargas-Roig LM, et al (2004). DNA damage induced by paclitaxel and DNA repair capability of peripheral blood lymphocytes as evaluated by the alkaline comet assay. Mutat Res, 560, 11-7. https://doi.org/10.1016/j.mrgentox.2004.01.013
  5. Bulavin DV, Demidov ON, Saito S, et al (2002). Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat Genet, 31, 210-5. https://doi.org/10.1038/ng894
  6. Burns TF, Fei P, Scata KA, et al (2003). Silencing of the novel p53 target gene Snk/Plk2 leads to mitotic catastrophe in paclitaxel (taxol)-exposed cells. Molec Cell Biol, 23, 5556-71. https://doi.org/10.1128/MCB.23.16.5556-5571.2003
  7. Cai X, Yu Y, Huang Y, et al (2003). Arsenic trioxide-induced mitotic arrest and apoptosis in acute promyelocytic leukemia cells. Leukemia, 17, 1333-7. https://doi.org/10.1038/sj.leu.2402983
  8. Cheng B, Yang X, Han Z, et al (2008). Arsenic trioxide induced the apoptosis of laryngeal cancer via down-regulation of survivin mRNA. Auris Nasus Larynx, 35, 95-101. https://doi.org/10.1016/j.anl.2007.07.009
  9. Chou TC, Talalay P (1984). Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul, 22, 27-55. https://doi.org/10.1016/0065-2571(84)90007-4
  10. Dogra S, Bandi S, Viswanathan P, et al (2015). Arsenic trioxide amplifies cisplatin toxicity in human tubular cells transformed by HPV-16 E6/E7 for further therapeutic directions in renal cell carcinoma. Cancer Lett, 356, 953-61. https://doi.org/10.1016/j.canlet.2014.11.008
  11. Duan XF, Wu YL, Xu HZ, et al (2010). Synergistic mitosisarresting effects of arsenic trioxide and paclitaxel on human malignant lymphocytes. Chem Biol Interact, 183, 222-30. https://doi.org/10.1016/j.cbi.2009.09.012
  12. Emadi A, Gore SD (2010). Arsenic trioxide-An old drug rediscovered. Blood Rev, 24, 191-9. https://doi.org/10.1016/j.blre.2010.04.001
  13. Fiscella M, Zhang H, Fan S, et al (1997). Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner. Proc Natl Acad Sci U S A, 94, 6048-53. https://doi.org/10.1073/pnas.94.12.6048
  14. Ghanbari P, Mohseni M, Tabasinezhad M, et al (2014). Inhibition of survivin restores the sensitivity of breast cancer cells to docetaxel and vinblastine. Appl Biochem Biotechnol.
  15. Goncalves A, Braguer D, Kamath K, et al (2001). Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics. Proc Natl Acad Sci U S A, 98, 11737-42. https://doi.org/10.1073/pnas.191388598
  16. Gottesman MM (2002). Mechanisms of cancer drug resistance. Annu Rev Med, 53, 615-27. https://doi.org/10.1146/annurev.med.53.082901.103929
  17. Halicka HD, Smolewski P, Darzynkiewicz Z, et al (2002). Arsenic trioxide arrests cells early in mitosis leading to apoptosis. Cell Cycle, 1, 201-9.
  18. Herbst RS, Khuri FR (2003). Mode of action of docetaxel-a basis for combination with novel anticancer agents. Cancer Treatment Reviews, 29, 407-15. https://doi.org/10.1016/S0305-7372(03)00097-5
  19. Ikui AE, Yang CP, Matsumoto T, et al (2005). Low concentrations of taxol cause mitotic delay followed by premature dissociation of p55CDC from Mad2 and BubR1 and abrogation of the spindle checkpoint, leading to aneuploidy. Cell Cycle, 4, 1385-8. https://doi.org/10.4161/cc.4.10.2061
  20. Kavallaris M (1997). The role of multidrug resistance-associated protein (MRP) expression in multidrug resistance. Anticancer Drugs, 8, 17-25. https://doi.org/10.1097/00001813-199701000-00002
  21. Kong W, Jiang X, Mercer WE (2009). Downregulation of Wip-1 phosphatase expression in MCF-7 breast cancer cells enhances doxorubicin-induced apoptosis through p53-mediated transcriptional activation of Bax. Cancer Biol Ther, 8, 555-63. https://doi.org/10.4161/cbt.8.6.7742
  22. Li Y, Qu X, Qu J, et al (2009). Arsenic trioxide induces apoptosis and G2/M phase arrest by inducing Cbl to inhibit PI3K/Akt signaling and thereby regulate p53 activation. Cancer Letters, 284, 208-15. https://doi.org/10.1016/j.canlet.2009.04.035
  23. Ling YH, Jiang JD, Holland JF, et al (2002). Arsenic trioxide produces polymerization of microtubules and mitotic arrest before apoptosis in human tumor cell lines. Mol Pharmacol, 62, 529-38. https://doi.org/10.1124/mol.62.3.529
  24. Liu H, Tao X, Ma F, et al (2012a). Radiosensitizing effects of arsenic trioxide on MCF-7 human breast cancer cells exposed to 89 strontium chloride. Oncol Rep, 28, 1894-902.
  25. Liu W, Gong Y, Li H, et al (2012b). Arsenic trioxide-induced growth arrest of breast cancer MCF-7 cells involving FOXO3a and IkappaB kinase beta expression and localization. Cancer Biother Radiopharm, 27, 504-12. https://doi.org/10.1089/cbr.2012.1162
  26. Lu X, Ma O, Nguyen TA, et al (2007). The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop. Cancer Cell, 12, 342-54. https://doi.org/10.1016/j.ccr.2007.08.033
  27. Lu X, Nannenga B, Donehower LA (2005). PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev, 19, 1162-74. https://doi.org/10.1101/gad.1291305
  28. Lu X, Nguyen TA, Moon SH, et al (2008). The type 2C phosphatase Wip1: an oncogenic regulator of tumor suppressor and DNA damage response pathways. Cancer Metastasis Rev, 27, 123-35. https://doi.org/10.1007/s10555-008-9127-x
  29. McGrogan BT, Gilmartin B, Carney DN, et al (2008). Taxanes, microtubules and chemoresistant breast cancer. Biochim Biophys Acta, 1785, 96-132.
  30. Melet A, Song K, Bucur O, et al (2008). Apoptotic pathways in tumor progression and therapy. Adv Exp Med Biol, 615, 47-79. https://doi.org/10.1007/978-1-4020-6554-5_4
  31. Meng XZ, Zheng TS, Chen X, et al (2011). microRNA expression alteration after arsenic trioxide treatment in HepG-2 cells. J Gastroenterol Hepatol, 26, 186-93. https://doi.org/10.1111/j.1440-1746.2010.06317.x
  32. Momand J, Jung D, Wilczynski S, et al (1998). The MDM2 gene amplification database. Nucleic Acids Res, 26, 3453-9. https://doi.org/10.1093/nar/26.15.3453
  33. Parssinen J, Alarmo EL, Karhu R, et al (2008). PPM1D silencing by RNA interference inhibits proliferation and induces apoptosis in breast cancer cell lines with wild-type p53. Cancer Genet Cytogenet, 182, 33-9. https://doi.org/10.1016/j.cancergencyto.2007.12.013
  34. Parssinen J, Kuukasjarvi T, Karhu R, et al (2007). High-level amplification at 17q23 leads to coordinated overexpression of multiple adjacent genes in breast cancer. Br J Cancer, 96, 1258-64. https://doi.org/10.1038/sj.bjc.6603692
  35. Platanias LC (2009). Biological responses to arsenic compounds. J Biol Chem, 284, 18583-7. https://doi.org/10.1074/jbc.R900003200
  36. Rivas MA, Venturutti L, Huang YW, et al (2012). Downregulation of the tumor-suppressor miR-16 via progestin-mediated oncogenic signaling contributes to breast cancer development. Breast Cancer Res, 14, 77. https://doi.org/10.1186/bcr3187
  37. Rossi M, Demidov ON, Anderson CW, et al (2008). Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites. Nucleic Acids Res, 36, 7168-80. https://doi.org/10.1093/nar/gkn888
  38. Sabzichi M, Hamishehkar H, Ramezani F, et al (2014). Luteolinloaded phytosomes sensitize human breast carcinoma MDAMB 231 cells to doxorubicin by suppressing Nrf2 mediated signalling. Asian Pac J Cancer Prev, 15, 5311-6. https://doi.org/10.7314/APJCP.2014.15.13.5311
  39. Samadi N, Bekele R, Capatos D, et al (2011). Regulation of lysophosphatidate signaling by autotaxin and lipid phosphate phosphatases with respect to tumor progression, angiogenesis, metastasis and chemo-resistance. Biochimie, 93, 61-70. https://doi.org/10.1016/j.biochi.2010.08.002
  40. Samadi N, Gaetano C, Goping IS, et al (2009). Autotaxin protects MCF-7 breast cancer and MDA-MB-435 melanoma cells against Taxol-induced apoptosis. Oncogene, 28, 1028-39. https://doi.org/10.1038/onc.2008.442
  41. Samadi N, Ghanbari P, Mohseni M, et al (2014). Combination therapy increases the efficacy of docetaxel, vinblastine and tamoxifen in cancer cells. J Cancer Res Ther, 10, 715-21.
  42. Sharifi S, Barar J, Hejazi MS, et al (2014). Roles of the Bcl-2/Bax Ratio, Caspase-8 and 9 in Resistance of Breast Cancer Cells to Paclitaxel. Asian Pac J Cancer Prev, 15, 8617-22. https://doi.org/10.7314/APJCP.2014.15.20.8617
  43. Siegel R, Naishadham D, Jemal A (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  44. Skidan I, Miao B, Thekkedath RV, et al (2009). In vitro cytotoxicity of novel pro-apoptotic agent DM-PIT-1 in PEGPE-based micelles alone and in combination with TRAIL. Drug Deliv, 16, 45-51. https://doi.org/10.1080/10717540802517951
  45. Takekawa M, Adachi M, Nakahata A, et al (2000). p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. Embo J, 19, 6517-26. https://doi.org/10.1093/emboj/19.23.6517
  46. Vousden KH, Lu X (2002). Live or let die: the cell's response to p53. Nat Rev Cancer, 2, 594-604. https://doi.org/10.1038/nrc864
  47. Wahl GM, Carr AM (2001). The evolution of diverse biological responses to DNA damage: insights from yeast and p53. Nat Cell Biol, 3, 277-86. https://doi.org/10.1038/ncb1201-e277
  48. Wang L, Mosel AJ, Oakley GG, et al (2012). Deficient DNA damage signaling leads to chemoresistance to cisplatin in oral cancer. Mol Cancer Ther, 11, 2401-9. https://doi.org/10.1158/1535-7163.MCT-12-0448
  49. Yoda A, Toyoshima K, Watanabe Y, et al (2008). Arsenic trioxide augments Chk2/p53-mediated apoptosis by inhibiting oncogenic Wip1 phosphatase. J Biol Chem, 283, 18969-79. https://doi.org/10.1074/jbc.M800560200
  50. Zekri A, Ghaffari SH, Yousefi M, et al (2013). Autocrine human growth hormone increases sensitivity of mammary carcinoma cell to arsenic trioxide-induced apoptosis. Mol Cell Endocrinol, 377, 84-92. https://doi.org/10.1016/j.mce.2013.07.002

피인용 문헌

  1. Development of a hybrid paclitaxel-loaded arsenite nanoparticle (HPAN) delivery system for synergistic combined therapy of paclitaxel-resistant cancer vol.19, pp.4, 2017, https://doi.org/10.1007/s11051-017-3848-0
  2. Arsenic trioxide inhibits cell growth and motility via up-regulation of let-7a in breast cancer cells pp.1551-4005, 2017, https://doi.org/10.1080/15384101.2017.1387699
  3. Trisenox induces cytotoxicity through phosphorylation of mitogen-activated protein kinase molecules in acute leukemia cells vol.32, pp.10, 2018, https://doi.org/10.1002/jbt.22207
  4. Targeted cancer drug delivery with aptamer-functionalized polymeric nanoparticles pp.1029-2330, 2018, https://doi.org/10.1080/1061186X.2018.1491978