Asian Pacific Journal of Cancer Prevention

  • 제17권7호
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  • Pages.3223-3228
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  • 2016
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  • 1513-7368(pISSN)
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  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
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15d-PGJ2 Induces Apoptosis of MCF-7 and MDA-MB-231 Cells via Increased Intracellular Calcium and Activation of Caspases, Independent of ERα and ERβ

  • Muhammad, Siti Nur Hasyila (Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus) ;
  • Mokhtar, Noor Fatmawati (nstitute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Health Campus) ;
  • Yaacob, Nik Soriani (Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus)
  • 발행 : 2016.07.01
⟨ 이전 논문 다음 논문 ⟩

초록

Reports indicate that 15-deoxy-delta-12,14-prostaglandin-J2 (15d-PGJ2) has anticancer activities, but its mechanisms of action have yet to be fully elucidated. We therefore investigated the effects of 15d-PGJ2 on the human breast cancer cell lines, MCF-7 (estrogen receptor $ER{\alpha}+/ER{\beta}+$) and MDA-MB-231 ($ER{\alpha}-/ER{\beta}+$). Cellular proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays while apoptosis was determined by fluorescence microscopy and flow cytometry using annexin V-propidium iodide (PI) staining. ER expression was determined by Western blotting. Intracellular calcium was stained with Fluo-4 AM while intracellular caspase activities were detected with Caspase-$FLICA(R)$ and measured by flow cytometry. We showed that 15d-PGJ2 caused a significant increase in apoptosis in MCF-7 and MDA-MB-231 cells. $ER{\alpha}$ protein expression was reduced in treated MCF-7 cells but pre-incubation with the $ER{\alpha}$ inhibitor' ICI 182 780' did not affect the percentage of apoptotic cells. The expression of $ER{\beta}$ was unchanged in both cell lines. In addition, 15d-PGJ2 increased intracellular calcium ($Ca^{2+}$) staining and caspase 8, 9 and 3/7 activities. We therefore conclude that 15d-PGJ2 induces caspase-dependent apoptosis that is associated with an influx of intracellular $Ca^{2+}$ with no involvement of ER signaling.

키워드

과제정보

연구 과제 주관 기관 : Ministry of Science Technology and Innovation

참고문헌

  1. Chaffer CL, Thomas DM, Thompson EW, et al (2006). PPARgamma-independent induction of growth arrest and apoptosis in prostate and bladder carcinoma. BMC Cancer, 6, 53. https://doi.org/10.1186/1471-2407-6-53
  2. Chen Y, Li Z, He Y, et al (2014). Estrogen and pure antiestrogen fulvestrant (ICI 182 780) augment cell-matrigel adhesion of MCF-7 breast cancer cells through a 14 novel G protein coupled estrogen receptor (GPR30)-to-calpain signaling axis. Toxicol Appl Pharmacol, 275, 176-81. https://doi.org/10.1016/j.taap.2014.01.005
  3. Cho WH, Choi CH, Park JY, et al (2006). 15-deoxy-(Delta12,14)-prostaglandin J2 (15d-PGJ2) induces cell death through caspase-independent mechanism in A172 human glioma cells. Neurochem Res, 31, 1247-54. https://doi.org/10.1007/s11064-006-9157-0
  4. Ciucci A, Gianferretti P, Piva R, et al (2006). Induction of apoptosis in estrogen receptor-negative breast cancer cells by natural and synthetic cyclopentenones: role of the IkappaB kinase/nuclear factor-kappaB pathway. Mol Pharmacol, 70, 1812-21. https://doi.org/10.1124/mol.106.025759
  5. Croasdell A, Duffney PF, Kim N, et al (2015). $PPAR{\gamma}$ and the innate immune system mediate the resolution of inflammation. PPAR Res, 2015, 549691.
  6. Decuypere J-P, Monaco G, Bultynck G, et al (2011). The IP3 receptor-mitochondria connection in apoptosis and autophagy. Biochimica et Biophysica Acta, 1813, 1003-13. https://doi.org/10.1016/j.bbamcr.2010.11.023
  7. Dejeana LM, Martinez-Caballeroa S, Manonb S, et al (2006). Regulation of the mitochondrial apoptosis-induced channel, MAC, by BCL-2 family proteins. Biochimica et Biophysica Acta, 1762, 191-201. https://doi.org/10.1016/j.bbadis.2005.07.002
  8. Dionne S, Levy E, Levesque D, et al (2010). PPARgamma ligand 15-deoxy-delta 12,14-prostaglandin J2 sensitizes human colon carcinoma cells to TWEAK-induced apoptosis. Anticancer Res, 30, 157-66
  9. Egger J, Fischer S, Bretscher P, et al (2015). Total synthesis of prostaglandin 15d- PGJ2 and investigation of its effect on the secretion of IL-6 and IL-12. Org. Lett, 17, 4340-3. https://doi.org/10.1021/acs.orglett.5b02181
  10. Fujita M, Tohji C, Honda Y, et al (2012). Cytotoxicity of 15-deoxy-Delta(12,14)- prostaglandin J(2) through PPARgamma-independent pathway and the involvement of the JNK and Akt pathway in renal cell carcinoma. Int J Med Sci, 9, 555-66. https://doi.org/10.7150/ijms.4455
  11. Jo DG, Jun JI, Chang JW, et al (2004). Calcium binding of ARC mediates regulation of caspase 8 and cell death. Mol Cell Biol, 24, 9763-70. https://doi.org/10.1128/MCB.24.22.9763-9770.2004
  12. Kim EJ, Park KS, Chung SY, et al (2003). Peroxisome proliferator-activated receptor-gamma activator 15-deoxy-Delta12,14-prostaglandin J2 inhibits neuroblastoma cell growth through induction of apoptosis: association with extracellular signal-regulated kinase signal pathway. J Pharmacol Exp Ther, 307, 505-17. https://doi.org/10.1124/jpet.103.053876
  13. Kim HJ, Kim JY, Meng Z, et al (2007). 15-deoxy-Delta12,14-prostaglandin J2 inhibits transcriptional activity of estrogen receptor-alpha via covalent modification of DNA-binding domain. Cancer Res, 67, 2595-602. https://doi.org/10.1158/0008-5472.CAN-06-3043
  14. Kim JH, Song J, Park KW (2015). The multifaceted factor peroxisome proliferator- activated receptor ${\gamma}$ ($PPAR{\gamma}$) in metabolism, immunity, and cancer. Arch Pharm Res, 38, 302-12. https://doi.org/10.1007/s12272-015-0559-x
  15. Kocanova S, Mazaheri M, Caze-Subra S, et al (2010). Ligands specify estrogen receptor alpha nuclear localization and degradation. BMC Cell Biol, 11, 98. https://doi.org/10.1186/1471-2121-11-98
  16. Landar A, Shiva S, Levonen AL, et al (2006). Induction of the permeability transition and cytochrome c release by 15-deoxy-Delta12,14-prostaglandin J2 in mitochondria. Biochem J, 394, 185-95. https://doi.org/10.1042/BJ20051259
  17. Lecomte J, Flament S, Salamone S, et al (2008). Disruption of ERalpha signalling pathway by PPARgamma agonists: evidences of PPARgamma-independent events in two hormone-dependent breast cancer cell lines. Breast Cancer Res Treat, 112, 437-51. https://doi.org/10.1007/s10549-007-9886-z
  18. Li H, Pauza CD (2009). Effects of 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) and rosiglitazone on human gammadelta2 T cells. PLoS One, 4, 7726. https://doi.org/10.1371/journal.pone.0007726
  19. McKeage K, Curran MP, Plosker GL (2004). Fulvestrant: a review of its use in hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy. Drugs, 64, 633-8. https://doi.org/10.2165/00003495-200464060-00009
  20. Monteith GR, Mcandrew D, Faddy HM, et al (2007). Calcium and cancer: targeting $Ca^{2+}$ transport. Nat Rev Cancer, 7, 519-30. https://doi.org/10.1038/nrc2171
  21. Mughal A, Kumar D, Vikram A (2015). Effects of Thiazolidinediones on metabolism and cancer: Relative influence of $PPAR{\gamma}$ and IGF-1 signaling. Eur J Pharmacol, 768, 217-25. https://doi.org/10.1016/j.ejphar.2015.10.057
  22. Napimoga MH, Demasib APD, Bossonarob JP et al (2013). Low doses of 15d-PGJ2 induce osteoblast activity in a PPAR-gamma independent manner. International Immunopharmacol, 16, 131-8. https://doi.org/10.1016/j.intimp.2013.03.035
  23. Orrenius S, Zhivotovsky B, Nicotera P (2003). Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol, 4, 552-65. https://doi.org/10.1038/nrm1150
  24. Pacher P, Hajnoczky G (2001). Propagation of the apoptotic signal by mitochondrial waves. EMBO J, 20, 4107-21. https://doi.org/10.1093/emboj/20.15.4107
  25. Parrish AB, Freel CD and Kornbluth S (2013). Cellular Mechanisms Controlling Caspase Activation and Function Cold Spring Harb Perspect Biol, 5, 8672. https://doi.org/10.1101/cshperspect.a008672
  26. Popolo A, Piccinelli AL, Morello S, et al (2011). Cytotoxic activity of nemorosone in human MCF-7 breast cancer cells. Can J Physiol Pharmacol, 89, 50-7. https://doi.org/10.1139/Y10-100
  27. Qin C, Burghardt R, Smith R, et al (2003). Peroxisome proliferator-activated receptor gamma agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor alpha in MCF-7 breast cancer cells. Cancer Res, 63, 958-64.
  28. Rao GK, Zhang W, Kaminski NE (2004). Cannabinoid receptormediated regulation of intracellular calcium by delta(9)-tetrahydrocannabinol in resting T cells. J Leukoc Biol, 75, 884-92. https://doi.org/10.1189/jlb.1203638
  29. Rizzuto R, Pinton P, Ferrari D, et al (2003). Calcium and apoptosis: facts and hypotheses. Oncogene, 22, 8619-27. https://doi.org/10.1038/sj.onc.1207105
  30. Shin SW, Seo CY, Han H, et al (2009). 15d-PGJ2 induces apoptosis by reactive oxygen species-mediated inactivation of Akt in leukemia and colorectal cancer cells and shows in vivo antitumor activity. Clin Cancer Res, 15, 5414-25. https://doi.org/10.1158/1078-0432.CCR-08-3101
  31. Twiddy D, Cohen GM, Macfarlane M, et al (2006). Caspase-7 is directly activated by the approximately 700-kDa apoptosome complex and is released as a stable XIAPcaspase-7 approximately 200-kDa complex. J Biol Chem, 281, 3876-88. https://doi.org/10.1074/jbc.M507393200
  32. Wen J, Huang YC, Xiu HH, et al (2016). Altered expression of stromal interaction molecule (STIM)-calcium releaseactivated calcium channel protein (ORAI) and inositol 1,4,5-trisphosphate receptors (IP3Rs) in cancer: will they become a new battlefield for oncotherapy? Chin J Cancer, 35, 32. https://doi.org/10.1186/s40880-016-0094-2
  33. Yaacob NS, Nasir R, Norazmi MN (2013). Influence of 17betaestradiol on 15- deoxy-delta12,14 prostaglandin J2 -induced apoptosis in MCF-7 and MDA-MB-231 cells. Asian Pac J Cancer Prev, 14, 6761-7. https://doi.org/10.7314/APJCP.2013.14.11.6761
  34. Yen CC, Hsiao CD, Chen WM, et al. (2014). Cytotoxic effects of 15d-PGJ2 against osteosarcoma through ROS-mediated AKT and cell cycle inhibition. Oncotarget, 5, 716-25. https://doi.org/10.18632/oncotarget.1704
  35. Yu K, He Y, Yeung LW, et al (2008). DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondriacaspase protease pathway in human neuroblastoma cells in vitro. Toxicol Sci, 104, 341-51. https://doi.org/10.1093/toxsci/kfn088
  36. Zingarelli B, Sheehan M, Hake PW, et al (2003). Peroxisome proliferator activator receptor-gamma ligands, 15-deoxy-Delta (12,14)-prostaglandin J2 and ciglitazone, reduce systemic inflammation in polymicrobial sepsis by modulation of signal transduction pathways. J Immunol, 171, 6827-37. https://doi.org/10.4049/jimmunol.171.12.6827
  37. Zoli W, Ulivi P, Tesei A. et al (2005). Addition of 5-fluorouracil to doxorubicin- paclitaxel sequence increases caspasedependent apoptosis in breast cancer cell lines. Breast Cancer Res, 7, 681-9. https://doi.org/10.1186/bcr1274