Comparative proteomics study of proteins involved in induction of higher rates of cell death in mitoxantrone-resistant breast cancer cells MCF-7/MX exposed to TNF-α

Document Type: Original Article

Authors

1 Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 Molecular and Cell Biology Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3 Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran

4 Department of Pharmacognosy and Pharmaceutical Biotechnology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

5 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

6 School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada

7 Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): Resistance to medications is one of the main complications in chemotherapy of cancer. It has been shown that some multidrug resistant cancer cells indicate more sensitivity against cytotoxic effects of TNF-α compared to their parental cells. Our previous findings indicated vulnerability of the mitoxantrone-resistant breast cancer cells MCF-7/MX to cell death induced by TNF-α compared to the parent cells MCF-7. In this study, we performed a comparative proteomics analysis for identification of proteins involved in induction of higher susceptibility of MCF-7/MX cells to cytotoxic effect of TNF-α.
Materials and Methods: Intensity of protein spots in 2D gel electrophoresis profiles of MCF-7 and MCF-7/MX cells were compared with Image Master Platinum 6.0 software. Selected differential protein-spots were identified with MALDI-TOF/TOF mass spectrometry and database searching. Pathway analyses of identified proteins were performed using PANTHER, KEGG PATHWAY, Gene MANIA and STRING databases. Western blot was performed for confirmation of the proteomics results.
Results: Our results indicated that 48 hr exposure to TNF-α induced 87% death in MCF-7/MX cells compared to 19% death in MCF-7 cells. Forty landmarks per 2D gel electrophoresis were matched by Image Master Software. Six proteins were identified with mass spectrometry. Western blot showed that 14-3-3γ and p53 proteins were expressed higher in MCF-7/MX cells treated with TNF-α compared to MCF-7 cells treated with TNF-α.
Conclusion: Our results showed that 14-3-3 γ, prohibitin, peroxiredoxin 2 and P53 proteins which were expressed differentially in MCF-7/MX cells treated with TNF-α may involve in the induction of higher rates of cell death in these cells compared to TNF-α-treated MCF-7 cells.

Keywords


1. Farzad N, Barati N, Momtazi-Borojeni AA, Yazdani M, Arab A, Razazan A, et al. P435 HER2/neu-derived peptide conjugated to liposomes containing DOPE as an effective prophylactic vaccine formulation for breast cancer. Artif Cells Nanomed Biotechnol. 2019;47:665-673.
2. Choi C-H. ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int. 2005;5:30.
3. Gillet J-P, Gottesman MM. Mechanisms of multidrug resistance in cancer.  Methods Mol Biol. 2010;596:47-76.
4. Pluchino KM, Hall MD, Goldsborough AS, Callaghan R, Gottesman MM. Collateral sensitivity as a strategy against cancer multidrug resistance. Drug Resist Updat. 2012;15:98-105.
5. Arab A, Behravan N, Razazn A, Barati N, Mosaffa F, Nicastro J, et al. The viral approach to breast cancer immunotherapy. J Cell Physiol. 2019;234:1257-1267.
6. Behravan J, Razazan A, Behravan G. Towards Breast Cancer Vaccines, Progress and Challenges. Curr Drug Discov Technol. 2019;16:251-258.
7. Zhou L, Wang H, Li Y. Stimuli-responsive nanomedicines for overcoming cancer multidrug resistance. Theranostics. 2018;8:1059.
8. Barati N, Razazan A, Nicastro J, Slavcev R, Arab A, Mosaffa F, et al. Immunogenicity and antitumor activity of the superlytic λF7 phage nanoparticles displaying a HER2/neu-derived peptide AE37 in a tumor model of BALB/c mice. Cancer lett. 2018;424:109-116.
9. Razazan A, Behravan J, Arab A, Barati N, Arabi L, Gholizadeh Z, et al. Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model. PloS one. 2017;12:e0185099.
10. Razazan A, Nicastro J, Slavcev R, Barati N, Arab A, Mosaffa F, et al. Lambda bacteriophage nanoparticles displaying GP2, a HER2/neu derived peptide, induce prophylactic and therapeutic activities against TUBO tumor model in mice. Sci Rep. 2019;9:2221.
11. Mosaffa F, Lage H, Afshari JT, Behravan J. Interleukin-1 beta and tumor necrosis factor-alpha increase ABCG2 expression in MCF-7 breast carcinoma cell line and its mitoxantrone-resistant derivative, MCF-7/MX. Inflamm Res. 2009;58:669-676.
12. Duffy M. The war on cancer: are we winning? Tumor Biology. 2013;34:1275-1284.
13. Giménez-Bonafé P, Tortosa A, Pérez-Tomás R. Overcoming drug resistance by enhancing apoptosis of tumor cells. Curr Cancer Drug Targets. 2009;9:320-340.
14. Ramalhete C, Mulhovo S, Lage H, Ferreira M-JU. Triterpenoids from momordica balsamina with a collateral sensitivity effect for tackling multidrug resistance in cancer cells. Planta med. 2018;84:1372-1379..
15. Klukovits A, Krajcsi P. Mechanisms and therapeutic potential of inhibiting drug efflux transporters. Expert Opin Drug Metab Toxicol. 2015;11:907-920.
16. Borsellino N, Crescimanno M, Flandina C, Flugy A, D’Alessandro N. Combined activity of interleukin-1 alpha or TNF-alpha and doxorubicin on multidrug resistant cell lines: evidence that TNF and DXR have synergistic antitumor and differentiation-inducing effects. Anticancer Res. 1994;14:2643-2648.
17. Cenni V, Maraldi NM, Ruggeri A, Secchiero P, Del Coco R, De Pol A, et al. Sensitization of multidrug resistant human ostesarcoma cells to Apo2 Ligand/TRAIL-induced apoptosis by inhibition of the Akt/PKB kinase. Int J Oncol.2004;25:1599-1608.
18. D’Alessandro N, Flugy A, Tolomeo M, Dusonchet L. The apoptotic signaling of TNF-alpha in multidrug resistant Friend leukemia cells. Anticancer Res. 1998;18:3065-3072.
19. Flugy A, Borsellino N, D’Alessandro N. TNF-induced apoptosis in multidrug resistant friend erythroleukemia is not influenced by the P-glycoprotein and glutathione status of the cell line. Oncol Res. 1995;7:559-564.
20. Wang Y, Wen S, Wang F, Wen L, Yang B, Yang J, et al. Apoptosis of the adriamycin-resistant leukemia cell line induced by the recombinant mutant human TNF-related apoptosis-inducing ligand combined with arsenic trioxide. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16:1055-1059.
21. Ghandadi M, Behravan J, Abnous K, Gharaee ME, Mosaffa F. TNF-α exerts cytotoxic effects on multidrug resistant breast cancer MCF-7/MX cells via a non-apoptotic death pathway. Cytokine. 2017;97:167-174.
22. Ghandadi M, Haj-Ali N, Behravan J, Abnous K, Mohammadi A, Gharaee ME, et al. TNF-α exerts higher cytotoxic effect on MCF-7 multidrug resistant derivative, role of Akt activation. Breast Dis. 2015;35:241-247.
23. Yazdian–Robati R, Ahmadi H, Riahi MM, Lari P, Aledavood SA, Rashedinia M, et al. Comparative proteome analysis of human esophageal cancer and adjacent normal tissues. Iran J Basic Med Sci. 2017;20:265.
24. Hassani FV, Abnous K, Mehri S, Jafarian A, Birner-Gruenberger R, Robati RY, et al. Proteomics and phosphoproteomics analysis of liver in male rats exposed to bisphenol A: Mechanism of hepatotoxicity and biomarker discovery. Food Chem Toxicol. 2018;112:26-38.
25. Kowsari R, Yazdian-Robati R, Razavi BM, Pourtaji A, Ghorbani M, Moghadam-Omranipour H, et al. Recognition and characterization of Erythropoietin binding-proteins in the brain of mice. Iran J Basic Med Sci. 2016;19:946.
26. Taghavi S, HashemNia A, Mosaffa F, Askarian S, Abnous K, Ramezani M. Preparation and evaluation of polyethylenimine-functionalized carbon nanotubes tagged with 5TR1 aptamer for targeted delivery of Bcl-xL shRNA into breast cancer cells. Colloids Surf B Biointerfaces. 2016;140:28-39.
27. Shen Q, Hu X, Zhou L, Zou S, Sun L-Z, Zhu X. Overexpression of the 14-3-3γ protein in uterine leiomyoma cells results in growth retardation and increased apoptosis. Cell Signal. 2018;45:43-53.
28. Parmiani G, Rivoltini L, Andreola G, Carrabba M. Cytokines in cancer therapy. Immunol Lett. 2000;74:41-44.
29. Josephs SF, Ichim TE, Prince SM, Kesari S, Marincola FM, Escobedo AR, et al. Unleashing endogenous TNF-alpha as a cancer immunotherapeutic. J Transl Med. 2018;16:242.
30. Mocellin S, Rossi CR, Pilati P, Nitti D. Tumor necrosis factor, cancer and anticancer therapy. Cytokine Growth Factor Rev. 2005;16:35-53.
31. Grünhagen DJ, Brunstein F, Graveland WJ, van Geel AN, de Wilt JH, Eggermont AM. One hundred consecutive isolated limb perfusions with TNF-α and melphalan in melanoma patients with multiple in-transit metastases. Ann Surg. 2004;240:939.
32. Wu X, Wu M-Y, Jiang M, Zhi Q, Bian X, Xu M-D, et al. TNF-α sensitizes chemotherapy and radiotherapy against breast cancer cells. Cancer Cell Int. 2017;17:13.
33. Radeff-Huang J, Seasholtz TM, Chang JW, Smith JM, Walsh CT, Brown JH. Tumor necrosis factor-α-stimulated cell proliferation is mediated through sphingosine kinase-dependent Akt activation and cyclin D expression. J Biol Chem. 2007;282:863-870.
34. Efferth T, Saeed ME, Kadioglu O, Seo E-J, Shirooie S, Mbaveng AT, et al. Collateral sensitivity of natural products in drug-resistant cancer cells. Biotechnol Adv.2019.
35. Aitken A, editor 14-3-3 proteins: a historic overview. Semin Cancer Biol. 2006;16:162-172.
36. Morrison DK. The 14-3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development. Trends Cell Biol. 2009;19:16-23.
37. Zhang R, Zhang H, Lin Y, Li J, Pober JS, Min W. RIP1-mediated AIP1 phosphorylation at a 14-3-3-binding site is critical for tumor necrosis factor-induced ASK1-JNK/p38 activation. J Biol Chem. 2007;282:14788-14796.
38. Hosing AS, Kundu ST, Dalal SN. 14-3-3 Gamma is required to enforce both the incomplete S phase and G2 DNA damage checkpoints. Cell Cycle. 2008;7:3171-3179.
39. Jin Y, Dai MS, Lu SZ, Xu Y, Luo Z, Zhao Y, et al. 14‐3‐3γ binds to MDMX that is phosphorylated by UV‐activated Chk1, resulting in p53 activation. EMBO J. 2006;25:1207-1218.
40. Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS lett. 1997;420:25-27.
41. Sharp DA, Kratowicz SA, Sank MJ, George DL. Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein. J Biol Chem. 1999;274:38189-38196.
42. Shvarts A, Steegenga W, Riteco N, Laar Tv, Dekker P, Bazuine M, et al. MDMX: a novel p53‐binding protein with some functional properties of MDM2. EMBO J. 1996;15:5349-5357.
43. Sime W, Niu Q, Abassi Y, Masoumi KC, Zarrizi R, Køhler JB, et al. BAP1 induces cell death via interaction with 14-3-3 in neuroblastoma. Cell Death Dis.2018;9:458.
44. Du J, Liao W, Wang Y, Han C, Zhang Y. Inhibitory effect of 14-3-3 proteins on serum-induced proliferation of cardiac fibroblasts. Eur J Cell Biol. 2005;84:843-852.
45. Chu N, Salguero AL, Liu AZ, Chen Z, Dempsey DR, Ficarro SB, et al. Akt kinase activation mechanisms revealed using protein semisynthesis. Cell. 2018;174:897-907.
46. Manning BD, Toker A. AKT/PKB signaling: navigating the network. Cell. 2017;169:381-405.
47. Zhang X, Tang N, Hadden TJ, Rishi AK. Akt, FoxO and regulation of apoptosis. Biochim Biophys Acta.2011;1813:1978-1986.
48. Nakae J, Kitamura T, Silver DL, Accili D. The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest. 2001;108:1359-1367.
49. Ranjan A, Iwakuma T. Non-Canonical Cell Death Induced by p53. Int J Mol Sci. 2016;17:2068.
50. Tu H-C, Ren D, Wang GX, Chen DY, Westergard TD, Kim H, et al. The p53-cathepsin axis cooperates with ROS to activate programmed necrotic death upon DNA damage. Proc Natl Acad Sci U S A. 2009;106:1093.
51. Marchenko ND, Moll UM. Mitochondrial death functions of p53. Mol Cell Oncol. 2014;1:e955995-e.
52. Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell. 2012;149:1536-1548.
53. Montero J, Dutta C, van Bodegom D, Weinstock D, Letai A. p53 regulates a non-apoptotic death induced by ROS. Cell Death Differ. 2013;20:1465-1474.
54. Wang K, Liu F, Liu CY, An T, Zhang J, Zhou LY, et al. The long noncoding RNA NRF regulates programmed necrosis and myocardial injury during ischemia and reperfusion by targeting miR-873. Cell Death Differ. 2016;23:1394-1405.
55. Peng Y-T, Chen P, Ouyang R-Y, Song L. Multifaceted role of prohibitin in cell survival and apoptosis. Apoptosis. 2015;20:1135-1149.
56. Peng X, Mehta R, Wang S, Chellappan S, Mehta RG. Prohibitin is a novel target gene of vitamin D involved in its antiproliferative action in breast cancer cells. Cancer Res. 2006;66:7361-7369.
57. Zhu B, Zhai J, Zhu H, Kyprianou N. Prohibitin regulates TGF‐β induced apoptosis as a downstream effector of smad‐dependent and‐independent signaling. Prostate.2010;70:17-26.
58. Fusaro G, Dasgupta P, Rastogi S, Joshi B, Chellappan S. Prohibitin induces the transcriptional activity of p53 and is exported from the nucleus upon apoptotic signaling. J Biol Chem. 2003;278:47853-47861.
59. Ghandadi M, Behravan J, Abnous K, Mosaffa F. Reactive Oxygen Species Mediate TNF-⍺ Cytotoxic Effects in the Multidrug-Resistant Breast Cancer Cell Line MCF-7/MX. Oncol Res Treat.  2016;39:54-59.