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Thermodynamic behavior of breast cancer cell lines after miltefosine and cisplatin treatment

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Abstract

Breast cancers exhibit different response to drug treatment. In this work, we analyze and compare the effect of two anticancer drugs differing in their primary action, miltefosine and cisplatin (cis-Pt), on two different breast cancer (the low—(MCF-7) and high—(MDA-MB-231) metastatic) cell lines, and one normal epithelial (MCF-10A) breast cell lines. The effect of cip-Pt and miltefosine on the thermodynamic behavior of the cancer cell lines was analyzed by differential scanning calorimetry, the cell morphology and viability were determined by optical microscopy and MTT test. We revealed distinct effects of miltefosine and cis-Pt on the thermodynamic behavior and viability of the cancer and normal cells. Importantly, the normal MCF-10A cells were drastically affected by miltefosine, while not by cis-Pt. MDA-MB-231 cell line, on the other hand, is more susceptible to cis-Pt than MCF-7 cells, while both cancer cell lines are equally affected by miltefosine. The drug-associated alteration of the thermal unfolding of the cells constituents correlated with the changes in the cell viability. The altered thermodynamic behavior of the cancer cells upon the drug treatment strongly indicates altered conformations of the proteins in cancer cell membrane and cellular matrix, and the DNA-containing structures.

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References

  1. DeSantis CE, Ma J, Sauer AG, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67(6):439–48.

    Article  Google Scholar 

  2. Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Res. 2017;13:215. https://doi.org/10.1186/bcr2889.

    Article  Google Scholar 

  3. Dai X, Cheng H, Bai Zh, Li J. Breast cancer cell line classification and its relevance with breast tumor subtyping. J Cancer. 2017;8(16):3131–41.

    Article  Google Scholar 

  4. LaPorta E, Welsh JE. Modeling vitamin D actions in triple negative/basal-like breast cancer. J Steroid Biochem Mol Biol. 2014;144A:65–73.

    Article  Google Scholar 

  5. Hastak K, Alli E, Ford JM. Synergistic chemosensitivity of triple-negative breast cancer cell lines to poly(ADP-ribose) polymerase inhibition, gemcitabine, and cisplatin. Cancer Res. 2010;70:7970–80.

    Article  CAS  Google Scholar 

  6. Konstantinov S, Berger M. Human urinary bladder carcinoma cell lines respond to treatment with alkylphosphocholines. Cancer Lett. 1999;144(2):153–60.

    Article  CAS  Google Scholar 

  7. Berger MR, Tsoneva I, Konstantinov SM. Eibl H: Induction of apoptosis by erucylphospho-n, n, n-trimethylammonium is associated with changes in signal molecule expression and location. Ann N Y Acad Sci. 2003;1010:307–10.

    Article  CAS  Google Scholar 

  8. Fieg M, Juergens M, Hiddemann W, Braess J. Cytotoxic activity of the third-generation bisphosphonate zoledronic acid in acute myeloid leukemia. Leukemia Res. 2007;31(4):531–9.

    Article  Google Scholar 

  9. Pachioni J, Magalhães J, Lima EC, Bueno LM, Barbosa JF, de Sá MM, Rangel-Yagui CO. Alkylphospholipids: a promising class of chemotherapeutic agents with a broad pharmacological spectrum. J Pharm Pharm Sci. 2013;16(5):742–59.

    Article  Google Scholar 

  10. Soto J, Soto P. Miltefosine: oral treatment of leishmaniasis. Expert Rev Anti Infect Ther. 2006;4(2):177–85.

    Article  CAS  Google Scholar 

  11. Dorlo TPC, Balasegaram M, Beijnen JH, de Vries PJ. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012;67(11):2576–97.

    Article  CAS  Google Scholar 

  12. Dineva I, Zaharieva M, Konstantinov S, Eibl H, Berger MR. Erufosine suppresses breast cancer in vitro and in vivo for its activity on PI3K, c-Raf and Akt proteins. J Cancer Res Clinical Oncol. 2012;138:1909–17.

    Article  CAS  Google Scholar 

  13. Florea A, Busselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers. 2011;3:1351–71. https://doi.org/10.3390/cancers3011351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Dasari Sh, Tchounwou PB. Caisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;5:364–78.

    Article  Google Scholar 

  15. Nishiyama N, Okazak S, Cabral H, Miyamoto M, Kato Y, Sugiyama Y, Nishio K, Matsumura Y, Kataoka K. Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice. Cancer Res. 2003;63:8977–83.

    CAS  PubMed  Google Scholar 

  16. Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, Fatima A, Gelman RS, Ryan PD, Tung NM, De Nicolo A, Ganesan S, Miron A, Colin C, Sgroi DC, Ellisen LW, Winer EP, Garber JE. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol. 2010;28(7):1145–53.

    Article  CAS  Google Scholar 

  17. Prabhakaran P, Hassiotou F, Blancafort P, Filgueira L. Cisplatin induces differentiation of breast cancer cells. Front Oncol. 2013. https://doi.org/10.3389/fonc.2013.00134.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Siddic ZH. Cisplatin mode of cytotoxic action and molecular basis of resistance. Oncogene. 2003;22(47):7265–79.

    Article  Google Scholar 

  19. Basu A, Krishnamurthy S. Cellular responses to cisplatin-induced DNA damage. J Nucleic Acids. 2010. https://doi.org/10.4061/2010/201367.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Nicolini C. Chromatin structure: from nuclei to genes. Anticancer Res. 1983;3(2):63–86.

    CAS  PubMed  Google Scholar 

  21. Almagor M, Cole RD. Differential scanning calorimetry of nuclei as a test for the effects of anticancer drugs on human chromatin. Cancer Res. 1989;49(20):5561–6.

    CAS  PubMed  Google Scholar 

  22. Lepock JR, Frey HE, Heynen ML, Senisterra GA, Warters RL. The nuclear matrix is a thermolabile cellular structure. Cell Stress Chaperon. 2001;6(2):136–47.

    Article  CAS  Google Scholar 

  23. Todinova S, Stoyanova E, Krumova S, Iliev I, Taneva SG. Calorimetric signatures of human cancer cells and their nuclei. Thermochim Acta. 2016;623:95–101.

    Article  CAS  Google Scholar 

  24. Mossmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.

    Article  Google Scholar 

  25. Sambrook J, Russell DW. Molecular cloning: a laboratory manual. NewYork: Cold Spring Harbor Laboratory Press; 2001.

    Google Scholar 

  26. Davido T, Getzenberg RH. Nuclear matrix proteins as cancer markers. J Cell Biochem. 2000;35:136–41.

    Article  Google Scholar 

  27. Rynearson AL, Sussman CR. Nuclear structure, organization, and oncogenesis. J Gastroint Canc. 2011;42:112–7.

    Article  Google Scholar 

  28. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  CAS  Google Scholar 

  29. Zink D, Fischer AH, Nickerson JA. Nuclear structure in cancer cells. Nat Rev. 2004;4:677–87.

    Article  CAS  Google Scholar 

  30. True L, Jordan CD. The cancer nuclear microenvironment: Interface between light microscopic cytology and molecular phenotype. J Cell Biochem. 2008;104:1994–2003.

    Article  CAS  Google Scholar 

  31. Lombardi ML, Zwerger M, Lammerding J. Biophysical assays to probe the mechanical properties of the interphase cell nucleus: substrate strain application and microneedle manipulation. J Vis Exp. 2011;55(e3087):1–6.

    Google Scholar 

  32. Rybczynska M, Liu R, Lu P, Sharom FJ, Steinfels E, Di Pietro A, Spitaler M, Grunicke H, Hofmann J. MDR1 causes resistance to the antitumour drug Miltefosine-. Br J Cancer. 2001;84:1405–11.

    Article  CAS  Google Scholar 

  33. Barioni MB, Ramos AP, Zaniquelli MD, Acuna AU, Ito AS. Miltefozine and BODIPY-labeled alkylphosphocholine with leishmanicidalactivity: aggregation properties and characterization with model membranes. Biophys Chem. 2016;196:92–9.

    Article  Google Scholar 

  34. Yang M, Brackenbury WJ. Membrane potential and cancer progression. Front Phys. 2013;4:185. https://doi.org/10.3389/fphys.2013.00185.

    Article  CAS  Google Scholar 

  35. Petit K, Suwalsky M, Colina J, Aguilar L, Jemiola-Rzeminska M, Strzalka K. In vitro effects of antitumor drug miltefozine on human erythrocytes and molecular models of its membrane. BBA-Biomembr. 2019;1861:17–25.

    Article  CAS  Google Scholar 

  36. Liang Sh-Sh, Wang T-N, Tsai E-M. Analysis of protein–protein interactions in mcf-7 and mda-mb-231 cell lines using phthalic acid chemical. Int J Mol Sci. 2014;15:20770–88.

    Article  CAS  Google Scholar 

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Acknowledgements

This research was partly supported by COST COMULIS CA17121.

Funding

This work was supported by a grant from the National Science Fund of Bulgaria (Grant KP-05-COST/10 to B.N.) and by grant D01-392/2020 “National Center for Biomedical Photonics”, part of Bulgarian National Roadmap for Scientific Infrastructures 2020–2027, supported by Bulgarian Ministry of Education and Science.

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Correspondence to Stefka G. Taneva.

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Todinova, S., Nikolova, B., Iliev, I. et al. Thermodynamic behavior of breast cancer cell lines after miltefosine and cisplatin treatment. J Therm Anal Calorim 147, 7819–7828 (2022). https://doi.org/10.1007/s10973-021-11094-6

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  • DOI: https://doi.org/10.1007/s10973-021-11094-6

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