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Protocols for the Study of Taxanes Chemosensitivity in Prostate Cancer

  • M. Luz Flores
  • Carmen SáezEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1786)

Abstract

Prostate cancer is major cause of cancer-related death among men in Western countries. Locally advanced prostate cancers are treated with castration therapy, which is initially effective, but after months the disease progresses to a hormone-refractory state whose treatment is chemotherapy based on taxanes. Although taxanes improve the survival of patients with castration-resistant prostate cancers, these patients often develop chemotherapy resistance, and new therapeutic strategies are necessary. Taxanes exert their action through interaction with β-tubulin which triggers cell cycle arrest in mitosis and the subsequent induction of the intrinsic apoptotic pathway. Since taxanes are widely used for the treatment of advanced prostate cancers, we present in this chapter protocols that allow the study of the prostate cancer sensitivity as well as determine the mechanisms of resistance to these chemotherapeutic agents.

Key words

Prostate cancer Taxanes chemosensitivity Apoptosis Spindle assembly checkpoint Mitotic arrest Slippage 

Notes

Acknowledgments

This work was supported by research grants from the Instituto de Salud Carlos III (FIS PI13/2282; FIS PI17/1240), and Consejería de Innovación, Ciencia y Empresa (P10-CTS-6243), Junta de Andalucía. CS was supported by a contract from Nicolás Monardes Program, Consejería de Salud, Junta de Andalucía.

References

  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN. Int J Cancer 136(5):E359–E386CrossRefGoogle Scholar
  2. 2.
    Behnsawy HM, Miyake H, Harada K, Fujisawa M (2013) Expression patterns of epithelial-mesenchymal transition markers in localized prostate cancer: significance in clinicopathological outcomes following radical prostatectomy. BJU Int 111:30–37CrossRefPubMedGoogle Scholar
  3. 3.
    Sarkar S, Das S (2016) A review of imaging methods for prostate cancer detection. Biomed Eng Comput Biol 7(Suppl 1):1–15PubMedCentralPubMedGoogle Scholar
  4. 4.
    Gleason DF, Mellinger GT (1974) Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. J Urol 111(1):58–64CrossRefPubMedGoogle Scholar
  5. 5.
    Uzgare AR, Isaacs JT (2005) Prostate cancer: potential targets of anti-proliferative and apoptotic signaling pathways. Int J Biochem Cell Biol 37(4):707–714CrossRefPubMedGoogle Scholar
  6. 6.
    Shen MM, Abate-Shen C (2010) Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev 24(18):1967–2000CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Pound CR, Partin AW, Epstein JI, Walsh PC (1997) Prostate-specific antigen after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control. Urol Clin North Am 24(2):395–406CrossRefPubMedGoogle Scholar
  8. 8.
    Nilsson S, Norlen BJ, Widmarks A (2004) A systematic overview of radiation therapy effects in prostate cancer. Acta Oncol 43(4):316–381CrossRefPubMedGoogle Scholar
  9. 9.
    Bruckheimer EM, Kyprianou N (2000) Apoptosis in prostate carcinogenesis. A growth regulator and a therapeutic target. Cell Tissue Res 301(1):153–162CrossRefPubMedGoogle Scholar
  10. 10.
    Abate-Shen C, Shen MM (2000) Molecular genetics of prostate cancer. Genes Dev 14(19):2410–2434CrossRefPubMedGoogle Scholar
  11. 11.
    Chi K, Hotte SJ, Joshua AM, North S, Wyatt AW, Collins LL, Saad F (2015) Treatment of mCRPC in the AR-axis-targeted therapy-resistant state. Ann Oncol 26:2044–2056CrossRefPubMedGoogle Scholar
  12. 12.
    Chi KN, Bjartell A, Dearnaley D, Saad F, Schröder FH, Sterngerg C, Tombal B, Visakorpi T (2009) Castration-resistant prostate cancer: from new pathophysiology to new treatment targets. Eur Urol 56(4):594–605CrossRefPubMedGoogle Scholar
  13. 13.
    Bhalla KN (2003) Microtubule-targeted anticancer agents and apoptosis. Oncogene 22(56):9075–9086CrossRefPubMedGoogle Scholar
  14. 14.
    Gascoigne KE, Taylor SS (2008) Cancer cells display profound intra- and interline variation following prolonged exposure to antimitotic drugs. Cancer Cell 14(2):111–122CrossRefPubMedGoogle Scholar
  15. 15.
    van Delft MF, Huang DC (2006) How the Bcl-2 family of proteins interact to regulate apoptosis. Cell Res 16(2):203–213CrossRefPubMedGoogle Scholar
  16. 16.
    Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8(5):379–393CrossRefPubMedGoogle Scholar
  17. 17.
    Ciliberto A, Shah JV (2009) A quantitative systems view of the spindle assembly checkpoint. EMBO J 28(15):2162–2173CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Matsuyoshi S, Shimada K, Nakamura M, Ishida E, Konishi N (2006) Bcl-2 phosphorylation has pathological significance in human breast cancer. Pathobiology 73(4):205–212CrossRefPubMedGoogle Scholar
  19. 19.
    Basu A, DuBois G, Haldar S (2006) Posttranslational modifications of Bcl2 family members–a potential therapeutic target for human malignancy. Front Biosci 11(1):1508–1521CrossRefPubMedGoogle Scholar
  20. 20.
    Zhu Y, Zhou Y, Shi J (2014) Post-slippage multinucleation renders cytotoxic variation in anti-mitotic drugs that target microtubules or mitotic spindle. Cell Cycle 13:1756–1764CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Brito DA, Rieder CL (2006) Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. Curr Biol 16(12):1194–1200CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Rieder CL, Maiato H (2004) Stuck in division or passing through: what happens when cells cannot satisfy the spindle assembly checkpoint. Dev Cell 7(5):637–651CrossRefPubMedGoogle Scholar
  23. 23.
    Gascoigne KE, Taylor SS (2009) How do anti-mitotic drugs kill cancer cells? J Cell Sci 122(Pt15):2579–2585CrossRefPubMedGoogle Scholar
  24. 24.
    Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wideranging implications in tissue kinetics. Br J Cancer 26(4):239–257CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kerr JF, Winterford CM, Harmon BV (1994) Apoptosis. Its significance in cancer and cancer therapy. Cancer 73(8):2013–2026CrossRefPubMedGoogle Scholar
  26. 26.
    Um HD (2015) Bcl-2 family proteins as regulators of cancer cell invasion and metastasis: a review focusing on mitochondrial respiration and reactive oxygen species. Oncotarget 7(5):5193–5203PubMedCentralPubMedGoogle Scholar
  27. 27.
    Chipuk JE, Moldoveanu T, Llambi F, Parsons MJ, Green DR (2010) The BCL-2 family reunion. Mol Cell 37(3):299–310CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Kollek M, Müller A, Egle A, Erlacher M (2016) Bcl-2 proteins in development, health and disease of hematopoietic system. FEBS J 283(15):2779–2810CrossRefPubMedGoogle Scholar
  29. 29.
    Adams JM, Cory S (2007) The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26(9):1324–1337CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Weaver BA, Cleveland DW (2005) Decoding the links between mitotis, cancer and chemotherapy. The mitotic checkpoint, adaptation and cell death. Cancer Cell 8(1):7–12CrossRefPubMedGoogle Scholar
  31. 31.
    Sudo T, Nitta M, Saya H, Ueno NT (2004) Dependence of paclitaxel sensitivity on a functional spindle assembly checkpoint. Cancer Res 64(7):2502–2508CrossRefPubMedGoogle Scholar
  32. 32.
    Castilla C, Flores ML, Medina R, Pérez-Valderrama B, Romero F, Tortolero M, Japón MA, Sáez C (2014) Prostate cáncer cell response to paclitaxel is affected by abnormally expressed securin PTTG1. Mol Cancer Ther 13(10):2372–2383CrossRefPubMedGoogle Scholar
  33. 33.
    Flores ML, Castilla C, Gasca J, Medina R, Pérez-Valderrama B, Romero F, Japón MA, Sáez C (2016) Loss of PKCδ induces prostate cancer resistance to paclitaxel through activation of Wnt/β-catenin pathway and Mcl-1 accumulation. Mol Cancer Ther 15(7):1713–1725CrossRefPubMedGoogle Scholar
  34. 34.
    Flores ML, Castilla C, Ávila R, Ruiz-Borrego M, Sáez C, Japón MA (2012) Paclitaxel sensitivity of breast cáncer cells requires efficient mitotic arrest and disruption of Bcl-xL/Bak interaction. Breast Cancer Res Treat 133(3):917–928CrossRefPubMedGoogle Scholar
  35. 35.
    Gasca J, Flores ML, Giráldez S, Ruiz-Borrego M, Tortolero M, Romero F, Japón MA, Sáez C (2016) Loss of FBXW7 and accumulation of MCL1 and PLK1 promote paclitaxel resistance in breast cancer. Oncotarget 7:52751–52765CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Ho CH, Hsu JL, Liu SP, Hsu LC, Chang WL, Chao CC, Guh JH (2015) Repurposing of phentolamine as a potential anticancer agent against human castration-resistant prostate cancer: a central role on microtubule stabilization and mitochondrial apoptosis pathway. Prostate 75:1454–1466CrossRefPubMedGoogle Scholar
  37. 37.
    Hu Q, Sun W, Wang C, Gu Z (2016) Recent advances of cocktail chemotherapy by combination drug delivery systems. Adv Drug Deliv Rev 98:19–34CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, CSICUniversidad de SevillaSevilleSpain
  2. 2.Department of PathologyHospital Universitario Virgen del RocíoSevilleSpain

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