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PTHrP attenuates osteoblast cell death and apoptosis induced by a novel class of anti-cancer agents

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Abstract

The effectiveness of chemotherapeutic agents often limits their use due to their negative effects on normal cells. Apoptosis regulatory protein (CARP)-1 functional mimetics (CFMs) belong to a novel class of compounds that possess anti-cancer properties with potential utility in breast and other cancers. In this study, we investigated the growth inhibitory action of CFM-4 and -5 in bone-forming osteoblasts and role of a skeletal regulator, parathyroid hormone (PTH)-related peptide (PTHrP), which is frequently associated with oncologic pathologies. MC3T3E1-clone4 (MC-4) or primary osteoblasts were treated with CFMs. Western blots were performed to determine specific protein expressions. MTT, TUNEL assay, ethidium bromide/acridine orange staining, and ApoAlert caspase profiling were used to investigate cell viability and apoptosis of osteoblasts. Immunofluorescence staining was performed to observe intracellular localization of CARP-1. Our studies revealed that CFM-4 and -5 suppressed growths of mature differentiated, but not proliferating, MC-4 cells and PTHrP attenuated this effect. Mechanistically, induction of CARP-1 protein by CFM-4 and -5 was partially decreased by PTHrP. While CARP-1 increased by CFM-4 or -5 correlated with activated caspase-3, PTHrP remarkably blocked caspase-3 activation. PTHrP also influenced translocation of CFM-induced CARP-1 from the nucleus to the cytoplasm. Our data identify a new function of PTHrP in maintaining osteoblast homeostasis in chemotherapy and define a role of CARP-1 in this process. The crosstalk of PTHrP and CFM-4 and -5 signaling highlights the importance of CFMs as potential anti-cancer therapeutics in breast and other cancers which adversely affect bone.

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References

  1. R.C. Gensure, T.J. Gardella, H. Juppner, Parathyroid hormone and parathyroid hormone-related peptide, and their receptors. Biochem. Biophys. Res. Commun. 328, 666–678 (2005)

    Article  CAS  PubMed  Google Scholar 

  2. D. Miao, B. He, Y. Jiang, T. Kobayashi, M.A. Soroceanu, J. Zhao, H. Su, X. Tong, N. Amizuka, A. Gupta, H.K. Genant, H.M. Kronenberg, D. Goltzman, A.C. Karaplis, Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH 1-34. J. Clin. Invest. 115, 2402–2411 (2005)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. D. Miao, H. Su, B. He, J. Gao, Q. Xia, M. Zhu, Z. Gu, D. Goltzman, A.C. Karaplis, Severe growth retardation and early lethality in mice lacking the nuclear localization sequence and C-terminus of PTH-related protein. Proc. Natl. Acad. Sci. USA 105, 20309–20314 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. W.M. Philbrick, B.E. Dreyer, I.A. Nakchbandi, A.C. Karaplis, Parathyroid hormone-related protein is required for tooth eruption. Proc. Natl. Acad. Sci. USA 95, 11846–11851 (1998)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. L.K. McCauley, T.J. Martin, Twenty-five years of PTHrP progress: from cancer hormone to multifunctional cytokine. J. Bone Miner. Res. 27, 1231–1239 (2012)

    Article  CAS  PubMed  Google Scholar 

  6. T.J. Martin, J.M. Moseley, M.T. Gillespie, Parathyroid hormone-related protein: biochemistry and molecular biology. Crit. Rev. Biochem. Mol. Biol. 26, 377–395 (1991)

    Article  CAS  PubMed  Google Scholar 

  7. L.F. de Castro, D. Lozano, S. Portal-Nunez, M. Maycas, M. De la Fuente, J.R. Caeiro, P. Esbrit, Comparison of the skeletal effects induced by daily administration of PTHrP (1-36) and PTHrP (107–139) to ovariectomized mice. J. Cell. Physiol. 227, 1752–1760 (2012)

    Article  PubMed  Google Scholar 

  8. E. Bucht, H. Rong, Y. Pernow, A.C. Nordqvist, E. Eriksson, W. Rankin, E. von Schoultz, W.J. Burtis, B. Granberg, U.G. Falkmer, D.W. Burton, L.J. Deftos, Parathyroid hormone-related protein in patients with primary breast cancer and eucalcemia. Cancer Res. 58, 4113–4116 (1998)

    CAS  PubMed  Google Scholar 

  9. N. Kohno, S. Kitazawa, M. Fukase, Y. Sakoda, Y. Kanbara, Y. Furuya, O. Ohashi, Y. Ishikawa, Y. Saitoh, The expression of parathyroid hormone-related protein in human breast cancer with skeletal metastases. Surg. Tod. 24, 215–220 (1994)

    Article  CAS  Google Scholar 

  10. Y. Nishigaki, Y. Ohsaki, E. Toyoshima, K. Kikuchi, Increased serum and urinary levels of a parathyroid hormone-related protein COOH terminus in non-small cell lung cancer patients. Clin. Cancer Res. 5, 1473–1481 (1999)

    CAS  PubMed  Google Scholar 

  11. K.M. Dougherty, E.A. Blomme, A.J. Koh, J.E. Henderson, K.J. Pienta, T.J. Rosol, L.K. McCauley, Parathyroid hormone-related protein as a growth regulator of prostate carcinoma. Cancer Res. 59, 6015–6022 (1999)

    CAS  PubMed  Google Scholar 

  12. L.J. Deftos, I. Barken, D.W. Burton, R.M. Hoffman, J. Geller, Direct evidence that PTHrP expression promotes prostate cancer progression in bone. Biochem. Biophys. Res. Commun. 327, 468–472 (2005)

    Article  CAS  PubMed  Google Scholar 

  13. G.R. Mundy, Metastasis to bone: causes, consequences and therapeutic opportunities. Nature reviews. Cancer 2, 584–593 (2002)

    CAS  PubMed  Google Scholar 

  14. K.N. Weilbaecher, T.A. Guise, L.K. McCauley, Cancer to bone: a fatal attraction. Nat. Rev. Cancer 11, 411–425 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. G. Brunetti, G. Colaianni, M.F. Faienza, S. Colucci, G. Grano, Osteotropic cancers: from primary tumor to bone. Clin. Rev. Bone Miner. Metab. 11, 94–102 (2013)

    Article  CAS  Google Scholar 

  16. G.R. Mundy, J.R. Edwards, PTH-related peptide (PTHrP) in hypercalcemia. J. Am. Soc. Nephrol. 19, 672–675 (2008)

    Article  CAS  PubMed  Google Scholar 

  17. R. Kremer, J. Li, A. Camirand, A.C. Karaplis, Parathyroid hormone related protein (PTHrP) in tumor progression. Adv. Exp. Med. Biol. 720, 145–160 (2011)

    Article  CAS  PubMed  Google Scholar 

  18. J. Li, A.C. Karaplis, D.C. Huang, P.M. Siegel, A. Camirand, X.F. Yang, W.J. Muller, R. Kremer, PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target. J. Clin. Invest. 121, 4655–4669 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. M. Akhtari, J. Mansuri, K.A. Newman, T.M. Guise, P. Seth, Biology of breast cancer bone metastasis. Cancer Biol. Ther. 7, 3–9 (2008)

    Article  CAS  PubMed  Google Scholar 

  20. M.A. Henderson, J.A. Danks, J.L. Slavin, G.B. Byrnes, P.F. Choong, J.B. Spillane, T.J. Martin, J.L. Hopper, Parathyroid hormone-related protein localization in breast cancers predict improved prognosis. Cancer Res. 66, 2250–2256 (2006)

    Article  CAS  PubMed  Google Scholar 

  21. N.S. Datta, A.B. Abou-Samra, PTH and PTHrP signaling in osteoblasts. Cell Signal. 21, 1245–1254 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. E. Maioli, V. Fortino, The complexity of parathyroid hormone-related protein signalling. Cell Mol. Life Sci. 61, 257–262 (2004)

    Article  CAS  PubMed  Google Scholar 

  23. Q. Zhu, X. Zhou, M. Zhu, Q. Wang, D. Goltzman, A. Karaplis, D. Miao, Endogenous parathyroid hormone-related protein compensates for the absence of parathyroid hormone in promoting bone accrual in vivo in a model of bone marrow ablation. J. Bone Miner. Res. 28, 1898–1911 (2013)

    Article  CAS  PubMed  Google Scholar 

  24. R.L. Jilka, R.S. Weinstein, A.M. Parfitt, S.C. Manolaga, Quantifying osteoblast and osteocyte apoptosis: challenges and rewards. J. Bone Miner. Res. 22, 1492–1501 (2007)

    Article  PubMed  Google Scholar 

  25. A.K. Rishi, L. Zhang, M. Boyanapalli, A. Wali, R.M. Mohammad, Y. Yu, J.A. Fontana, J.S. Hatfield, M.I. Dawson, A.P. Majumdar, U. Reichert, Identification and characterization of a cell cycle and apoptosis regulatory protein-1 as a novel mediator of apoptosis signaling by retinoid CD437. J. Biol. Chem. 278, 33422–33435 (2003)

    Article  CAS  PubMed  Google Scholar 

  26. J.H. Kim, C.K. Yang, K. Heo, R.G. Roeder, W. An, M.R. Stallcup, CCAR1, a key regulator of mediator complex recruitment to nuclear receptor transcription complexes. Mol. Cell 31, 510–519 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. A.K. Rishi, L. Zhang, Y. Yu, Y. Jiang, J. Nautiyal, A. Wali, J.A. Fontana, E. Levi, A.P. Majumdar, Cell cycle- and apoptosis-regulatory protein-1 is involved in apoptosis signaling by epidermal growth factor receptor. J. Biol. Chem. 281, 13188–13198 (2006)

    Article  CAS  PubMed  Google Scholar 

  28. V.T. Puliyappadamba, W. Wu, D. Bevis, L. Zhang, L. Polin, R. Kilkuskie, R.L. Finley Jr, S.D. Larsen, E. Levi, F.R. Miller, A. Wali, A.K. Rishi, Antagonists of anaphase-promoting complex (APC)-2-cell cycle and apoptosis regulatory protein (CARP)-1 interaction are novel regulators of cell growth and apoptosis. J. Biol. Chem. 286, 38000–38017 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. L. Zhang, E. Levi, P. Majumder, Y. Yu, A. Aboukameel, J. Du, H. Xu, R. Mohammad, J.S. Hatfield, A. Wali, V. Adsay, A.P. Majumdar, A.K. Rishi, Transactivator of transcription-tagged cell cycle and apoptosis regulatory protein-1 peptides suppress the growth of human breast cancer cells in vitro and in vivo. Mol. Cancer Ther. 6, 1661–1672 (2007)

    Article  CAS  PubMed  Google Scholar 

  30. A.E. Ashour, S. Jamal, V.T. Cheryan, M. Muthu, K.M. Zoheir, A.M. Alafeefy, A.R. Abd-Allah, E. Levi, A.L. Tarca, L.A. Polin, A.K. Rishi, CARP-1 functional mimetics: a novel class of small molecule inhibitors of medulloblastoma cell growth. PLoS One 8, e66733 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. S. Jamal, V.T. Cheriyan, M. Muthu, S. Munie, E. Levi, A.E. Ashour, H.I. Pass, A. Wali, M. Singh, A.K. Rishi, CARP-1 functional mimetics are a novel class of small molecule inhibitors of malignant pleural mesothelioma cells. PLoS One 9, e89146 (2014)

    Article  PubMed Central  PubMed  Google Scholar 

  32. M. Muthu, J. Somagoni, V.T. Cheriyan, S. Munie, E. Levi, A.E. Ashour, A.E.B. Yassin, A.M. Alafeefy, P. Sochacki, L. Polin, K.B. Reddy, S.D. Larsen, M. Singh, A.K. Rishi, Identification and testing of novel CARP-1 functional mimetic compounds as inhibitors of non-small cell lung and triple negative breast cancers. J. Biomed. Nanotechnol. 11, 1–20 (2015)

    Article  Google Scholar 

  33. J.H. Davies, B.A. Evans, M.E. Jenney, J.W. Gregory, Effects of chemotherapeutic agents on the function of primary human osteoblast-like cells derived from children. J. Clin. Endocrinol. Metab. 88, 6088–6097 (2003)

    Article  CAS  PubMed  Google Scholar 

  34. S.L. Rellick, H. O’Leary, D. Piktel, C. Walton, J.E. Fortney, S.M. Akers, K.H. Martin, J. Denvir, G. Boskovic, D.A. Primerano, J. Vos, N. Bailey, M. Gencheva, L.F. Gibson, Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One 7, e30758 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. S. Aggarwal, J. Kamboj, R. Arora, Chemotherapy-related cardiotoxicity. Ther. Adv. Cardiovasc. Dis. 7, 87–98 (2013)

    Article  PubMed  Google Scholar 

  36. S. Sharma, C. Mahalingam, V. Das, S. Jamal, E. Levi, A.K. Rishi, N.S. Datta, Cell cycle and apoptosis regulatory protein (CARP)-1 is expressed in osteoblasts and regulated by PTH. Biochem. Biophys. Res. Commun. 436, 607–612 (2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. D. Wang, K. Christensen, K. Chawla, G. Xiao, P.H. Krebsbach, R.T. Franceschi, Isolation and characterization of MC3T3-E1 preosteoblast subclones with distinct in vitro and in vivo differentiation/mineralization potential. J. Bone Miner. Res. 14, 893–903 (1999)

    Article  CAS  PubMed  Google Scholar 

  38. N.S. Datta, C. Chen, J.E. Berry, L.K. McCauley, PTHrP signaling targets cyclin D1 and induces osteoblastic cell growth arrest. J. Bone Miner. Res. 20, 1051–1064 (2005)

    Article  CAS  PubMed  Google Scholar 

  39. N.S. Datta, G.J. Pettway, C. Chen, A.J. Koh, L.K. McCauley, Cyclin D1 as a target for the proliferative effects of PTH and PTHrP in early osteoblastic cells. J. Bone Miner. Res. 22, 951–964 (2007)

    Article  CAS  PubMed  Google Scholar 

  40. C.D. Mahalingam, T. Datta, R.V. Patil, J. Kreider, R.D. Bonfil, K.L. Kirkwood, S.A. Goldstein, A.B. Abou-Samra, N.S. Datta, Mitogen activated protein kinase phosphatase-1 regulates bone mass, osteoblast gene expression, and responsiveness to parathyroid hormone. J. Endocrinol. 211, 145–156 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. D. Ribble, N.B. Goldstein, D.A. Norris, Y.G. Shellman, A simple technique for quantifying apoptosis in 96-well plates. BMC Biotechnol. 5, 12 (2005)

    Article  PubMed Central  PubMed  Google Scholar 

  42. S. Kasibhatla, G.P. Amarante-Mendes, D. Finucane, T. Brunner, E. Bossy-Wetzel, D.R. Green, Acridine orange/ethidium bromide (AO/EB) staining to detect apoptosis. CSH Protoc. (2006). doi:10.1101/pdb.prot4493

    Google Scholar 

  43. M. Hervy, L.M. Hoffman, C.C. Jensen, M. Smith, M.C. Beckerle, The LIM protein zyxin binds CARP-1 and promotes apoptosis. Genes Cancer 1, 506–515 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  44. A.H. Stegh, O. Schickling, A. Ehret, C. Scaffidi, C. Peterhansel, T.G. Hofmann, I. Grummt, P.H. Krammer, M.E. Peter, DEDD, a novel death effector domain-containing protein, targeted to the nucleolus. EMBO J. 17, 5974–5986 (1998)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  45. M.G. Valmiki, J.W. Ramos, Death effector domain-containing proteins. Cell. Mol. Life Sci. 66, 814–830 (2009)

    Article  CAS  PubMed  Google Scholar 

  46. D.R. Clohisy, S.L. Perkins, M.L. Ramnaraine, Review of cellular mechanisms of tumor osteolysis. Clin. Orthop. Relat. Res. 373, 104–114 (2000)

    Article  PubMed  Google Scholar 

  47. M. Kinder, E. Chislock, K.M. Bussard, L. Shuman, A.M. Mastro, Metastatic breast cancer induces an osteoblast inflammatory response. Exp. Cell Res. 314, 173–183 (2008)

    Article  CAS  PubMed  Google Scholar 

  48. P.A. Phadke, R.R. Mercer, J.F. Harms, Y. Jia, A.R. Frost, J.L. Jewell, K.M. Bussard, S. Nelson, C. Moore, J.C. Kappes, C.V. Gay, A.M. Mastro, D.R. Welch, Kinetics of metastatic breast cancer cell trafficking in bone. Clin. Cancer Res. 12, 1431–1440 (2006)

    Article  PubMed Central  PubMed  Google Scholar 

  49. D. Miao, J. Li, Y. Xue, H. Su, A.C. Karaplis, D. Goltzman, Parathyroid hormone-related peptide is required for increased trabecular bone volume in parathyroid hormone-null mice. Endocrinology 145, 3554–3562 (2004)

    Article  CAS  PubMed  Google Scholar 

  50. M. Nishihara, M. Ito, T. Tomioka, A. Ohtsuru, T. Taguchi, T. Kanematsu, Clinicopathological implications of parathyroid hormone-related protein in human colorectal tumours. J. Pathol. 187, 217–222 (1999)

    Article  CAS  PubMed  Google Scholar 

  51. M.W. Kissin, M.A. Henderson, J.A. Danks, J.A. Hayman, R.C. Bennett, T.J. Martin, Parathyroid hormone related protein in breast cancers of widely varying prognosis. Eur. J. Surg. Oncol. 19, 134–142 (1993)

    CAS  PubMed  Google Scholar 

  52. P.R. Montgrain, L.J. Deftos, D. Arenberg, A. Tipps, R. Quintana, S. Carskadon, R.H. Hastings, Prognostic implications of parathyroid hormone-related protein in males and females with non-small-cell lung cancer. Clin. Lung Cancer. 12, 197–205 (2011)

    Article  PubMed  Google Scholar 

  53. M. Bendre, D. Gaddy, R.W. Nicholas, L.J. Suva, Breast cancer metastasis to bone: it is not all about PTHrP. Clin. Orthop. Relat. Res. 415(suppl), S39–S45 (2003)

    Article  PubMed  Google Scholar 

  54. Y. Zheng, H. Zhou, K. Brennan, J.M. Blair, J.R. Modzelewski, M.J. Seibel, C.R. Dunstan, Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis. Bone 40, 471–478 (2007)

    Article  CAS  PubMed  Google Scholar 

  55. Y. Zheng, S.O. Chow, K. Boernert, D. Basel, A. Mikuscheva, S. Kim, C. Fong-Yee, T. Trivedi, F. Buttgereit, R.L. Sutherland, C.R. Dunstan, H. Zhou, M.J. Seibel, Direct crosstalk between cancer and osteoblast lineage cells fuels metastatic growth in bone via auto-amplification of IL-6 and RANKL signaling pathways. J. Bone Miner. Res. 29, 1938–1949 (2014)

    Article  CAS  PubMed  Google Scholar 

  56. H. Takasu, T.J. Gardella, M.D. Luck, J.T. Potts Jr, F.R. Bringhurst, Amino-terminal modifications of human parathyroid hormone (PTH) selectively alter phospholipase C signaling via the type 1 PTH receptor: implications for design of signal-specific PTH ligands. Biochemistry 38, 13453–13460 (1999)

    Article  CAS  PubMed  Google Scholar 

  57. N.S. Datta, R. Kolailat, A. Fite, G. Pettway, A.B. Abou-Samra, Distinct roles for mitogen-activated protein kinase phosphatase-1 (MKP-1) and ERK-MAPK in PTH1R signaling during osteoblast proliferation and differentiation. Cell Signal. 22, 457–466 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. J.M. Lee, G.I. Im, PTHrP isoforms have differing effect on chondrogenic differentiation and hypertrophy of mesenchymal stem cells. Biochem. Biophys. Res. Commun. 421, 819–824 (2012)

    Article  CAS  PubMed  Google Scholar 

  59. A.G. Porter, R.U. Janicke, Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6, 99–104 (1999)

    Article  CAS  PubMed  Google Scholar 

  60. W. Roth, F. Stenner-Liewen, K. Pawlowski, A. Godzik, J.C. Reed, Identification and characterization of DEDD2, a death effector domain-containing protein. J. Biol. Chem. 277, 7501–7508 (2002)

    Article  CAS  PubMed  Google Scholar 

  61. A. Alcivar, S. Hu, J. Tang, X. Yang, DEDD and DEDD2 associate with caspase-8/10 and signal cell death. Oncogene 22, 291–297 (2003)

    Article  CAS  PubMed  Google Scholar 

  62. J.C. Lee, O. Schickling, A.H. Stegh, R.G. Oshima, D. Dinsdale, G.M. Cohen, M.E. Peter, DEDD regulates degradation of intermediate filaments during apoptosis. J. Cell Biol. 158, 1051–1066 (2002)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  63. O. Schickling, A.H. Stegh, J. Byrd, M.E. Peter, Nuclear localization of DEDD leads to caspase-6 activation through its death effector domain and inhibition of RNA polymerase I dependent transcription. Cell Death Differ. 8, 1157–1168 (2001)

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Institutional Funding for Medical Research and Education (FMRE) to N. S. D; and the Medical Research Services of the Department of Veteran Affairs Merit Review Grant to A. K. R. The authors acknowledge Sara Munie for technical assistance.

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Authors and Affiliations

  1. Division of Endocrinology, Department of Internal Medicine, Wayne State University School of Medicine, 1107 Elliman Clinical Research Building, 421 East Canfield Avenue, Detroit, MI, 48201, USA

    Sahiti Chukkapalli & Nabanita S. Datta

  2. Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Arun K. Rishi & Nabanita S. Datta

  3. Department of Pathology, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Edi Levi

  4. VA Medical Center, Detroit, MI, 48201, USA

    Edi Levi & Arun K. Rishi

  5. Department of Oncology, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Arun K. Rishi

  6. Cardiovascular Research Institute, Wayne State University School of Medicine, Detroit, MI, 48201, USA

    Nabanita S. Datta

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  1. Sahiti Chukkapalli
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Chukkapalli, S., Levi, E., Rishi, A.K. et al. PTHrP attenuates osteoblast cell death and apoptosis induced by a novel class of anti-cancer agents. Endocrine 51, 534–544 (2016). https://doi.org/10.1007/s12020-015-0699-2

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