The HSP70 Modulator MAL3-101 Inhibits Merkel Cell Carcinoma
作者： Christian Adam , Anne Baeurle , Jeffrey L Brodsky , Peter Wipf , David Schrama
DOI: 10.1371/JOURNAL.PONE.0092041
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摘要: Merkel Cell Carcinoma (MCC) is a rare and highly aggressive neuroendocrine skin cancer for which no effective treatment available. MCC represents human with the best experimental evidence causal role of polyoma virus. Large T antigens (LTA) encoded by viruses are oncoproteins, thought to require support cellular heat shock protein 70 (HSP70) exert their transforming activity. Here we evaluated capability MAL3-101, synthetic HSP70 inhibitor, limit proliferation survival various cell lines. Remarkably, MAL3-101 resulted in considerable apoptosis 5 out 7 While this effect was not associated viral status cells, quantitative mRNA expression analysis known isoforms revealed significant correlation between sensitivity HSC70 expression, most prominent isoform all Moreover, also exhibited vivo antitumor activity an xenograft model suggesting that substance or related compounds potential therapeutics future.
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R. E. Wang, Targeting heat shock proteins 70/90 and proteasome for cancer therapy. Current Medicinal Chemistry. ,vol. 18, pp. 4250- 4264 ,(2011) , 10.2174/092986711797189574
David A. Gewirtz, Yong-Mei Di, Joyce K. Randolph, Pramod T. Jain, Kristoffer Valerie, Sharon Bullock, Niharika Nath, Srikumar P. Chellappan, Rb dephosphorylation and suppression of E2F activity in human breast tumor cells exposed to a pharmacological concentration of estradiol. Archives of Biochemistry and Biophysics. ,vol. 388, pp. 243- 252 ,(2001) , 10.1006/ABBI.2000.2278
Christoph Willmes, Christian Adam, Miriam Alb, Lena Völkert, Roland Houben, Jürgen C. Becker, David Schrama, Type I and II IFNs Inhibit Merkel Cell Carcinoma via Modulation of the Merkel Cell Polyomavirus T Antigens Cancer Research. ,vol. 72, pp. 2120- 2128 ,(2012) , 10.1158/0008-5472.CAN-11-2651
Natalie J. Miller, Shailender Bhatia, Upendra Parvathaneni, Jayasri G. Iyer, Paul Nghiem, Emerging and Mechanism-Based Therapies for Recurrent or Metastatic Merkel Cell Carcinoma Current Treatment Options in Oncology. ,vol. 14, pp. 249- 263 ,(2013) , 10.1007/S11864-013-0225-9
JESPER NYLANDSTED, KARSTEN BRAND, MARJA JÄÄTTELÄ, Heat Shock Protein 70 Is Required for the Survival of Cancer Cells Annals of the New York Academy of Sciences. ,vol. 926, pp. 122- 125 ,(2006) , 10.1111/J.1749-6632.2000.TB05605.X
Maria Agelli, Limin X. Clegg, Jürgen C. Becker, Dana E. Rollison, The etiology and epidemiology of merkel cell carcinoma. Current Problems in Cancer. ,vol. 34, pp. 14- 37 ,(2010) , 10.1016/J.CURRPROBLCANCER.2010.01.001
Carlo Pincelli, Anne R. Haake, Luisa Benassi, Emanuela Grassilli, Cristina Magnoni, Daniela Ottani, Renata Polakowska, Claudio Franceschi, Alberto Giannetti, Autocrine nerve growth factor protects human keratinocytes from apoptosis through its high affinity receptor (TRK): A role for BCL-2 Journal of Investigative Dermatology. ,vol. 109, pp. 757- 764 ,(1997) , 10.1111/1523-1747.EP12340768
Mikkel Rohde, Mads Daugaard, Mette Hartvig Jensen, Kristian Helin, Jesper Nylandsted, Marja Jäättelä, Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms Genes & Development. ,vol. 19, pp. 570- 582 ,(2005) , 10.1101/GAD.305405
M Fakiha, P Letertre, JP Vuillez, J Lebeau, Remission of Merkel cell tumor after somatostatin analog treatment Journal of Cancer Research and Therapeutics. ,vol. 6, pp. 382- 384 ,(2010) , 10.4103/0973-1482.73352
U. Moens, M. Van Ghelue, M. Johannessen, Oncogenic potentials of the human polyomavirus regulatory proteins. Cellular and Molecular Life Sciences. ,vol. 64, pp. 1656- 1678 ,(2007) , 10.1007/S00018-007-7020-3