Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo activity against multiple myeloma.

Autor: Cholujova D; Cancer Research Institute, Biomedical Research Center SAS, Bratislava, Slovakia., Bujnakova Z; Institute of Geotechnics SAS, Košice, Slovakia., Dutkova E; Institute of Geotechnics SAS, Košice, Slovakia., Hideshima T; Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Groen RW; Department of Hematology, VU University Medical Center, Amsterdam, the Netherlands., Mitsiades CS; Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Richardson PG; Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Dorfman DM; Department of Medicine, Harvard Medical School, Boston, MA, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Balaz P; Institute of Geotechnics SAS, Košice, Slovakia., Anderson KC; Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Jakubikova J; Cancer Research Institute, Biomedical Research Center SAS, Bratislava, Slovakia.; Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana Farber Cancer Institute, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA.
Jazyk: angličtina
Zdroj: British journal of haematology [Br J Haematol] 2017 Dec; Vol. 179 (5), pp. 756-771. Date of Electronic Publication: 2017 Oct 19.
DOI: 10.1111/bjh.14974
Abstrakt: Multiple myeloma (MM), a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow, remains incurable despite the use of novel and conventional therapies. In this study, we demonstrated MM cell cytotoxicity triggered by realgar (REA; As 4 S 4 ) nanoparticles (NREA) versus Arsenic trioxide (ATO) against MM cell lines and patient cells. Both NREA and ATO showed in vivo anti-MM activity, resulting in significantly decreased tumour burden. The anti-MM activity of NREA and ATO is associated with apoptosis, evidenced by DNA fragmentation, depletion of mitochondrial membrane potential, cleavage of caspases and anti-apoptotic proteins. NREA induced G 2 /M cell cycle arrest and modulation of cyclin B1, p53 (TP53), p21 (CDKN1A), Puma (BBC3) and Wee-1 (WEE1). Moreover, NREA induced modulation of key regulatory molecules in MM pathogenesis including JNK activation, c-Myc (MYC), BRD4, and histones. Importantly, NREA, but not ATO, significantly depleted the proportion and clonogenicity of the MM stem-like side population, even in the context of the bone marrow stromal cells. Finally, our study showed that both NREA and ATO triggered synergistic anti-MM activity when combined with lenalidomide or melphalan. Taken together, the anti-MM activity of NREA was more potent compared to ATO, providing the preclinical framework for clinical trials to improve patient outcome in MM.
(© 2017 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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