Antitumor activity of CDA-â
¡, a urinary preparation, on human multiple myeloma cell lines via the mitochondrial pathway.
Mol Med Rep
; 9(3): 1025-31, 2014 Mar.
Article
in En
| MEDLINE
| ID: mdl-24452179
Cell differentiation agent II (CDAII) is a DNA methyltransferase inhibitor isolated from healthy human urine. In the present study, the antitumor activity of CDAII on human multiple myeloma (MM) cell lines via the mitochondrial pathway was first revealed. The human MM cell lines were exposed to CDAII. Cytotoxicity, caspase activation, apoptosis and the effects on the mitochondrial pathway were assessed. CDAâ
¡ was capable of decreasing the depolarized mitochondrial membranes and activating caspase3 and 9 and poly (ADPribose) polymerase in MM cells treated with CDAII. CDAII induced caspasedependent cell death accompanied by a significant decrease in X-linked inhibitor of apoptosis protein (XIAP), survivin and Mcl1 levels. The caspase3 inhibitor, ZDEVDFMK, inhibited CDAIIinduced apoptosis. CDAII potently increased the Bax levels, decreased the Bcl2/Bax ratio and decreased the expression of the downstream targets of NFκB. In conclusion, the results of the present study demonstrated that CDAII treatment leads to the inhibition of p65 nuclear localization and potently induces caspasedependent apoptosis in MM cells mediated through the mitochondrial pathway at low nanomolar concentrations. These results indicate that CDAII is a novel inhibitor of NFκB activity, with notable antimyeloma efficacy. This study provides a rationale for the clinical investigation of CDAâ
¡ in human MM.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Phenylacetates
/
Apoptosis
/
Mitochondria
/
Multiple Myeloma
/
Antineoplastic Agents
Limits:
Humans
Language:
En
Journal:
Mol Med Rep
Year:
2014
Document type:
Article
Country of publication: