A novel small molecule with potent anticancer activity inhibits cell growth by modulating intracellular labile zinc homeostasis.
Mol Cancer Ther
; 8(9): 2586-96, 2009 Sep.
Article
in En
| MEDLINE
| ID: mdl-19755513
ABSTRACT
ML-133 is a novel small molecule with potent antiproliferative activity, as shown in cancer cell lines and in a human colon tumor xenograft model. ML-133 reduces the concentration of intracellular labile zinc in HT-29 colon cancer cells, leading to induction of the Krüppel-like factor 4 transcription factor. Krüppel-like factor 4 displaces the positive regulator SP1 from the cyclin D1 promoter, thereby negatively regulating the expression of cyclin D1 and promoting the G(1)-S phase arrest of cell proliferation. The antiproliferative and antitumor activity of ML-133 described in the present study suggests modulation of intracellular zinc homeostasis as a potential strategy for the treatment of several cancer types, and ML-133 represents a promising new class of antitumor agents that deserves further development.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenanthrolines
/
Zinc
/
Cell Division
/
Homeostasis
/
Imidazoles
/
Antineoplastic Agents
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Mol Cancer Ther
Journal subject:
ANTINEOPLASICOS
Year:
2009
Type:
Article