Ironing out the role of the cyclin-dependent kinase inhibitor, p21 in cancer: Novel iron chelating agents to target p21 expression and activity.
Free Radic Biol Med
; 133: 276-294, 2019 03.
Article
en En
| MEDLINE
| ID: mdl-29572098
ABSTRACT
Iron (Fe) has become an important target for the development of anti-cancer therapeutics with a number of Fe chelators entering human clinical trials for advanced and resistant cancer. An important aspect of the activity of these compounds is their multiple molecular targets, including those that play roles in arresting the cell cycle, such as the cyclin-dependent kinase inhibitor, p21. At present, the exact mechanism by which Fe chelators regulate p21 expression remains unclear. However, recent studies indicate the ability of chelators to up-regulate p21 at the mRNA level was dependent on the chelator and cell-type investigated. Analysis of the p21 promoter identified that the Sp1-3-binding site played a significant role in the activation of p21 transcription by Fe chelators. Furthermore, there was increased Sp1/ER-α and Sp1/c-Jun complex formation in melanoma cells, suggesting these complexes were involved in p21 promoter activation. Elucidating the mechanisms involved in the regulation of p21 expression in response to Fe chelator treatment in neoplastic cells will further clarify how these agents achieve their anti-tumor activity. It will also enhance our understanding of the complex roles p21 may play in neoplastic cells and lead to the development of more effective and specific anti-cancer therapies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Quelantes del Hierro
/
Inhibidor p21 de las Quinasas Dependientes de la Ciclina
/
Hierro
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Free Radic Biol Med
Asunto de la revista:
BIOQUIMICA
/
MEDICINA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Australia