Work

Conversion of Drug-Induced Differentiation to Apoptosis by Pharmacologic Cyclin-Dependent Kinase Inhibitors

Year: 2002

Type: article

Abstract: Recently, considerable attention has focused on the clinical development of novel anticancer agents which are intended to induce differentiation (i.e., protein kinase C activators and histone deacetylase inhibitors) or to inhibit cyclin-dependent kinases (CDKs) (i.e., flavopiridol and UCN-01). Because the differentiation process requires cell cycle arrest (e.g., in G(1)), the possibility arises that CDK inhibitors might potentiate the maturation response of neoplastic cells to various differentiation-inducing agents. However, recent findings indicate that contrary to expectations, pharmacologic CDK inhibitors fail to promote differentiation, at least in human leukemia cells; instead, they antagonize the maturation process and induce dysregulation of various cell cycle and apoptotic regulatory proteins that culminate in mitochondrial injury and apoptosis. A brief summary of the events that might contribute to these phenomena in human leukemia cells follows below. A better understanding of interactions between putative differentiation-inducers and cell cycle inhibitors may provide the foundation for the future development of novel chemotherapeutic strategies in hematopoietic and possibly non-hematopoietic malignancies.

Source: Cell Cycle

DOI: 10.4161/cc.1.6.260

Authors: Steven Grant, Paul Dent

Institutions: Virginia Commonwealth University, Virginia Commonwealth University Medical Center

Language: English

Topic: Cancer-related Molecular Pathways

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: Leukemia and Lymphoma Society, National Institutes of Health, National Cancer Institute