Alternative RNA Processing of Topoisomerase IIα in Etoposide-Resistant Human Leukemia K562 Cells: Intron Retention Results in a Novel C-Terminal Truncated 90-kDa Isoform.

DNA topoisomerase IIα (TOP2α) is a prominent target for anticancer drugs whose clinical efficacy is often limited by chemoresistance. Using antibody specific for the N-terminal of TOP2α, immunoassays indicated the existence of two TOP2α isoforms, 170 and 90 kDa, present in K562 leukemia cells and in an acquired etoposide (VP-16)-resistant clone (K/VP.5).

Hypophosphorylation of topoisomerase II in etoposide (VP-16)-resistant human leukemia K562 cells associated with reduced levels of beta II protein kinase C.

We selected and characterized a 30-fold etoposide (VP-16)-resistant subline of K562 human leukemia cells (K/VP.5) that exhibits quantitative and qualitative changes in topoisomerase II, including hypophosphorylation of this drug target. The initial rate of topoisomerase II phosphorylation was reduced 3-fold in K/VP.

Induction of apoptosis in murine and human neuroblastoma cell lines by the enediyne natural product neocarzinostatin.

Neocarzinostatin (NCS) is a naturally occurring enediyne antitumor agent that produces single- and double-strand breaks in cellular DNA. We have previously shown that treatment of human (SK-N-SH) and murine (NB41A3) neuroblastoma cells with NCS results in cell death for a subpopulation within the culture. The remaining cells undergo mitotic arrest with morphological differentiation along glial lines.

Differential induction of etoposide-mediated apoptosis in human leukemia HL-60 and K562 cells.

Etoposide (VP-16) is one of several DNA-damaging agents that induce subcellular structural changes associated with apoptosis. VP-16 exerts its DNA-damaging and cytotoxic effects subsequent to interference with DNA topoisomerase II activity. VP-16 also stimulates c-jun and c-fos mRNA expression in some cell lines, including human leukemia K562 and HL-60 cells.

Increased c-jun/AP-1 levels in etoposide-resistant human leukemia K562 cells.

C-jun mRNA and AP-1 levels were examined in etoposide (VP-16)-sensitive (K562) and -resistant (K/VP.5) human leukemia cell lines. Previously, we reported that K/VP.