How does etoposide inhibit topoisomerase II?

Etoposide and other topo II inhibitors do not kill cells by blocking topoisomerase catalytic function. Rather they poison these enzymes by increasing the steady-state concentration of their covalent DNA cleavage complexes.

Does etoposide inhibit topoisomerase?

The functional activity of etoposide is to inhibit the topoisomerase II (topoII), which is an essential enzyme for DNA replication.

How does etoposide cause DNA damage?

Etoposide induces DNA breaks by inhibition of topoisomerase II (topoII) [17], an enzyme that induces transient DSBs as part of its enzymatic mechanism [18], [19], [20], [21]. TopoII is a homodimer, of which each monomer is able to cleave and religate one DNA strand [22].

What enzyme does etoposide inhibit?

Etoposide kills cells by stabilizing a covalent enzyme-cleaved DNA complex (known as the cleavage complex) that is a transient intermediate in the catalytic cycle of topoisomerase II.

Is etoposide a DNA intercalator?

Etoposide, a TopoII poison that does not intercalate into DNA, but rather covalently traps TopoII preferentially at induced DNA single-strand breaks [8], did not evict histones at therapeutic doses [7].

What is topoisomerase II in DNA replication?

Topoisomerase IIα is found at replication forks and remains tightly associated with chromosomes during mitosis [13,39]. Thus, topoisomerase IIα is believed to be the isoform that functions in growth-dependent processes, such as DNA replication and chromosome segregation [7,13].

How does staurosporine induce apoptosis?

Thus, staurosporine induces apoptotic cell death through at least two redundant parallel pathways. These two pathways normally coexist in L1210/S cells. However, the early cell death mechanism depending on caspase activation disguises the late caspase-independent apoptotic process.

How do you dilute etoposide?

Etoposide Injection must be diluted prior to use with Sodium chloride injection (0.9 % w/v) or glucose injection (5% w/v) to concentration of 0.2 mg/mL (i.e 1 ml of concentrate in 100 ml of diluent) to 0.4 mg/mL (i.e 2 ml of concentrate in 100 ml of diluent).