What happens when you inhibit topoisomerase?
Topoisomerase inhibitors block the ligation step of the cell cycle, which generates DNA single- and double-strand breaks, leading to apoptotic cell death.
What happens if topoisomerase II is inhibited?
Inhibitors of topoisomerases I and II freeze these enzymes as protein-DNA complexes at various steps in their reaction pathways (31, 49). Topoisomerase-DNA-inhibitor complexes (cleavable complexes) are poisoned and are unable to execute a complete enzymatic cycle.
How do topoisomerase inhibitors affect cancer cells?
Topoisomerase inhibitors (TI) can inhibit cell proliferation by preventing DNA replication, stimulating DNA damage and inducing cell cycle arrest. Although these agents have been commonly used in the chemotherapy for the anti-proliferative effect, their impacts on the metastasis of cancer cells remain obscure.
What is a topoisomerase 1 inhibitor?
Topoisomerase I inhibitors are a new class of anticancer agents with a mechanism of action aimed at interrupting DNA replication in cancer cells, the result of which is cell death. Most if not all Topoisomerase I inhibitors are derivatives of the plant extract camptothecin.
What is the job of topoisomerase?
Topoisomerase: A class of enzymes that alter the supercoiling of double-stranded DNA. (In supercoiling the DNA molecule coils up like a telephone cord, which shortens the molecule.) The topoisomerases act by transiently cutting one or both strands of the DNA.
Which of the following drugs inhibits bacterial topoisomerase?
Fluoroquinolones. Fluoroquinolones inhibit bacterial cell proliferation by inhibiting DNA gyrase and topoisomerase IV, both essential enzymes in bacterial DNA transcription and replication (Hooper, 2001).
What are topoisomerase II inhibitors?
A substance that blocks the activity of the enzyme topoisomerase II, which cuts and repairs tangled strands of DNA. Topoisomerase II is involved in cell division and growth, so blocking activity of this enzyme may kill cancer cells. Some topoisomerase II inhibitors are being used to treat cancer.
How do topoisomerase II inhibitors work?
Inhibitors of the mammalian enzymes are widely used antitumor drugs. They stabilize topoisomerase-DNA cleavable complexes by hindering the DNA relegating step of the catalytic reaction, thus resulting in DNA cleavage stimulation. Topoisomerase II inhibitors may also have genotoxic effects.
Why would a topoisomerase inhibitor be a potential inhibitor of rapidly dividing cancer cells?
Mechanism. TopII forms a homodimer that functions by cleaving double stranded DNA, winding a second DNA duplex through the gap, and re-ligating the strands. TopII is necessary for cell proliferation and is abundant in cancer cells, which make TopoII inhibitors effective anti-cancer treatments.
What problems can be caused by mitotic inhibitors?
Mitotic inhibitors interfere with the assembly and disassembly of tubulin into microtubule polymers. This interrupts cell division, usually during the mitosis (M) phase of the cell cycle when two sets of fully formed chromosomes are supposed to separate into daughter cells.
What is the difference between topoisomerase 1 and 2?
Topoisomerase I and II are methods of dealing with supercoiled DNA. Topoisomerase I cuts one strand in the double-stranded DNA and no ATP is required for its function. On the other hand Topoisomerase, II cuts both strands in DNA and needs ATP for its activity. This is the key difference between Topoisomerase I and II.
Are there any drugs that block Topoisomerase 2?
Topoisomerase inhibitors in current use in the United States include irinotecan and topotecan, inhibitors of topoisomerase I, and etoposide and teniposide, inhibitors of topoisomerase II. All four agents are semisynthetic analogues of natural toxins that were initially identified in plants.
Can a topoisomerase inhibitor cause sudden death?
On rare occasions it has lead to sudden death as a result of arrhythmia or hypotension. Although topoisomerase inhibitors are used as anticancer treatments, topoisomerase inhibition has been linked to promoting some cancers, particularly leukemia. The reason is that some of the cells with fragmented DNA survive.
What’s the difference between topoisomerase 1 and 2?
Their mechanism is analogous to that of the fluoroquinolone class of antibiotics. The camptothecins are topoisomerase I inhibitors, whereas the podophyllotoxins are topoisomerase II inhibitors.
What are the side effects of topo II inhibitors?
For one hand, the traditional topo I inhibitors (e.g., CPT) have significant dose-limiting toxicities and drug resistance; for another hand, the treatment with topo II targeting drugs may result in secondary malignancies, which may due to the inhibition of topo IIβ [ [9], [10], [11] ].