Is camptothecin an antibiotic?
This review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor antibiotic. Two camptothecin analogues are presently approved for use in the clinic as antitumor agents and several others are in clinical trials.
What is camptothecin used to treat?
Camptothecin, an quinolone alkaloid, is used as a chemotherapeutic agent in the treatment of leukemia (Jones et al., 1997). Camptothecin complexes with type I DNA topoisomerase inhibiting both cleavage and religation reactions of DNA replication thus arresting growth of L.
What does camptothecin do to DNA?
Camptothecin selectively poisons topoisomerase I by trapping topoisomerase I cleavage complexes, which correspond to enzyme-linked DNA breaks (for a review see Pommier, 1996). Camptothecin induces replication-dependent DNA lesions, and arrests cells in the S and G2 phase of the cell cycle.
Does camptothecin target DNA replication?
Camptothecin is a potent anticancer agent producing well-characterized replication-mediated DNA double-strand breaks through the collision of replication forks with topoisomerase I cleavage complexes.
How does camptothecin cause apoptosis?
Camptothecin caused apoptosis in SiHa cells by inducing mitochondrial membrane permeability changes that lead to the loss of mitochondrial membrane potential, decreased Bcl-2 levels, cytochrome c release, caspase-3 activation, formation of reactive oxygen species and depletion of GSH.
How does camptothecin cause DNA damage?
Camptothecin selectively poisons topoisomerase I by trapping topoisomerase I cleavage complexes, which correspond to enzyme-linked DNA breaks (for a review see Pommier, 1996). Camptothecin induces replication-dependent DNA lesions, and arrests cells in the S and G2 phase of the cell cycle.
What is the mechanism of action of camptothecin?
The primary mechanism of cell killing by CPT is S-phase-specific killing through potentially lethal collisions between advancing replication forks and topo-I cleavable complexes.
How do drugs induce apoptosis?
Factors that were critical in drug-induced apoptosis were activation of caspases, with caspase-8 being activated by diverse drugs in a FADD-independent manner. Certain drugs also demonstrated some dependence on FADD in the induction of cell death. Caspase-9 was activated more selectively by chemotherapeutic agents.Feb 25, 2002
Do drugs cause apoptosis?
Most of the cytotoxic anticancer drugs in current use have been shown to induce apoptosis in susceptible cells.
How can apoptosis be induced?
Induction Overview
In cell lines intrinsic apoptosis can be induced by stimuli including removing growth factor supplements from cell media, exposure to UV light or by exerting other stressful conditions on the cell as shown on the left of Figure 1.
How does chemotherapy induce apoptosis?
Several reports have suggested that anticancer drugs kill susceptible cells by inducing expression of death receptor ligands, especially Fas ligand (FasL). Other reports have indicated that chemotherapeutic agents trigger apoptosis by inducing release of cytochrome c from mitochondria.Apr 10, 2000