Mechanism of Action of Camptothecin

Liu, Leroy F.; Duann, Pu; Lin, Ching-Tai; D’Arpa, Peter; Wu, Jiaxi

doi:10.1111/j.1749-6632.1996.tb26375.x

Cited by 247 publications

(115 citation statements)

References 4 publications

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“…Paclitaxel stabilizes microtubules and leads to mitotic arrest [109]. In addition, the camptothecin derivatives irinotecan and topotecan have shown significant antitumor activity against colorectal and ovarian cancer, respectively [100, 110], by inhibiting topoisomerase I [111]. Despite the above development, the unequal distribution of cancer burden between the developing and developed world is still largely looking for a better and safer anticancer compound for human use.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Emerging Anticancer Potentials of Goniothalamin and Its Molecular Mechanisms

Ali-Seyed

Jantan

Bukhari

2014

BioMed Research International

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The treatment of most cancers is still inadequate, despite tremendous steady progress in drug discovery and effective prevention. Nature is an attractive source of new therapeutics. Several medicinal plants and their biomarkers have been widely used for the treatment of cancer with less known scientific basis of their functioning. Although a wide array of plant derived active metabolites play a role in the prevention and treatment of cancer, more extensive scientific evaluation of their mechanisms is still required. Styryl-lactones are a group of secondary metabolites ubiquitous in the genus Goniothalamus that have demonstrated to possess antiproliferative activity against cancer cells. A large body of evidence suggests that this activity is associated with the induction of apoptosis in target cells. In an effort to promote further research on the genus Goniothalamus, this review offers a broad analysis of the current knowledge on Goniothalamin (GTN) or 5, 6, dihydro-6-styryl-2-pyronone (C13H12O2), a natural occurring styryl-lactone. Therefore, it includes (i) the source of GTN and other metabolites; (ii) isolation, purification, and (iii) the molecular mechanisms of actions of GTN, especially the anticancer properties, and summarizes the role of GTN which is crucial for drug design, development, and application in future for well-being of humans.

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Section: Mechanism Of Actionmentioning

confidence: 99%

Emerging Anticancer Potentials of Goniothalamin and Its Molecular Mechanisms

Ali-Seyed

Jantan

Bukhari

2014

BioMed Research International

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“…CPT is commonly used as a DNA topo I inhibitor to induce DNA double strand breaks (Liu et al 2000). CPT induces significant DDR in SH-SY5Y cells as early as 1 hour (Wang 2013).…”

Section: Resultsmentioning

confidence: 99%

Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells

et al. 2015

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DNA damage is a form of cell stress and injury. Increased systemic DNA damage is related to the pathogenic development of neurodegenerative diseases. Depression occurs in a relatively high percentage of patients suffering from degenerative diseases, for whom antidepressants are often used to relieve depressive symptoms. However, few studies have attempted to elucidate why different groups of antidepressants have similar effects on relieving symptoms of depression. Previously, we demonstrated that neurotoxins N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)- and camptothecin (CPT)-induced the DNA damage response in SH-SY5Y cells, and DSP4 caused cell cycle arrest which was predominately in the S-phase. The present study shows that CPT treatment also resulted in similar cell cycle arrest. Some classic antidepressants could reduce the DNA damage response induced by DSP4 or CPT in SH-SY5Y cells. Cell viability examination demonstrated that both DSP4 and CPT caused cell death, which was prevented by spontaneous administration of some tested antidepressants. Flow cytometric analysis demonstrated that a majority of the tested antidepressants protect cells from being arrested in S-phase. These results suggest that blocking the DNA damage response may be an important pharmacologic characteristic of antidepressants. Exploring the underlying mechanisms may allow for advances in the effort to improve therapeutic strategies for depression appearing in degenerative and psychiatric diseases.

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“…CPT causes type I topoisomerase-mediated single-strand nicks that lead to replication fork collapse (54,55). We investigated genetic interactions between recombination repair genes in the repair of CPT-induced DNA damage.…”

Section: Resultsmentioning

confidence: 99%

“…The topoisomerase I inhibitor CPT inhibits topoisomerase I leading to single-strand nicks and eventual replication fork collapse (54,55). The sensitivity of mus-50 mutants to CPT indicates that MUS50 promotes the repair of CPT-induced collapsed replication forks.…”

Section: Discussionmentioning

confidence: 99%

Srs2 and RecQ homologs cooperate in mei-3-mediated homologous recombination repair of Neurospora crassa

Suzuki

Sakuraba

Inoue

2005

Nucleic Acids Research

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Homologous recombination and post-replication repair facilitate restart of stalled or collapsed replication forks. The SRS2 gene of Saccharomyces cerevisiae encodes a 3′–5′ DNA helicase that functions both in homologous recombination repair and in post-replication repair. This study identifies and characterizes the SRS2 homolog in Neurospora crassa, which we call mus-50. A knockout mutant of N.crassa, mus-50, is sensitive to several DNA-damaging agents and genetic analyses indicate that it is epistatic with mei-3 (RAD51 homolog), mus-11 (RAD52 homolog), mus-48 (RAD55 homolog) and mus-49 (RAD57 homolog), suggesting a role for mus-50 in homologous recombination repair. However, epistasis evidence has presented that MUS50 does not participate in post-replication repair in N.crassa. Also, the N.crassa mus-25 (RAD54 homolog) mus-50 double mutant is viable, which is in contrast to the lethal phenotype of the equivalent rad54 srs2 mutant in S.cerevisiae. Tetrad analysis revealed that mus-50 in combination with mutations in two RecQ homologs, qde-3 and recQ2, is lethal, and this lethality is suppressed by mutation in mei-3, mus-11 or mus-25. Evidence is also presented for the two independent pathways for recovery from camptothecin-induced replication fork arrest: one pathway is dependent on QDE3 and MUS50 and the other pathway is dependent on MUS25 and RECQ2.

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Mechanism of Action of Camptothecin

Cited by 247 publications

References 4 publications

Emerging Anticancer Potentials of Goniothalamin and Its Molecular Mechanisms

Emerging Anticancer Potentials of Goniothalamin and Its Molecular Mechanisms

Effects of Antidepressants on DSP4/CPT-Induced DNA Damage Response in Neuroblastoma SH-SY5Y Cells

Srs2 and RecQ homologs cooperate in mei-3-mediated homologous recombination repair of Neurospora crassa

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