Antiviral Action of Camptothecin

Horwitz, Susan Band; Chang, Chung-Ke; Grollman, Arthur P.

doi:10.1128/aac.2.5.395

Cited by 28 publications

(15 citation statements)

References 17 publications

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“…A role of the poxvirus topoisomerase in homologous DNA recombination is also unlikely on the grounds that late gene expression is not required (28,35). Our experiments do not exclude a role for a cellular topoisomerase in transcription or replication, and the inhibition of vaccinia virus RNA and DNA synthesis by camptothecin, a specific inhibitor of cellular topoisomerase, has been reported (36).…”

Section: Discussionmentioning

confidence: 95%

Poxvirus DNA topoisomerase knockout mutant exhibits decreased infectivity associated with reduced early transcription

Fonseca

Moss

2003

Proc. Natl. Acad. Sci. U.S.A.

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Vaccinia virus encodes a type I DNA topoisomerase that is highly conserved in all known poxviruses. Although the structure and catalytic activity of the enzyme were well studied, little was known about its biological function. The viral topoisomerase was thought to be essential, and roles in DNA replication, recombination, concatemer resolution, and transcription were suggested. Here, we demonstrated that the topoisomerase is not essential for replication of vaccinia virus in cultured cells, although deletion mutants formed fewer and smaller plaques on cell monolayers than wild-type virus. Purified mutant virus particles were able to bind and enter cells but exhibited reduced viral early transcription and a delay in DNA replication. Infecting with a high number of virus particles increased early mRNA and accelerated viral DNA synthesis. Processing of viral DNA concatemers into unit-length genomes was unimpaired at either a low or high multiplicity of infection. The data suggest that the primary, perhaps only, role of the poxvirus topoisomerase is to increase early transcription, which takes place within virus cores in the cytoplasm of infected cells. Because the topoisomerase functions early in infection, drugs capable of penetrating the virus core and irreversibly damaging DNA by trapping nicked DNA-topoisomerase intermediates could make potent antiviral agents.

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Section: Discussionmentioning

confidence: 95%

Poxvirus DNA topoisomerase knockout mutant exhibits decreased infectivity associated with reduced early transcription

Fonseca

Moss

2003

Proc. Natl. Acad. Sci. U.S.A.

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“…Results indicated that CPT inhibited DNA synthesis in HeLa cells at a concentration of 10 μM. Inhibition of viral DNA synthesis was observed when CPT was added 1 or 2 hr after infection . Priel et al reported that noncytotoxic doses of CPT inhibited HIV replication in acute infection of H9 cells at a high efficacy (>90%).…”

Section: Biological Activity Of Cpt and Related Derivativesmentioning

confidence: 99%

“…Inhibition of viral DNA synthesis was observed when CPT was added 1 or 2 hr after infection. 89 Priel et al 90 reported that noncytotoxic doses of CPT inhibited HIV replication in acute infection of H9 cells at a high efficacy (>90%). Moreover, CPT inhibited equine infectious anemia virus (EIAV) replication in chronically infected Cf2Th cells.…”

Section: B Antiviral Activitymentioning

confidence: 99%

Perspectives on Biologically Active Camptothecin Derivatives

et al. 2015

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Camptothecins (CPTs) are cytotoxic natural alkaloids that specifically target DNA topoisomerase I. Research on CPTs has undergone a significant evolution from the initial discovery of CPT in the late 1960s through the study of synthetic small molecule derivatives to investigation of macromolecular constructs and formulations. Over the past years, intensive medicinal chemistry efforts have generated numerous CPT derivatives. Three derivatives, topotecan, irinotecan, and belotecan, are currently prescribed as anticancer drugs, and several related compounds are now in clinical trials. Interest in other biological effects, besides anticancer activity, of CPTs is also growing exponentially, as indicated by the large number of publications on the subject during the last decades. Therefore, the main focus of the present review is to provide an ample but condensed overview on various biological activities of CPT derivatives, in addition to continued up-to-date coverage of anticancer effects.

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“…This remarkable achievement was published in 1966 in the Journal of the American Chemical Society, the first paper Wall, Wani and colleagues published on a natural product with anticancer potential [6]. [17,18] and others have established that the synthesis of macromolecules such as RNA, DNA and protein are inhibited by camptothecin in tumor or dividing mammalian cells. The inhibition over DNA synthesis was transient when the drug is removed.…”

Section: Camptothecinmentioning

confidence: 99%

Camptothecin-Discovery, Clinical Perspectives and Biotechnology

2015

Nat Prod Chem Res 2015

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A historical account on discovery of camptothecin In 1955, National Cancer Institute (NCI) created a Cancer Chemotherapy National Service Center (CCNSC) for the evaluation for anticancer efficacy of potential compounds submitted by drug companies and institutions. Initially, CCNSC was screening chemically known structures and by 1960 they started to screen natural products of unknown chemical ingredients from plant and animal origin. The NCI plant program was led by Jonathan Hartwell, an eminent organic chemist, and he later compiled the documents of traditional use of plants to treat cancer from ancient forms of medical practices from Egypt, China, Greece and Rome [9-12]. The United States Department of Agriculture (USDA) was providing plants to NCI for anticancer screening. At Wisconsin Alumni Research Foundation, the plants were extracted and sent to different laboratories to evaluate their potential to kill cancer cells. The samples were initially screened for their cytotoxic effects in KB (oral epidermoid carcinoma) cell culture, a cell line from a human cancer. They were also tested in three tumor xenograft mouse models for S-180, a sarcoma; CA-755, an adenocarcinoma; and L1210, a lymphoid leukemia. Those crude extracts showed anticancer properties were then fractionated for isolating the active compounds at three different laboratories. One among them was newly established Research Triangle Institute (RTI), North Carolina. Manroe E. Wall was leading the Natural Product Laboratory in RTI. Of thousand ethanolic plant extracts screened by NCI for anticancer efficacy, extract of Camptotheca acuminata, a tree

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Antiviral Action of Camptothecin

Cited by 28 publications

References 17 publications

Poxvirus DNA topoisomerase knockout mutant exhibits decreased infectivity associated with reduced early transcription

Poxvirus DNA topoisomerase knockout mutant exhibits decreased infectivity associated with reduced early transcription

Perspectives on Biologically Active Camptothecin Derivatives

Camptothecin-Discovery, Clinical Perspectives and Biotechnology

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