Griseofulvin

Carli, L. De; Larizza, Lidia

doi:10.1016/0165-1110(88)90020-6

Cited by 79 publications

(37 citation statements)

References 141 publications

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“…Griseofulvin, an orally active, nontoxic antifungal drug derived from several species of Penicillium, has been used for many years for the treatment of tinea capitis and other dermatophyte infections (36,37). Early studies showed that griseofulvin inhibits mitosis in sensitive fungi in a manner resembling the actions of colchicine (21).…”

Section: Discussionmentioning

confidence: 99%

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Identification of Griseofulvin as an Inhibitor of Centrosomal Clustering in a Phenotype-Based Screen

Larsen²,

et al. 2007

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A major drawback of cancer chemotherapy is the lack of tumor-specific targets which would allow for the selective eradication of malignant cells without affecting healthy tissues. In contrast with normal cells, most tumor cells contain multiple centrosomes, associated with the formation of multipolar mitotic spindles and chromosome segregation defects. Many tumor cells regain mitotic stability after clonal selection by the coalescence of multiple centrosomes into two functional spindle poles. To overcome the limitations of current cancer treatments, we have developed a cell-based screening strategy to identify small molecules that inhibit centrosomal clustering and thus force tumor cells with supernumerary centrosomes to undergo multipolar mitoses, and subsequently, apoptosis. Using a chemotaxonomic selection of fungi from a large culture collection, a relatively small but diverse natural product extract library was generated. Screening of this compound library led to the identification of griseofulvin, which induced multipolar spindles by inhibition of centrosome coalescence, mitotic arrest, and subsequent cell death in tumor cell lines but not in diploid fibroblasts and keratinocytes with a normal centrosome content. The inhibition of centrosome clustering by griseofulvin was not restricted to mitotic cells but did occur during interphase as well. Whereas the formation of multipolar spindles was dyneinindependent, depolymerization of interphase microtubules seemed to be mechanistically involved in centrosomal declustering. In summary, by taking advantage of the tumorspecific phenotype of centrosomal clustering, we have developed a screening strategy that might lead to the identification of drugs which selectively target tumor cells and spare healthy tissues. [Cancer Res 2007;67(13):6342-50]

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Section: Discussionmentioning

confidence: 99%

“…However, in vitro griseofulvin induces numerous chromosomal aberrations in all the systems analyzed (36). In mice and rats, prolonged treatment with griseofulvin provoked the development of multiple hepatomas (36).…”

Section: Discussionmentioning

confidence: 99%

Identification of Griseofulvin as an Inhibitor of Centrosomal Clustering in a Phenotype-Based Screen

Larsen²,

et al. 2007

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“…Its mechanism of action has been thought to involve the selective inhibition of fungal cell mitosis in association with its accumulation in the keratin layers of the epidermis (1). Early studies demonstrated that griseofulvin inhibits mitosis in sensitive fungi in a manner resembling the actions of colchicine and other antimitotic drugs that act in mammalian cells by disrupting spindle microtubule (MT) function (3), although its precise mechanism of action in sensitive fungi remains unclear.…”

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confidence: 99%

Kinetic suppression of microtubule dynamic instability by griseofulvin: Implications for its possible use in the treatment of cancer

Panda

Rathinasamy

Santra

et al. 2005

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

159

162

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The antifungal drug griseofulvin inhibits mitosis strongly in fungal cells and weakly in mammalian cells by affecting mitotic spindle microtubule (MT) function. Griseofulvin also blocks cell-cycle progression at G2͞M and induces apoptosis in human tumor cell lines. Despite extensive study, the mechanism by which the drug inhibits mitosis in human cells remains unclear. Here, we analyzed the ability of griseofulvin to inhibit cell proliferation and mitosis and to affect MT polymerization and organization in HeLa cells together with its ability to affect MT polymerization and dynamic instability in vitro. Griseofulvin inhibited cell-cycle progression at prometaphase͞anaphase of mitosis in parallel with its ability to inhibit cell proliferation. At its mitotic IC 50 of 20 M, spindles in blocked cells displayed nearly normal quantities of MTs and MT organization similar to spindles blocked by more powerful MTtargeted drugs. Similar to previously published data, we found that very high concentrations of griseofulvin (>100 M) were required to inhibit MT polymerization in vitro. However, much lower drug concentrations (1-20 M) strongly suppressed the dynamic instability behavior of the MTs. We suggest that the primary mechanism by which griseofulvin inhibits mitosis in human cells is by suppressing spindle MT dynamics in a manner qualitatively similar to that of much more powerful antimitotic drugs, including the vinca alkaloids and the taxanes. In view of griseofulvin's lack of significant toxicity in humans, we further suggest that it could be useful as an adjuvant in combination with more powerful drugs for the treatment of cancer.cancer chemotherapy ͉ mitosis

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“…Mitotic segregation is also induced in fungi by G F treatment. In higher eu karyotes, the cytostatic action o l'G F is essentially due to a mitotic arrest at late metaphase early anaphase [4]. G F .…”

Section: Introductionmentioning

confidence: 99%

“…Dietary ex posure to G F produced a significant incidence o f hepa tocellular tumors in mice, thyroid tumors in rats, but no carcinogenic activity in hamsters [12]. G F may also act either as a promoting or a carcinogenic agent, depending on the circumstances o f its administration [4], A cocarcinogenic effect on skin tumor development in mice was noted when G F was administered orally before, during or after topical treatment with methylcholanthrene [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Induction of Hepatocellular Carcinomas in the Egyptian Toad <i>Bufo regularis</i> by an Antifungal Drug (Griseofulvin)

1993

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Griseofulvin

Cited by 79 publications

References 141 publications

Identification of Griseofulvin as an Inhibitor of Centrosomal Clustering in a Phenotype-Based Screen

Identification of Griseofulvin as an Inhibitor of Centrosomal Clustering in a Phenotype-Based Screen

Kinetic suppression of microtubule dynamic instability by griseofulvin: Implications for its possible use in the treatment of cancer

Induction of Hepatocellular Carcinomas in the Egyptian Toad <i>Bufo regularis</i> by an Antifungal Drug (Griseofulvin)

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