The transport and binding of taxol

Parekh, Hemant; Simpkins, Henry

doi:10.1016/s0306-3623(97)89716-9

Cited by 45 publications

(30 citation statements)

References 29 publications

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“…We have investigated the role of microtubules in the activation of SOCE in HEK-293 cells and the interaction between STIM1, Orai1 and TRPC1 controlled by depletion of the intracellular stores by using colchicine, a tubulin microtubule disrupting agent [29][30], and paclitaxel that induces microtubular stabilization and increases the cellular microtubular content [31][32]. Treatment with 30 µM colchicine for 30 min at 37ºC significantly reduced the microtubular content in non-stimulated cells, as well as abolished tubulin polymerisation after stimulation with 1 µM TG ( 2A).…”

Section: Discussionmentioning

confidence: 99%

The cytoskeleton plays a modulatory role in the association between STIM1 and the Ca2+ channel subunits Orai1 and TRPC1

Galán

Dionisio

Smani

et al. 2011

Biochemical Pharmacology

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Store-operated Ca 2+ entry (SOCE) is a major pathway for Ca 2+ influx in non-excitable cells.Recent studies favour a conformational coupling mechanism between the endoplasmic reticulum (ER) Ca 2+ sensor STIM1 and Ca 2+ permeable channels in the plasma membrane to explain SOCE. Previous studies have reported a role for the cytoskeleton modulating the activation of SOCE; therefore, here we have investigated whether the interaction between STIM1 and the Ca 2+ permeable channels is modulated by the actin or microtubular network.In . Thus, we demonstrate that the cytoskeleton plays an essential role in the regulation of SOCE through the modulation of the interaction between their main molecular components.

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Section: Discussionmentioning

confidence: 99%

The cytoskeleton plays a modulatory role in the association between STIM1 and the Ca2+ channel subunits Orai1 and TRPC1

Galán

Dionisio

Smani

et al. 2011

Biochemical Pharmacology

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“…Several antimicrotubular drugs such as colchicin and Vinca alkaloids are used in treatment of malignant tumors to date (39). One of these drugs that binds to polymeric tubulin and thereby interferes with the microtubular system is paclitaxel (33). Paclitaxel inhibits disassembly of microtubules, whereas most other known antimicrotubule drugs inhibit microtubule assembly.…”

Section: Discussionmentioning

confidence: 99%

“…Paclitaxel, a common drug that interferes with microtubules, was used as a tool to block microtubular transport function. Paclitaxel binds to the ␤-tubulin subunit of polymerized tubulin tubes and inhibits depolymerization of those tubes (33). Moreover, it is well known that paclitaxel interferes with the mitotic spindle and therefore inhibits cell proliferation (34,35).…”

Section: Matrix Metalloproteinase-2 Is Stored and Transported In Smallmentioning

confidence: 99%

Microtubule-Dependent Matrix Metalloproteinase-2/Matrix Metalloproteinase-9 Exocytosis

et al. 2004

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Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that cleave and degrade a wide spectrum of extracellular matrix components. By enhancing turnover of extracellular matrix, MMP activity is also known to play a key role in tumor cell invasion. Because extracellular protease activity requires efficient release of these proteases to the cellular surface, we investigated storage, transport, and exocytosis of MMP-2 and MMP-9 in human melanoma cells using immunofluorescence, electrical, and biochemical techniques. Immunolabeling of melanoma cells with antibodies specific for MMP-2 and MMP-9 led to the identification of two distinct populations of small cytoplasmatic vesicles containing MMP-2 or MMP-9, respectively. In combination with ␣-tubulin-specific antibodies, both vesicle populations were found to be aligned along the microtubular network. Moreover, the molecular motor protein kinesin is shown to be localized on most of these vesicles, providing evidence that the identified vesicles are actively propelled along microtubules toward the plasma membrane. The functional relevance of these findings is demonstrated using low dosage (5.9 nmol/L) of paclitaxel to affect the microtubular function of melanoma cells. Although cell proliferation is not altered, paclitaxel treatment impairs secretion of MMP-2/MMP-9 and significantly reduces invasive activity in our new cell invasion assay. In conclusion, we demonstrate in melanoma cells that microtubule-dependent traffic of MMP-containing vesicles and exocytosis are critical steps for invasive behavior and therefore are potential targets for specific antitumor drugs.

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“…Paclitaxel did not prevent mitotic arrest. Paclitaxel alone can tightly bind to the microtubules of A. nidulans and promote the formation of highly stable microtubules, thereby preventing cell division in mitosis (33,44). Treatment with paclitaxel was able to cause the formation of extremely stable microtubules in accordance with the characteristics of the benA33 mutant.…”

mentioning

confidence: 97%

“…Vinca alkaloids such as vinblastine and vincristine, which are anticancer drugs isolated from plants, inhibit microtubule assembly (14,32). Paclitaxel (taxol), which is also an anticancer drug isolated from a plant, binds to the N-terminal region of ␤-tubulin and promotes the formation of highly stable microtubules that resist depolymerization (33). Ansamitocin P-3 and rhizoxin are macrocyclic antitumor antibiotics, isolated as a cytotoxic metabolite of an actinomycete and as a phytotoxin produced by a plant-pathogenic fungus, respectively (14).…”

mentioning

confidence: 99%

Screening for Microtubule-Disrupting Antifungal Agents by Using a Mitotic-Arrest Mutant of Aspergillus nidulans and Novel Action of Phenylalanine Derivatives Accompanying Tubulin Loss

Kiso

Fujita

et al. 2004

Antimicrob Agents Chemother

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The microtubule, which is one of the major targets of anthelmintics, anticancer drugs, and fungicides, is composed mainly of ␣-and ␤-tubulins. We focused on a unique characteristic of an Aspergillus nidulans benA33 mutant to screen for microtubule-disrupting antifungal agents. This mutant, which has a ␤-tubulin with a mutation of a single amino acid, undergoes mitotic arrest due to the formation of hyperstable microtubules at 37°C. The heat sensitivity of the mutant is remedied by some antimicrotubule agents. We found that an agar plate assay with the mutant was able to distinguish three types of microtubule inhibitors. The growth recovery zones of the mutant were formed around paper disks containing microtubule inhibitors, including four benzimidazoles, ansamitocin P-3, griseofulvin, and rhizoxin, on the agar plate at 37°C. Nocodazole, thiabendazole, and griseofulvin reversed the mitotic arrest of the mutant and promoted its hyphal growth. Ansamitocin P-3 and rhizoxin showed growth recovery zones around the growth-inhibitory zones. Benomyl and carbendazim also reversed mitotic arrest but produced weaker growth recovery than the aforementioned drugs. Other microtubule inhibitors, such as colchicine, Colcemid, paclitaxel, podophyllotoxin, TN-16, vinblastine, and vincristine, as well as some cytoskeletal inhibitors tested, did not show such activity. In our screening, we newly identified two mycotoxins, citrinin and patulin, two sesquiterpene dialdehydes, polygodial and warburganal, and four phenylalanine derivatives, arphamenine A, L-2,5-dihydrophenylalanine (DHPA), N-tosyl-L-phenylalanine chloromethylketone, and N-carbobenzoxy-L-phenylalanine chloromethyl ketone. In a wild-type strain of A. nidulans, DHPA caused selective losses of microtubules, as determined by fluorescence microscopy, and of both ␣-and ␤-tubulins, as determined by Western blot analysis. This screening method involving the benA33 mutant of A. nidulans is useful, convenient, and highly selective. The phenylalanine derivatives tested are of a novel type of microtubule-disrupting antifungal agents, producing an accompanying loss of tubulins, and are different from well-known tubulin inhibitors affecting the assembly of tubulin dimers into microtubules.

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The transport and binding of taxol

Cited by 45 publications

References 29 publications

The cytoskeleton plays a modulatory role in the association between STIM1 and the Ca2+ channel subunits Orai1 and TRPC1

The cytoskeleton plays a modulatory role in the association between STIM1 and the Ca2+ channel subunits Orai1 and TRPC1

Microtubule-Dependent Matrix Metalloproteinase-2/Matrix Metalloproteinase-9 Exocytosis

Screening for Microtubule-Disrupting Antifungal Agents by Using a Mitotic-Arrest Mutant of Aspergillus nidulans and Novel Action of Phenylalanine Derivatives Accompanying Tubulin Loss

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