Regulation of microtubule dynamic instability

Cassimeris, Lynne

doi:10.1002/cm.970260402

Cited by 110 publications

(64 citation statements)

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“…This enhanced stability may also explain the large increase in average microtubule length. Based upon in vitro experiments, it has been postulated that animal MAPs stimulate the growth of microtubules not by increasing the rate of polymerization but by decreasing disassembly (7,26,27). The dilution experiments showed that disassembly of microtubules was markedly slower in the presence of MAP60, which may therefore stimulate microtubule growth in the same way neuronal MAPs do, that is, by decreasing disassembly.…”

Section: Discussionmentioning

confidence: 99%

A 60-kDa plant microtubule-associated protein promotes the growth and stabilization of neurotubules in vitro

Rutten

Chan

Lloyd

1997

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

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The search for microtubule-associated proteins (MAPs) in plants is relatively recent. In particular, the ''classical MAPs,'' which stimulate the polymerization and stabilization of microtubules, have only been examined in heterogeneous fractions. As a first step in dissecting the role of individual MAPs, we have chromatographically purified a single 60-kDa protein from a carrot MAP fraction and analyzed its effects on tubulin assembly. MAP60 promoted the formation of long, morphologically regular brain microtubules in vitro, an effect inhibited by preincubation of the MAP with affinity-purified antibodies against this protein. MAP60 also increased the stability of microtubules to dilution and significantly enhanced cold stability to the normally coldsensitive neurotubules. These in vitro properties are consistent with a role for MAP60 in regulating the turnover͞assembly of dynamic plant microtubules in vivo.

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Section: Discussionmentioning

confidence: 99%

A 60-kDa plant microtubule-associated protein promotes the growth and stabilization of neurotubules in vitro

Rutten

Chan

Lloyd

1997

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

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Section: Tubulin Polymerization Assaymentioning

confidence: 99%

“…heterodimers formed by α-and β-tubulin proteins. 42,44,45 Due to their essential role during cellular division processes, microtubules are among the most common and effective targets in cancer cells. Recent studies have reported the ability of arylsubstituted piperlongumine analogues to inhibit microtubule polymerization in vitro.…”

Section: Tubulin Polymerization Assaymentioning

confidence: 99%

“…3, 2017 heterodimers formed by α-and β-tubulin proteins. 42,44,45 Due to their essential role during cellular division processes, microtubules are among the most common and effective targets in cancer cells.Recent studies have reported the ability of arylsubstituted piperlongumine analogues to inhibit microtubule polymerization in vitro. 46 However, other independent studies of piperlongumine and similar derivatives have demonstrated substantial anti-inflammatory activity for this class of compounds.…”

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confidence: 99%

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Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration

Valli¹,

Altei²,

Santos³

et al. 2017

J. Braz. Chem. Soc.

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Piperlongumine is a natural amide alkaloid isolated from several species of Piper and is described in the literature as selectively cytotoxic to several cancer cell lines. Inhibiting cell migration has gained considerable interest as an approach for discovering antimetastatic agents because this process is fundamental to metastasis. Piperlongumine, selected from cell-based assay screening of NuBBE Database, inhibited the migration of MDA-MB-231 breast cancer cells with an EC 50 of 3.0 ± 1.0 µM by the Boyden chamber assay. A series of five analogous compounds based on the structure of piperlongumine were designed, synthesized and evaluated in cell migration and cytotoxicity assays. The analogue designed by molecular simplification ((E)-N-acryloyl-3-(3,4,5-trimethoxyphenyl)acrylamide) was the most active of the series, with an EC 50 of 1.5 ± 1 µM. Additionally, this compound was selectively cytotoxic, with a selectivity index (SI) of 4.4. Keywords: piperlongumine, piplartine, piperamide, cytotoxicity, cell migration inhibition IntroductionMetastasis is the process by which undifferentiated cancer cells migrate to other parts of the body.1,2 Suppression of metastasis is an urgent need in cancer treatment, as most existing drugs only inhibit cell proliferation.3 Traditionally, chemotherapy is based on cytotoxic therapeutic agents that inhibit proliferation and cause cell death. However, the strategy of inhibiting cell migration has recently gained considerable interest. 4 Several compounds that inhibit the process of metastasis have been described to date. 5,6 Paclitaxel, which was originally discovered as an antimitotic agent that disrupts the cell cycle in cancer cells by stabilizing microtubules, exhibits marked and selective inhibition of tumor cell migration. 7As extensively reviewed elsewhere, biodiversity in nature has provided unique chemical scaffolds that have been used as templates for medicinal chemistry and drug discovery. [8][9][10][11][12][13] The availability of natural compound libraries is of significant importance for integrating natural products and medicinal chemistry, especially for the identification of new bioactive agents and the rational design of compounds in drug discovery.14 Within this context, we selected the natural product piperlongumine (1), also known as piplartine, from cell-based assay screening of NuBBE Database (NuBBE DB ) 15 and evaluated its ability to inhibit Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration J. Braz. Chem. Soc. 476 cancer cell migration using biological and target-based experiments.Piperlongumine (1, Figure 1) is an alkamide isolated from several species of Piper (Piperaceae). 16 It is described as possessing antifungal properties, 17 cytotoxicity toward several cancer cell lines, 18,19 and trypanocidal effects, 20 as well as other biological activities. 21 Furthermore, piperlongumine selectively induces cell death in cancer cells but does not reduce viability in normal cells. 22This ...

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“…Other factors, such as mitogen-activated proteins (MAPs) and tubulin isotypes, are also involved in the events of microtubule stabilization (Matus, 1988;Falconer et al, 1992). Dynamic instability is cell type-specific (Cassimeris, 1993;Shelden and Wadsworth, 1993). Moreover, the molecular mechanisms responsible for the control of microtubule dynamic behaviour during cell growth and differentiation are largely unknown.…”

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confidence: 99%

Differentiation of human colon cancer cells changes the expression of β-tubulin isotypes and MAPs

et al. 1999

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SummaryThe human colon adenocarcinoma HT29-D4 cell line is an interesting model for studies on epithelial cell differentiation. Undifferentiated cells are malignant proliferating cells, whereas differentiated cells act like epithelial polarized cells. In the present study, we first characterized the action of taxoids on the microtubular network of HT29-D4 cells according to the state of differentiation. Microtubular bundles were found in undifferentiated cells but not in differentiated cells, even with 500-fold higher taxoid concentrations for 96 h. This finding led us to study changes in microtubules according to the polarity status of the cell. E-MAP-115 was expressed only in differentiated cells; expression of β-tubulin isotypes was altered in them relative to undifferentiated cells. Classes I, II, III, IVa and IVb isotypes were expressed in both phenotypes; however, differentiated epithelial cells displayed a specific increase in class III β-tubulin. Thus, the increase in expression of this β-tubulin isotype in differentiated cells is not restricted to neuronal cells. Moreover, these expression changes may reflect a higher stability of microtubular network in differentiated cells, which may explain the lower activity of anti-microtubule agents, independently of the mitotic process. These results indicate that the composition of microtubules should be considered as one of the criteria involved in the response of tumour cells to chemotherapy with anti-microtubule agents.

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Regulation of microtubule dynamic instability

Cited by 110 publications

References 50 publications

A 60-kDa plant microtubule-associated protein promotes the growth and stabilization of neurotubules in vitro

A 60-kDa plant microtubule-associated protein promotes the growth and stabilization of neurotubules in vitro

Synthetic Analogue of the Natural Product Piperlongumine as a Potent Inhibitor of Breast Cancer Cell Line Migration

Differentiation of human colon cancer cells changes the expression of β-tubulin isotypes and MAPs

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