Colchicine Induces Apoptosis in Cerebellar Granule Cells

Bonfoco, Emanuela; Ceccatelli, Sandra; Manzo, Luigi; Nicotera, Pierluigi

doi:10.1006/excr.1995.1147

Cited by 137 publications

(93 citation statements)

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“…Colchicine is a microtubule disrupting drug (TsU-KIDATE et al, 1993;BONFOCO et al, 1995) which induces apoptosis in different cell types, e. g. hepatocytes (TSUKIDATE et al, 1993) and cerebellar granule cells (BONFOCO et al, 1995). Colchicine administration in the present study appears to have induced similar changes, as apoptotic amoeboid microglial cells labelled with the TUNEL method and showing OX-42 immunoreactivity were observed in the present study.…”

Section: Discussionsupporting

confidence: 80%

Effects of Colchicine on Amoeboid Microglial Cells in the Postnatal Rat Brain.

Kaur

1997

Archives of Histology and Cytology

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Section: Discussionsupporting

confidence: 80%

Effects of Colchicine on Amoeboid Microglial Cells in the Postnatal Rat Brain.

Kaur

1997

Archives of Histology and Cytology

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“…Colchicine binds to tubulin with high affinity but has slow binding kinetics and the interaction is poorly reversible. It is an efficient cytotoxic agent and apoptosis inducer (44), but its therapeutic use has been hampered because of high toxicity (6). The toxicity can be attributed to its slow removal from the cell due to very slow dissociation.…”

Section: Discussionmentioning

confidence: 99%

Reversible Action of Diaminothiazoles in Cancer Cells Is Implicated by the Induction of a Fast Conformational Change of Tubulin and Suppression of Microtubule Dynamics

Thomas¹,

Thamkachy²,

Sivakumar³

et al. 2014

Molecular Cancer Therapeutics

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Diaminothiazoles are novel cytotoxic compounds that have shown efficacy toward different cancer cell lines. They show potent antimitotic and antiangiogenic activity upon binding to the colchicine-binding site of tubulin. However, the mechanism of action of diaminothiazoles at the molecular level is not known. Here, we show a reversible binding to tubulin with a fast conformational change that allows the lead diaminothiazole DAT1 [4-amino-5-benzoyl-2-(4-methoxy phenyl amino)thiazole] to cause a reversible mitotic block. DAT1 also suppresses microtubule dynamic instability at much lower concentration than its IC 50 value in cancer cells. Both growth and shortening events were reduced by DAT1 in a concentration-dependent way. Colchicine, the long-studied tubulin-binding drug, has previously failed in the treatment of cancer due to its toxicity, even though it generates a strong apoptotic response. The toxicity is attributable to its slow removal from the cell due to irreversible tubulin binding caused by a slow conformational change. DAT1 binds to tubulin at an optimal pH lower than colchicine. Tubulin conformational studies showed that the binding environments of DAT1 and colchicine are different. Molecular dynamic simulations showed a difference in the number of H-bonding interactions that accounts for the different pH optima. This study gives an insight of the action of compounds targeting tubulin's colchicine-binding site, as many such compounds have entered into clinical trials recently.

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“…After exposure, cells seeded on coverslips were fixed, washed and subsequently stained with propidium iodide as described earlier (Bonfoco et al, 1995). Coverslips were examined either with a Zeiss, Axiovert 135 M confocal laser scanning microscope or with a Leitz fluorescence microscope.…”

Section: Assay For Induction Of Apoptosismentioning

confidence: 99%

Apoptosis is induced in both drug-sensitive and multidrug-resistant hepatoma cells by somatostatin analogue TT-232

et al. 1999

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Clinical resistance to chemotherapeutic drugs is an important problem in the treatment of cancer; the circumvention of resistance has become one of the basic goals of cancer therapy. The most frequent form of primary liver cancer is hepatocellular carcinoma, which is essentially refractory to chemotherapy. We earlier showed that TT-232, a new somatostatin analogue developed in our laboratory, exerted a strong antiproliferative effect both in vitro and in vivo, but no growth hormone release inhibitory or antisecretory activity. Here we report that TT-232 has a pronounced antiproliferative effect on differentiated and dedifferentiated, drug-sensitive and multidrug-resistant hepatocellular carcinoma cell lines. TT-232 induces apoptosis at comparable levels in all these hepatoma variants demonstrating that the multidrug resistance of hepatomas does not correlate with a reduced susceptibility to apoptosis induction. These results clearly reveal that the machinery involved in apoptosis is functional in both drug-sensitive and resistant hepatoma variants and can be activated by the somatostatin analogue TT-232. © 1999 Cancer Research Campaign

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Colchicine Induces Apoptosis in Cerebellar Granule Cells

Cited by 137 publications

References 0 publications

Effects of Colchicine on Amoeboid Microglial Cells in the Postnatal Rat Brain.

Effects of Colchicine on Amoeboid Microglial Cells in the Postnatal Rat Brain.

Reversible Action of Diaminothiazoles in Cancer Cells Is Implicated by the Induction of a Fast Conformational Change of Tubulin and Suppression of Microtubule Dynamics

Apoptosis is induced in both drug-sensitive and multidrug-resistant hepatoma cells by somatostatin analogue TT-232

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