Cisplatin stops tubulin assembly into microtubules. A new insight into the mechanism of antitumor activity of platinum complexes

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Cisplatin stops tubulin assembly into microtubules. A new insight into the mechanism of antitumor activity of platinum complexes. / Tulub, Alexander A.; Stefanov, Vasily E.

In: International Journal of Biological Macromolecules, Vol. 28, No. 3, 13.03.2001, p. 191-198.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{b95959128241495eb299717668d8eaa7,

title = "Cisplatin stops tubulin assembly into microtubules. A new insight into the mechanism of antitumor activity of platinum complexes",

abstract = "Despite numerous studies considering DNA as a primary target of cisplatin attack, this work is the first to show the pure effect of cisplatin on the process of tubulin assembly/disassembly in vitro. When platinated, tubulin does not assemble into microtubules (direct electron microscopic studies). In place of them, highly stable and inert circled rings arise. Such tubulin aggregates are unable to participate in the process of chromosome separation during the mitosis, thus blocking cell division in living cells, which is a direct evidence of cisplatin antitumor activity. Cisplatin attack on tubulin causing blockage of tubulin assembly occurs via a two-step binding to GTP in the GTP center of tubulin (195Pt, 31P NMR studies). The calculated binding rates are close to those reported in cisplatin-DNA interactions. The mechanism of cisplatin attack on tubulin is proposed.",

keywords = "Assembly/disassembly, Cisplatin, Tubulin",

author = "Tulub, {Alexander A.} and Stefanov, {Vasily E.}",

note = "Funding Information: We are grateful to Dr V. Milligan and Dr E. Bauer for permanent assistance in our work. The authors are also very grateful to Professor Donowan and the group of Professor A. Madariaga from Barcelona University for useful discussions. The work is supported by a research grant from the Russian Foundation for Basic Research (RFFI) 99-04-49836 and NATO Ecology Program.",

year = "2001",

month = mar,

day = "13",

doi = "10.1016/S0141-8130(00)00159-8",

language = "English",

volume = "28",

pages = "191--198",

journal = "International Journal of Biological Macromolecules",

issn = "0141-8130",

publisher = "Elsevier",

number = "3",

}

RIS

TY - JOUR

T1 - Cisplatin stops tubulin assembly into microtubules. A new insight into the mechanism of antitumor activity of platinum complexes

AU - Tulub, Alexander A.

AU - Stefanov, Vasily E.

N1 - Funding Information: We are grateful to Dr V. Milligan and Dr E. Bauer for permanent assistance in our work. The authors are also very grateful to Professor Donowan and the group of Professor A. Madariaga from Barcelona University for useful discussions. The work is supported by a research grant from the Russian Foundation for Basic Research (RFFI) 99-04-49836 and NATO Ecology Program.

PY - 2001/3/13

Y1 - 2001/3/13

N2 - Despite numerous studies considering DNA as a primary target of cisplatin attack, this work is the first to show the pure effect of cisplatin on the process of tubulin assembly/disassembly in vitro. When platinated, tubulin does not assemble into microtubules (direct electron microscopic studies). In place of them, highly stable and inert circled rings arise. Such tubulin aggregates are unable to participate in the process of chromosome separation during the mitosis, thus blocking cell division in living cells, which is a direct evidence of cisplatin antitumor activity. Cisplatin attack on tubulin causing blockage of tubulin assembly occurs via a two-step binding to GTP in the GTP center of tubulin (195Pt, 31P NMR studies). The calculated binding rates are close to those reported in cisplatin-DNA interactions. The mechanism of cisplatin attack on tubulin is proposed.

AB - Despite numerous studies considering DNA as a primary target of cisplatin attack, this work is the first to show the pure effect of cisplatin on the process of tubulin assembly/disassembly in vitro. When platinated, tubulin does not assemble into microtubules (direct electron microscopic studies). In place of them, highly stable and inert circled rings arise. Such tubulin aggregates are unable to participate in the process of chromosome separation during the mitosis, thus blocking cell division in living cells, which is a direct evidence of cisplatin antitumor activity. Cisplatin attack on tubulin causing blockage of tubulin assembly occurs via a two-step binding to GTP in the GTP center of tubulin (195Pt, 31P NMR studies). The calculated binding rates are close to those reported in cisplatin-DNA interactions. The mechanism of cisplatin attack on tubulin is proposed.

KW - Assembly/disassembly

KW - Cisplatin

KW - Tubulin

UR - http://www.scopus.com/inward/record.url?scp=0035852967&partnerID=8YFLogxK

U2 - 10.1016/S0141-8130(00)00159-8

DO - 10.1016/S0141-8130(00)00159-8

M3 - Article

C2 - 11251225

AN - SCOPUS:0035852967

VL - 28

SP - 191

EP - 198

JO - International Journal of Biological Macromolecules

JF - International Journal of Biological Macromolecules

SN - 0141-8130

IS - 3

ER -

ID: 89840746