Limits...
A novel synthetic analog of 5, 8-disubstituted quinazolines blocks mitosis and induces apoptosis of tumor cells by inhibiting microtubule polymerization.

Tian W, Qin L, Song Q, He L, Ai M, Jin Y, Zhou Z, You S, Long Y, Yu Q - PLoS ONE (2010)

Bottom Line: Tremendous efforts have been made to identify new anti-mitosis compounds for developing more effective and less toxic anti-cancer drugs.In addition, LJK-11 had synergistic effect with another microtubule inhibitor colchicine on blocking mitosis, but not with vinblastine or nocodazole.Understanding the function and mechanism of LJK-11 will help us to better understand the action of anti-microtubule agents and to design better anti-cancer drugs.

View Article: PubMed Central - PubMed

Affiliation: The School of Life Science and Biopharmaceutics of Shenyang Pharmaceutical University, Liaoning, China.

ABSTRACT
Many mitosis inhibitors are powerful anticancer drugs. Tremendous efforts have been made to identify new anti-mitosis compounds for developing more effective and less toxic anti-cancer drugs. We have identified LJK-11, a synthetic analog of 5, 8-disubstituted quinazolines, as a novel mitotic blocker. LJK-11 inhibited growth and induced apoptosis of many different types of tumor cells. It prevented mitotic spindle formation and arrested cells at early phase of mitosis. Detailed in vitro analysis demonstrated that LJK-11 inhibited microtubule polymerization. In addition, LJK-11 had synergistic effect with another microtubule inhibitor colchicine on blocking mitosis, but not with vinblastine or nocodazole. Therefore, LJK-11 represents a novel anti-microtubule structure. Understanding the function and mechanism of LJK-11 will help us to better understand the action of anti-microtubule agents and to design better anti-cancer drugs.

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Related in: MedlinePlus

Effects of LJK-11 on cell cycle distribution.A. Flow cytometry analysis of LJK-11-treated A549 tumor cells. A549 cells were incubated with different concentrations of LJK-11 for 24 hours. The cells were then fixed and stained with PI, and analyzed by flow cytometry. B. Percentage of cells in G2/M phase after 24 hours treatment with different concentrations of LJK-11. The data are the means of triplicates ±SD. C. Flow cytometry analysis of LJK-11-treated MDA-MB-453 tumor cells. MDA-MB-453 cells were incubated with different concentrations of LJK-11 for 24 hours. The cells were then fixed and stained with PI, and analyzed by flow cytometry. D. Percentage of cells in G2/M phase after 24 hours treatment with different concentrations of LJK-11. The data are the representative of three independent experiments.
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pone-0010499-g005: Effects of LJK-11 on cell cycle distribution.A. Flow cytometry analysis of LJK-11-treated A549 tumor cells. A549 cells were incubated with different concentrations of LJK-11 for 24 hours. The cells were then fixed and stained with PI, and analyzed by flow cytometry. B. Percentage of cells in G2/M phase after 24 hours treatment with different concentrations of LJK-11. The data are the means of triplicates ±SD. C. Flow cytometry analysis of LJK-11-treated MDA-MB-453 tumor cells. MDA-MB-453 cells were incubated with different concentrations of LJK-11 for 24 hours. The cells were then fixed and stained with PI, and analyzed by flow cytometry. D. Percentage of cells in G2/M phase after 24 hours treatment with different concentrations of LJK-11. The data are the representative of three independent experiments.

Mentions: We observed gradual accumulation of rounded cells, which resemble the appearance of mitotic cells, after addition of LJK-11. We therefore analyzed the effect of LJK-11 on cell cycle[21]. LJK-11 induced a dose-dependent G2/M arrest after 24 hours of drug exposure. 88% of the cell population was blocked in G2/M phase when they were exposed to 50 µM LJK-11 for 24 hours (Fig. 5A and B).


A novel synthetic analog of 5, 8-disubstituted quinazolines blocks mitosis and induces apoptosis of tumor cells by inhibiting microtubule polymerization.

Tian W, Qin L, Song Q, He L, Ai M, Jin Y, Zhou Z, You S, Long Y, Yu Q - PLoS ONE (2010)

Effects of LJK-11 on cell cycle distribution.A. Flow cytometry analysis of LJK-11-treated A549 tumor cells. A549 cells were incubated with different concentrations of LJK-11 for 24 hours. The cells were then fixed and stained with PI, and analyzed by flow cytometry. B. Percentage of cells in G2/M phase after 24 hours treatment with different concentrations of LJK-11. The data are the means of triplicates ±SD. C. Flow cytometry analysis of LJK-11-treated MDA-MB-453 tumor cells. MDA-MB-453 cells were incubated with different concentrations of LJK-11 for 24 hours. The cells were then fixed and stained with PI, and analyzed by flow cytometry. D. Percentage of cells in G2/M phase after 24 hours treatment with different concentrations of LJK-11. The data are the representative of three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864768&req=5

pone-0010499-g005: Effects of LJK-11 on cell cycle distribution.A. Flow cytometry analysis of LJK-11-treated A549 tumor cells. A549 cells were incubated with different concentrations of LJK-11 for 24 hours. The cells were then fixed and stained with PI, and analyzed by flow cytometry. B. Percentage of cells in G2/M phase after 24 hours treatment with different concentrations of LJK-11. The data are the means of triplicates ±SD. C. Flow cytometry analysis of LJK-11-treated MDA-MB-453 tumor cells. MDA-MB-453 cells were incubated with different concentrations of LJK-11 for 24 hours. The cells were then fixed and stained with PI, and analyzed by flow cytometry. D. Percentage of cells in G2/M phase after 24 hours treatment with different concentrations of LJK-11. The data are the representative of three independent experiments.
Mentions: We observed gradual accumulation of rounded cells, which resemble the appearance of mitotic cells, after addition of LJK-11. We therefore analyzed the effect of LJK-11 on cell cycle[21]. LJK-11 induced a dose-dependent G2/M arrest after 24 hours of drug exposure. 88% of the cell population was blocked in G2/M phase when they were exposed to 50 µM LJK-11 for 24 hours (Fig. 5A and B).

Bottom Line: Tremendous efforts have been made to identify new anti-mitosis compounds for developing more effective and less toxic anti-cancer drugs.In addition, LJK-11 had synergistic effect with another microtubule inhibitor colchicine on blocking mitosis, but not with vinblastine or nocodazole.Understanding the function and mechanism of LJK-11 will help us to better understand the action of anti-microtubule agents and to design better anti-cancer drugs.

View Article: PubMed Central - PubMed

Affiliation: The School of Life Science and Biopharmaceutics of Shenyang Pharmaceutical University, Liaoning, China.

ABSTRACT
Many mitosis inhibitors are powerful anticancer drugs. Tremendous efforts have been made to identify new anti-mitosis compounds for developing more effective and less toxic anti-cancer drugs. We have identified LJK-11, a synthetic analog of 5, 8-disubstituted quinazolines, as a novel mitotic blocker. LJK-11 inhibited growth and induced apoptosis of many different types of tumor cells. It prevented mitotic spindle formation and arrested cells at early phase of mitosis. Detailed in vitro analysis demonstrated that LJK-11 inhibited microtubule polymerization. In addition, LJK-11 had synergistic effect with another microtubule inhibitor colchicine on blocking mitosis, but not with vinblastine or nocodazole. Therefore, LJK-11 represents a novel anti-microtubule structure. Understanding the function and mechanism of LJK-11 will help us to better understand the action of anti-microtubule agents and to design better anti-cancer drugs.

Show MeSH
Related in: MedlinePlus