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Jong-soo Chang - One of the best experts on this subject based on the ideXlab platform.

  • The Colchicine Derivative CT20126 shows a novel microtubule-modulating activity with apoptosis.
    Experimental & molecular medicine, 2013
    Co-Authors: Sung-kuk Kim, Heon Seok, Sang-min Cho, Ho Kim, Soon-ok Kim, Taeg Kyu Kwon, Jong-soo Chang
    Abstract:

    New Colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 μM), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of Colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of Colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than Colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 nM, CT20126 induced 47% apoptosis among Jurkat T cells, whereas Colchicine induced only 33% apoptosis. Our results suggest that the Colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of Colchicine or Taxol.

  • The Colchicine Derivative CT20126 shows a novel microtubule-modulating activity with apoptosis
    Experimental & Molecular Medicine, 2013
    Co-Authors: Heon Seok, Taeg Kyu Kwon, Jong-soo Chang
    Abstract:

    Colchicine's value as an anticancer drug is undercut by harmful side effects, but a related compound may offer a useful alternative. Cell division is facilitated by dynamic assembly and disassembly of tubulin protein into microtubule filaments, which ensure that each new cell receives a full set of chromosomes. Colchicine thwarts cancerous growth by forcing microtubule disassembly. Since it can also be toxic to patients, Jong-Soo Chang of Korea's Daejin University and colleagues characterized the anticancer effects of a Colchicine Derivative called CT20126. Unlike Colchicine, CT20126 only transiently stimulates microtubule disassembly, and subsequently promotes aggregation of tubulin into unusually short, thick filaments. Nevertheless, CT20126 still proved a potent inhibitor of proliferation in cultured human cells, and triggered programmed cell death more efficiently than other microtubule-targeting drugs, highlighting its potential as a therapeutic candidate. New Colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 μ M ), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of Colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of Colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than Colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 n M , CT20126 induced 47% apoptosis among Jurkat T cells, whereas Colchicine induced only 33% apoptosis. Our results suggest that the Colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of Colchicine or Taxol.

Heon Seok - One of the best experts on this subject based on the ideXlab platform.

  • The Colchicine Derivative CT20126 shows a novel microtubule-modulating activity with apoptosis.
    Experimental & molecular medicine, 2013
    Co-Authors: Sung-kuk Kim, Heon Seok, Sang-min Cho, Ho Kim, Soon-ok Kim, Taeg Kyu Kwon, Jong-soo Chang
    Abstract:

    New Colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 μM), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of Colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of Colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than Colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 nM, CT20126 induced 47% apoptosis among Jurkat T cells, whereas Colchicine induced only 33% apoptosis. Our results suggest that the Colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of Colchicine or Taxol.

  • The Colchicine Derivative CT20126 shows a novel microtubule-modulating activity with apoptosis
    Experimental & Molecular Medicine, 2013
    Co-Authors: Heon Seok, Taeg Kyu Kwon, Jong-soo Chang
    Abstract:

    Colchicine's value as an anticancer drug is undercut by harmful side effects, but a related compound may offer a useful alternative. Cell division is facilitated by dynamic assembly and disassembly of tubulin protein into microtubule filaments, which ensure that each new cell receives a full set of chromosomes. Colchicine thwarts cancerous growth by forcing microtubule disassembly. Since it can also be toxic to patients, Jong-Soo Chang of Korea's Daejin University and colleagues characterized the anticancer effects of a Colchicine Derivative called CT20126. Unlike Colchicine, CT20126 only transiently stimulates microtubule disassembly, and subsequently promotes aggregation of tubulin into unusually short, thick filaments. Nevertheless, CT20126 still proved a potent inhibitor of proliferation in cultured human cells, and triggered programmed cell death more efficiently than other microtubule-targeting drugs, highlighting its potential as a therapeutic candidate. New Colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 μ M ), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of Colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of Colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than Colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 n M , CT20126 induced 47% apoptosis among Jurkat T cells, whereas Colchicine induced only 33% apoptosis. Our results suggest that the Colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of Colchicine or Taxol.

Margareta Wallin - One of the best experts on this subject based on the ideXlab platform.

Soon-ok Kim - One of the best experts on this subject based on the ideXlab platform.

  • The Colchicine Derivative CT20126 shows a novel microtubule-modulating activity with apoptosis.
    Experimental & molecular medicine, 2013
    Co-Authors: Sung-kuk Kim, Heon Seok, Sang-min Cho, Ho Kim, Soon-ok Kim, Taeg Kyu Kwon, Jong-soo Chang
    Abstract:

    New Colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 μM), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of Colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of Colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than Colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 nM, CT20126 induced 47% apoptosis among Jurkat T cells, whereas Colchicine induced only 33% apoptosis. Our results suggest that the Colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of Colchicine or Taxol.

  • Colchicine-derived compound CT20126 promotes skin allograft survival by regulating the balance of Th1 and Th2 cytokine production
    Experimental & Molecular Medicine, 2007
    Co-Authors: Seon-jin Lee, Soon-ok Kim, Seung Namkoong, Woo-dong Nam, Young -uen Kwon, Hansoo Lee, Eun-young Yoon, Dong-jo Chang, Young-myeong Kim
    Abstract:

    Colchicine has been shown to regulate the expression of inflammatory gene, but this compound possesses much weaker anti-inflammatory activity. In this study, we synthesized a new Colchicine Derivative CT20126 and examined its immunomodulatory property. CT20126 was found to have immunosuppressive effects by inhibiting lymphocyte proliferation without cytotoxicity and effectively inhibit the transcriptional expression of the inflammatory genes, iNOS, TNF-α, and IL-1β, in macrophages stimulated by LPS. This effect was nearly comparable to that of cyclosporine A. This compound also significantly suppressed the production of nitric oxide and Th1-related pro-inflammatory cytokines, IL-1β, TNF-α, and IL-2, with minimal suppression of Th2-related anti-inflammatory cytokines IL-4 and IL-10 in the sponge matrix allograft model. Moreover, administration of CT20126 prolonged the survival of allograft skins from BALB/c mice (H-2d) to the dorsum of C57BL/6 (H-2b) mice. The in vivo immune suppressive effects of CT20126 were similar to that of cyclosporine A. These results indicate that this compound may have potential therapeutic value for transplantation rejection and other inflammatory diseases.

Sung-kuk Kim - One of the best experts on this subject based on the ideXlab platform.

  • The Colchicine Derivative CT20126 shows a novel microtubule-modulating activity with apoptosis.
    Experimental & molecular medicine, 2013
    Co-Authors: Sung-kuk Kim, Heon Seok, Sang-min Cho, Ho Kim, Soon-ok Kim, Taeg Kyu Kwon, Jong-soo Chang
    Abstract:

    New Colchicine analogs have been synthesized with the aim of developing stronger potential anticancer activities. Among the analogs, CT20126 has been previously reported to show immunosuppressive activities. Here, we report that CT20126 also shows potential anticancer effects via an unusual mechanism: the modulation of microtubule integrity and cell cycle arrest at the G2/M phase before apoptosis. When we treated COS-7 cells with CT20126 (5 μM), the normal thread-like microtubules were disrupted into tubulin dimers within 10 min and thereafter repolymerized into short, thick filaments. In contrast, cells treated with the same concentration of Colchicine exhibited microtubule depolymerization after 20 min and never underwent repolymerization. Furthermore, optical density (OD) analysis (350 nm) with purified tubulin showed that CT20126 had a higher repolymerizing activity than that of Taxol, a potent microtubule-polymerizing agent. These results suggest that the effects of CT20126 on microtubule integrity differ from those of Colchicine: the analog first destabilizes microtubules and then stabilizes the disrupted tubulins into short, thick polymers. Furthermore, CT20126 induced a greater level of apoptotic activity in Jurkat T cells than Colchicine (assessed by G2/M arrest, caspase-3 activation and cell sorting). At 20 nM, CT20126 induced 47% apoptosis among Jurkat T cells, whereas Colchicine induced only 33% apoptosis. Our results suggest that the Colchicine analog CT20126 can potently induce apoptosis by disrupting microtubule integrity in a manner that differs from that of Colchicine or Taxol.