The Experts below are selected from a list of 123 Experts worldwide ranked by ideXlab platform

Jongsup Park - One of the best experts on this subject based on the ideXlab platform.

  • novel retinoic acid Derivative abpn has potent inhibitory activity on cell growth and apoptosis in cancer cells
    International Journal of Cancer, 2003
    Co-Authors: Soojong Um, Younja Kwon, Siho Park, Jongsup Park
    Abstract:

    Retinoids are natural and synthetic Derivatives of vitamin A that have great promise for cancer therapy and chemoprevention. Of the Retinoids developed so far, 4-(N-hydroxyphenyl)retinamide (4-HPR or fenretinide) appears to have the best therapeutic potential in vitro and in vivo and is currently being tested in clinical trials for cancer prevention and therapy. To develop other potentially potent antitumor agents, we synthesized 85 Retinoid Derivatives. In an initial screening of these synthetic Retinoids using the HCT116 colon cancer cell line, we found that 4-amino-2-(butyrylamino)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate (ABPN or CBG41) induced the greatest growth inhibition, with an IC50 value of 0.6 μM. Subsequent studies in other cancer cell lines indicated that ABPN was much more growth-inhibitory than all-trans retinoic acid or 4-HPR. Compared to 4-HPR, ABPN induced 5.5- to 70.0-fold more growth inhibition in most cancer cells, with the exception of gynecologic cancer cells. In these cells, the antiproliferative effect was only 1.5- to 2.8-fold more than 4-HPR. We examined the molecular mechanism underlying the difference in growth inhibition between 4-HPR and ABPN. DAPI staining, DNA fragmentation, FACS and Western blotting analyses suggest that ABPN induced apoptosis by activating caspase-3 and -8, which may result in increased PARP cleavage. Unlike 4-HPR, ABPN activated all 3 RAR isotypes to an extent similar to AtRA. In addition, ABPN significantly inhibited AP-1 transcriptional activity and thus greatly suppressed the expression of the matrix metalloproteinase -1, -2 and -3 genes, which are involved in tumor invasion. These results suggest that ABPN may be a promising Retinoid Derivative offering not only enhanced cytotoxicity, but also increased inhibition of tumor invasiveness. © 2003 Wiley-Liss, Inc.

  • Novel retinoic acid Derivative ABPN has potent inhibitory activity on cell growth and apoptosis in cancer cells.
    International journal of cancer, 2003
    Co-Authors: Hye-sook Han, Younja Kwon, Siho Park, Young-soy Rho, Hong-sig Sin, Jongsup Park
    Abstract:

    Retinoids are natural and synthetic Derivatives of vitamin A that have great promise for cancer therapy and chemoprevention. Of the Retinoids developed so far, 4-(N-hydroxyphenyl)retinamide (4-HPR or fenretinide) appears to have the best therapeutic potential in vitro and in vivo and is currently being tested in clinical trials for cancer prevention and therapy. To develop other potentially potent antitumor agents, we synthesized 85 Retinoid Derivatives. In an initial screening of these synthetic Retinoids using the HCT116 colon cancer cell line, we found that 4-amino-2-(butyrylamino)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate (ABPN or CBG41) induced the greatest growth inhibition, with an IC(50) value of 0.6 microM. Subsequent studies in other cancer cell lines indicated that ABPN was much more growth-inhibitory than all-trans retinoic acid or 4-HPR. Compared to 4-HPR, ABPN induced 5.5- to 70.0-fold more growth inhibition in most cancer cells, with the exception of gynecologic cancer cells. In these cells, the antiproliferative effect was only 1.5- to 2.8-fold more than 4-HPR. We examined the molecular mechanism underlying the difference in growth inhibition between 4-HPR and ABPN. DAPI staining, DNA fragmentation, FACS and Western blotting analyses suggest that ABPN induced apoptosis by activating caspase-3 and -8, which may result in increased PARP cleavage. Unlike 4-HPR, ABPN activated all 3 RAR isotypes to an extent similar to AtRA. In addition, ABPN significantly inhibited AP-1 transcriptional activity and thus greatly suppressed the expression of the matrix metalloproteinase -1, -2 and -3 genes, which are involved in tumor invasion. These results suggest that ABPN may be a promising Retinoid Derivative offering not only enhanced cytotoxicity, but also increased inhibition of tumor invasiveness.

Dongdong Chen - One of the best experts on this subject based on the ideXlab platform.

  • SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target.
    Nature communications, 2019
    Co-Authors: Shuofeng Yuan, Hin Chu, Jasper Fuk-woo Chan, Lei Wen, Bingpeng Yan, Pok-man Lai, Kah-meng Tee, Jingjing Huang, Dongdong Chen
    Abstract:

    Viruses are obligate intracellular microbes that exploit the host metabolic machineries to meet their biosynthetic demands, making these host pathways potential therapeutic targets. Here, by exploring a lipid library, we show that AM580, a Retinoid Derivative and RAR-α agonist, is highly potent in interrupting the life cycle of diverse viruses including Middle East respiratory syndrome coronavirus and influenza A virus. Using click chemistry, the overexpressed sterol regulatory element binding protein (SREBP) is shown to interact with AM580, which accounts for its broad-spectrum antiviral activity. Mechanistic studies pinpoint multiple SREBP proteolytic processes and SREBP-regulated lipid biosynthesis pathways, including the downstream viral protein palmitoylation and double-membrane vesicles formation, that are indispensable for virus replication. Collectively, our study identifies a basic lipogenic transactivation event with broad relevance to human viral infections and represents SREBP as a potential target for the development of broad-spectrum antiviral strategies.

  • SREBP-dependent lipidomic reprogramming as a broad-spectrum antiviral target
    Nature Publishing Group, 2019
    Co-Authors: Shuofeng Yuan, Hin Chu, Jasper Fuk-woo Chan, Lei Wen, Bingpeng Yan, Pok-man Lai, Kah-meng Tee, Jingjing Huang, Dongdong Chen
    Abstract:

    Viruses rely on host cell metabolism for replication, making these pathways potential therapeutic targets. Here, the authors show that AM580, a Retinoid Derivative and RAR-α agonist, affects replication of several RNA viruses by interfering with the activity of SREBP

Siho Park - One of the best experts on this subject based on the ideXlab platform.

  • In vitro antitumor potential of 4-BPRE, a butyryl aminophenyl ester of retinoic acid: Role of the butyryl group
    Oncology reports, 2004
    Co-Authors: Hye-sook Han, Younja Kwon, Siho Park, Tae-sung Bae, Young-soy Rho, Hong-sig Sin
    Abstract:

    Retinoic acid (RA) and sodium butyrate (NaB) have been implicated in the regulation of growth and differentiation in various cancer cells. To produce an agent with the properties of both RA and NaB, a butyryl aminophenyl ester of RA (4-BPRE) was synthesized. The agent was compared with an aminophenyl ester devoid of the butyryl group (4-APRE) for antitumor potential in vitro. Like RA, 4-hydroxyphenyl retinamide (4-HPR) and 4-APRE, 4-BPRE was an active ligand for all three subtypes of RAR, but not for RXR, as determined by transcription assays in COS-1 cells. In addition, regardless of the butyryl group, 4-BPRE actively suppressed c-Jun transcriptional activity, which may result in reduced expression of matrix metalloproteinases (MMP-1 and MMP-2), and effectively inhibited HCT116 cell invasion into Matrigel. In these respects, 4-BPRE is similar to 4-APRE, and even to RA and 4-HPR. However, our results showed that in HCT116 colon and A549 lung cancer cells, 4-BPRE was much more cytotoxic than RA and 4-APRE, and was also more cytotoxic than 4-HPR, which is the most cytotoxic Retinoid Derivative under clinical investigation. Subsequent assays using DAPI staining, DNA fragmentation, and FACS analysis suggested that the cytotoxic effect of 4-BPRE is mediated by apoptosis in HCT116 cells. Moreover, 4-BPRE inhibited histone deacetylase (HDAC) activity to some degree, although inhibition was less than that induced by the known HDAC inhibitors TSA and NaB. These results suggest that 4-BPRE could be a promising antitumor Retinoid with both NaB activity and RA function.

  • novel retinoic acid Derivative abpn has potent inhibitory activity on cell growth and apoptosis in cancer cells
    International Journal of Cancer, 2003
    Co-Authors: Soojong Um, Younja Kwon, Siho Park, Jongsup Park
    Abstract:

    Retinoids are natural and synthetic Derivatives of vitamin A that have great promise for cancer therapy and chemoprevention. Of the Retinoids developed so far, 4-(N-hydroxyphenyl)retinamide (4-HPR or fenretinide) appears to have the best therapeutic potential in vitro and in vivo and is currently being tested in clinical trials for cancer prevention and therapy. To develop other potentially potent antitumor agents, we synthesized 85 Retinoid Derivatives. In an initial screening of these synthetic Retinoids using the HCT116 colon cancer cell line, we found that 4-amino-2-(butyrylamino)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate (ABPN or CBG41) induced the greatest growth inhibition, with an IC50 value of 0.6 μM. Subsequent studies in other cancer cell lines indicated that ABPN was much more growth-inhibitory than all-trans retinoic acid or 4-HPR. Compared to 4-HPR, ABPN induced 5.5- to 70.0-fold more growth inhibition in most cancer cells, with the exception of gynecologic cancer cells. In these cells, the antiproliferative effect was only 1.5- to 2.8-fold more than 4-HPR. We examined the molecular mechanism underlying the difference in growth inhibition between 4-HPR and ABPN. DAPI staining, DNA fragmentation, FACS and Western blotting analyses suggest that ABPN induced apoptosis by activating caspase-3 and -8, which may result in increased PARP cleavage. Unlike 4-HPR, ABPN activated all 3 RAR isotypes to an extent similar to AtRA. In addition, ABPN significantly inhibited AP-1 transcriptional activity and thus greatly suppressed the expression of the matrix metalloproteinase -1, -2 and -3 genes, which are involved in tumor invasion. These results suggest that ABPN may be a promising Retinoid Derivative offering not only enhanced cytotoxicity, but also increased inhibition of tumor invasiveness. © 2003 Wiley-Liss, Inc.

  • Novel retinoic acid Derivative ABPN has potent inhibitory activity on cell growth and apoptosis in cancer cells.
    International journal of cancer, 2003
    Co-Authors: Hye-sook Han, Younja Kwon, Siho Park, Young-soy Rho, Hong-sig Sin, Jongsup Park
    Abstract:

    Retinoids are natural and synthetic Derivatives of vitamin A that have great promise for cancer therapy and chemoprevention. Of the Retinoids developed so far, 4-(N-hydroxyphenyl)retinamide (4-HPR or fenretinide) appears to have the best therapeutic potential in vitro and in vivo and is currently being tested in clinical trials for cancer prevention and therapy. To develop other potentially potent antitumor agents, we synthesized 85 Retinoid Derivatives. In an initial screening of these synthetic Retinoids using the HCT116 colon cancer cell line, we found that 4-amino-2-(butyrylamino)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate (ABPN or CBG41) induced the greatest growth inhibition, with an IC(50) value of 0.6 microM. Subsequent studies in other cancer cell lines indicated that ABPN was much more growth-inhibitory than all-trans retinoic acid or 4-HPR. Compared to 4-HPR, ABPN induced 5.5- to 70.0-fold more growth inhibition in most cancer cells, with the exception of gynecologic cancer cells. In these cells, the antiproliferative effect was only 1.5- to 2.8-fold more than 4-HPR. We examined the molecular mechanism underlying the difference in growth inhibition between 4-HPR and ABPN. DAPI staining, DNA fragmentation, FACS and Western blotting analyses suggest that ABPN induced apoptosis by activating caspase-3 and -8, which may result in increased PARP cleavage. Unlike 4-HPR, ABPN activated all 3 RAR isotypes to an extent similar to AtRA. In addition, ABPN significantly inhibited AP-1 transcriptional activity and thus greatly suppressed the expression of the matrix metalloproteinase -1, -2 and -3 genes, which are involved in tumor invasion. These results suggest that ABPN may be a promising Retinoid Derivative offering not only enhanced cytotoxicity, but also increased inhibition of tumor invasiveness.

Younja Kwon - One of the best experts on this subject based on the ideXlab platform.

  • In vitro antitumor potential of 4-BPRE, a butyryl aminophenyl ester of retinoic acid: Role of the butyryl group
    Oncology reports, 2004
    Co-Authors: Hye-sook Han, Younja Kwon, Siho Park, Tae-sung Bae, Young-soy Rho, Hong-sig Sin
    Abstract:

    Retinoic acid (RA) and sodium butyrate (NaB) have been implicated in the regulation of growth and differentiation in various cancer cells. To produce an agent with the properties of both RA and NaB, a butyryl aminophenyl ester of RA (4-BPRE) was synthesized. The agent was compared with an aminophenyl ester devoid of the butyryl group (4-APRE) for antitumor potential in vitro. Like RA, 4-hydroxyphenyl retinamide (4-HPR) and 4-APRE, 4-BPRE was an active ligand for all three subtypes of RAR, but not for RXR, as determined by transcription assays in COS-1 cells. In addition, regardless of the butyryl group, 4-BPRE actively suppressed c-Jun transcriptional activity, which may result in reduced expression of matrix metalloproteinases (MMP-1 and MMP-2), and effectively inhibited HCT116 cell invasion into Matrigel. In these respects, 4-BPRE is similar to 4-APRE, and even to RA and 4-HPR. However, our results showed that in HCT116 colon and A549 lung cancer cells, 4-BPRE was much more cytotoxic than RA and 4-APRE, and was also more cytotoxic than 4-HPR, which is the most cytotoxic Retinoid Derivative under clinical investigation. Subsequent assays using DAPI staining, DNA fragmentation, and FACS analysis suggested that the cytotoxic effect of 4-BPRE is mediated by apoptosis in HCT116 cells. Moreover, 4-BPRE inhibited histone deacetylase (HDAC) activity to some degree, although inhibition was less than that induced by the known HDAC inhibitors TSA and NaB. These results suggest that 4-BPRE could be a promising antitumor Retinoid with both NaB activity and RA function.

  • novel retinoic acid Derivative abpn has potent inhibitory activity on cell growth and apoptosis in cancer cells
    International Journal of Cancer, 2003
    Co-Authors: Soojong Um, Younja Kwon, Siho Park, Jongsup Park
    Abstract:

    Retinoids are natural and synthetic Derivatives of vitamin A that have great promise for cancer therapy and chemoprevention. Of the Retinoids developed so far, 4-(N-hydroxyphenyl)retinamide (4-HPR or fenretinide) appears to have the best therapeutic potential in vitro and in vivo and is currently being tested in clinical trials for cancer prevention and therapy. To develop other potentially potent antitumor agents, we synthesized 85 Retinoid Derivatives. In an initial screening of these synthetic Retinoids using the HCT116 colon cancer cell line, we found that 4-amino-2-(butyrylamino)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate (ABPN or CBG41) induced the greatest growth inhibition, with an IC50 value of 0.6 μM. Subsequent studies in other cancer cell lines indicated that ABPN was much more growth-inhibitory than all-trans retinoic acid or 4-HPR. Compared to 4-HPR, ABPN induced 5.5- to 70.0-fold more growth inhibition in most cancer cells, with the exception of gynecologic cancer cells. In these cells, the antiproliferative effect was only 1.5- to 2.8-fold more than 4-HPR. We examined the molecular mechanism underlying the difference in growth inhibition between 4-HPR and ABPN. DAPI staining, DNA fragmentation, FACS and Western blotting analyses suggest that ABPN induced apoptosis by activating caspase-3 and -8, which may result in increased PARP cleavage. Unlike 4-HPR, ABPN activated all 3 RAR isotypes to an extent similar to AtRA. In addition, ABPN significantly inhibited AP-1 transcriptional activity and thus greatly suppressed the expression of the matrix metalloproteinase -1, -2 and -3 genes, which are involved in tumor invasion. These results suggest that ABPN may be a promising Retinoid Derivative offering not only enhanced cytotoxicity, but also increased inhibition of tumor invasiveness. © 2003 Wiley-Liss, Inc.

  • Novel retinoic acid Derivative ABPN has potent inhibitory activity on cell growth and apoptosis in cancer cells.
    International journal of cancer, 2003
    Co-Authors: Hye-sook Han, Younja Kwon, Siho Park, Young-soy Rho, Hong-sig Sin, Jongsup Park
    Abstract:

    Retinoids are natural and synthetic Derivatives of vitamin A that have great promise for cancer therapy and chemoprevention. Of the Retinoids developed so far, 4-(N-hydroxyphenyl)retinamide (4-HPR or fenretinide) appears to have the best therapeutic potential in vitro and in vivo and is currently being tested in clinical trials for cancer prevention and therapy. To develop other potentially potent antitumor agents, we synthesized 85 Retinoid Derivatives. In an initial screening of these synthetic Retinoids using the HCT116 colon cancer cell line, we found that 4-amino-2-(butyrylamino)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate (ABPN or CBG41) induced the greatest growth inhibition, with an IC(50) value of 0.6 microM. Subsequent studies in other cancer cell lines indicated that ABPN was much more growth-inhibitory than all-trans retinoic acid or 4-HPR. Compared to 4-HPR, ABPN induced 5.5- to 70.0-fold more growth inhibition in most cancer cells, with the exception of gynecologic cancer cells. In these cells, the antiproliferative effect was only 1.5- to 2.8-fold more than 4-HPR. We examined the molecular mechanism underlying the difference in growth inhibition between 4-HPR and ABPN. DAPI staining, DNA fragmentation, FACS and Western blotting analyses suggest that ABPN induced apoptosis by activating caspase-3 and -8, which may result in increased PARP cleavage. Unlike 4-HPR, ABPN activated all 3 RAR isotypes to an extent similar to AtRA. In addition, ABPN significantly inhibited AP-1 transcriptional activity and thus greatly suppressed the expression of the matrix metalloproteinase -1, -2 and -3 genes, which are involved in tumor invasion. These results suggest that ABPN may be a promising Retinoid Derivative offering not only enhanced cytotoxicity, but also increased inhibition of tumor invasiveness.

Hye-sook Han - One of the best experts on this subject based on the ideXlab platform.

  • In vitro antitumor potential of 4-BPRE, a butyryl aminophenyl ester of retinoic acid: Role of the butyryl group
    Oncology reports, 2004
    Co-Authors: Hye-sook Han, Younja Kwon, Siho Park, Tae-sung Bae, Young-soy Rho, Hong-sig Sin
    Abstract:

    Retinoic acid (RA) and sodium butyrate (NaB) have been implicated in the regulation of growth and differentiation in various cancer cells. To produce an agent with the properties of both RA and NaB, a butyryl aminophenyl ester of RA (4-BPRE) was synthesized. The agent was compared with an aminophenyl ester devoid of the butyryl group (4-APRE) for antitumor potential in vitro. Like RA, 4-hydroxyphenyl retinamide (4-HPR) and 4-APRE, 4-BPRE was an active ligand for all three subtypes of RAR, but not for RXR, as determined by transcription assays in COS-1 cells. In addition, regardless of the butyryl group, 4-BPRE actively suppressed c-Jun transcriptional activity, which may result in reduced expression of matrix metalloproteinases (MMP-1 and MMP-2), and effectively inhibited HCT116 cell invasion into Matrigel. In these respects, 4-BPRE is similar to 4-APRE, and even to RA and 4-HPR. However, our results showed that in HCT116 colon and A549 lung cancer cells, 4-BPRE was much more cytotoxic than RA and 4-APRE, and was also more cytotoxic than 4-HPR, which is the most cytotoxic Retinoid Derivative under clinical investigation. Subsequent assays using DAPI staining, DNA fragmentation, and FACS analysis suggested that the cytotoxic effect of 4-BPRE is mediated by apoptosis in HCT116 cells. Moreover, 4-BPRE inhibited histone deacetylase (HDAC) activity to some degree, although inhibition was less than that induced by the known HDAC inhibitors TSA and NaB. These results suggest that 4-BPRE could be a promising antitumor Retinoid with both NaB activity and RA function.

  • Novel retinoic acid Derivative ABPN has potent inhibitory activity on cell growth and apoptosis in cancer cells.
    International journal of cancer, 2003
    Co-Authors: Hye-sook Han, Younja Kwon, Siho Park, Young-soy Rho, Hong-sig Sin, Jongsup Park
    Abstract:

    Retinoids are natural and synthetic Derivatives of vitamin A that have great promise for cancer therapy and chemoprevention. Of the Retinoids developed so far, 4-(N-hydroxyphenyl)retinamide (4-HPR or fenretinide) appears to have the best therapeutic potential in vitro and in vivo and is currently being tested in clinical trials for cancer prevention and therapy. To develop other potentially potent antitumor agents, we synthesized 85 Retinoid Derivatives. In an initial screening of these synthetic Retinoids using the HCT116 colon cancer cell line, we found that 4-amino-2-(butyrylamino)phenyl(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexenyl)-2,4,6,8-nonatetraenoate (ABPN or CBG41) induced the greatest growth inhibition, with an IC(50) value of 0.6 microM. Subsequent studies in other cancer cell lines indicated that ABPN was much more growth-inhibitory than all-trans retinoic acid or 4-HPR. Compared to 4-HPR, ABPN induced 5.5- to 70.0-fold more growth inhibition in most cancer cells, with the exception of gynecologic cancer cells. In these cells, the antiproliferative effect was only 1.5- to 2.8-fold more than 4-HPR. We examined the molecular mechanism underlying the difference in growth inhibition between 4-HPR and ABPN. DAPI staining, DNA fragmentation, FACS and Western blotting analyses suggest that ABPN induced apoptosis by activating caspase-3 and -8, which may result in increased PARP cleavage. Unlike 4-HPR, ABPN activated all 3 RAR isotypes to an extent similar to AtRA. In addition, ABPN significantly inhibited AP-1 transcriptional activity and thus greatly suppressed the expression of the matrix metalloproteinase -1, -2 and -3 genes, which are involved in tumor invasion. These results suggest that ABPN may be a promising Retinoid Derivative offering not only enhanced cytotoxicity, but also increased inhibition of tumor invasiveness.