The Experts below are selected from a list of 81 Experts worldwide ranked by ideXlab platform
Donald Kufe - One of the best experts on this subject based on the ideXlab platform.
-
a novel Isocoumarin Derivative induces mitotic phase arrest and apoptosis of human multiple myeloma cells
2006Co-Authors: Takeshi Kawano, Naoki Agata, Surender Kharbanda, David Avigan, Donald KufeAbstract:The Isocoumarin NM-3 reverses resistance of human multiple myeloma (MM) cells to dexamethasone and is in clinical trials. In the present work, the NM-3 analog, 185322, has been studied for activity against MM cells. Human U266, RPMI8226 and primary MM cells were analyzed for the effects of 185322 on cell cycle distribution, tubulin polymerization and induction of apoptosis. We show that, in contrast to NM-3, treatment with 185322 is associated with a marked arrest of MM cells in M phase. The results also demonstrate that treatment with 185322 is associated with a rapid decrease in tubulin assembly and an increase in Bcl-2 phosphorylation, consistent with disruption of mitosis. Our results further demonstrate that mitotic failure induced by 185322 results in activation of an apoptotic response in MM cell lines and primary MM cells. By contrast, 185322 had little if any effect on growth and survival of human carcinoma cells. These findings identify a novel inhibitor of microtubule assembly that induces mitotic arrest and apoptosis of MM cells.
-
2 8 hydroxy 6 methoxy 1 oxo 1h 2 benzopyran 3 yl propionic acid a small molecule Isocoumarin potentiates dexamethasone induced apoptosis of human multiple myeloma cells
2004Co-Authors: Naoki Agata, Hiroko Nogi, Michael Milhollen, Surender Kharbanda, Donald KufeAbstract:2-(8-Hydroxy-6-methoxy-1-oxo-1Eta-2-benzopyran-3-yl)propionic acid (NM-3) is a small molecule Isocoumarin Derivative that has recently entered clinical trials as an orally bioavailable anticancer agent. NM-3 induces lethality of human carcinoma cells by both apoptotic and nonapoptotic mechanisms and potentiates the effects of cytotoxic chemotherapeutic agents. The present studies have evaluated the effects of NM-3 on human multiple myeloma (MM) cells. The results demonstrate that NM-3 potentiates dexamethasone-induced killing of both dexamethasone-sensitive MM1.S and dexamethasone-resistant RPMI8226 and U266 MM cells. We show that NM-3 enhances dexamethasone-induced release of the mitochondrial apoptogenic factors cytochrome c and Smac/DIABLO. The results also demonstrate that NM-3 enhances dexamethasone-induced activation of the intrinsic caspase-9->caspase-3 apoptotic pathway. In concert with these results, NM-3 potentiates dexamethasone-induced apoptosis of MM1.S cells. Moreover, NM-3 acts synergistically with dexamethasone in inducing apoptosis of the dexamethasone-resistant RPMI8226 and U266 MM cells. These findings indicate that NM-3 may be effective in combination with dexamethasone in the treatment of MM.
-
the novel Isocoumarin 2 8 hydroxy 6 methoxy 1 oxo 1h 2 benzopyran 3 yl propionic acid nm 3 induces lethality of human carcinoma cells by generation of reactive oxygen species1
2001Co-Authors: Li Yin, Surender Kharbanda, Tsuneya Ohno, Ralph R Weichselbaum, Donald KufeAbstract:Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3) is an Isocoumarin Derivative that has recently entered clinical trials for evaluation as a p.o.-bioavailable, antiangiogenic molecule. NM-3 induces endothelial cell death at low M concentrations by a nonapoptotic mechanism. The present studies have assessed the direct effects of NM-3 on human carcinoma cells. The results demonstrate that NM-3 treatment is associated with the generation of reactive oxygen species and loss of clonogenic survival. In concert with these findings, we show that exposure to NM-3 is associated with increases in expression of the p53 tumor suppressor. In human MCF-7 and ZR-75-1 breast cancer cells, NM- 3 induces the p21 cyclin-dependent kinase inhibitor, cell cycle arrest at G 1-S-phase, and necrotic cell death. Moreover, human PA-1 ovarian carcinoma and HeLa cervical carcinoma cells respond to NM-3 with the induction of apoptosis by a reactive oxygen species- dependent mechanism. These findings demonstrate that NM-3 has direct effects on carcinoma cells at clinically achievable concentrations and that this agent could be effective in targeting both the tumor and its vasculature.
Surender Kharbanda - One of the best experts on this subject based on the ideXlab platform.
-
a novel Isocoumarin Derivative induces mitotic phase arrest and apoptosis of human multiple myeloma cells
2006Co-Authors: Takeshi Kawano, Naoki Agata, Surender Kharbanda, David Avigan, Donald KufeAbstract:The Isocoumarin NM-3 reverses resistance of human multiple myeloma (MM) cells to dexamethasone and is in clinical trials. In the present work, the NM-3 analog, 185322, has been studied for activity against MM cells. Human U266, RPMI8226 and primary MM cells were analyzed for the effects of 185322 on cell cycle distribution, tubulin polymerization and induction of apoptosis. We show that, in contrast to NM-3, treatment with 185322 is associated with a marked arrest of MM cells in M phase. The results also demonstrate that treatment with 185322 is associated with a rapid decrease in tubulin assembly and an increase in Bcl-2 phosphorylation, consistent with disruption of mitosis. Our results further demonstrate that mitotic failure induced by 185322 results in activation of an apoptotic response in MM cell lines and primary MM cells. By contrast, 185322 had little if any effect on growth and survival of human carcinoma cells. These findings identify a novel inhibitor of microtubule assembly that induces mitotic arrest and apoptosis of MM cells.
-
2 8 hydroxy 6 methoxy 1 oxo 1h 2 benzopyran 3 yl propionic acid a small molecule Isocoumarin potentiates dexamethasone induced apoptosis of human multiple myeloma cells
2004Co-Authors: Naoki Agata, Hiroko Nogi, Michael Milhollen, Surender Kharbanda, Donald KufeAbstract:2-(8-Hydroxy-6-methoxy-1-oxo-1Eta-2-benzopyran-3-yl)propionic acid (NM-3) is a small molecule Isocoumarin Derivative that has recently entered clinical trials as an orally bioavailable anticancer agent. NM-3 induces lethality of human carcinoma cells by both apoptotic and nonapoptotic mechanisms and potentiates the effects of cytotoxic chemotherapeutic agents. The present studies have evaluated the effects of NM-3 on human multiple myeloma (MM) cells. The results demonstrate that NM-3 potentiates dexamethasone-induced killing of both dexamethasone-sensitive MM1.S and dexamethasone-resistant RPMI8226 and U266 MM cells. We show that NM-3 enhances dexamethasone-induced release of the mitochondrial apoptogenic factors cytochrome c and Smac/DIABLO. The results also demonstrate that NM-3 enhances dexamethasone-induced activation of the intrinsic caspase-9->caspase-3 apoptotic pathway. In concert with these results, NM-3 potentiates dexamethasone-induced apoptosis of MM1.S cells. Moreover, NM-3 acts synergistically with dexamethasone in inducing apoptosis of the dexamethasone-resistant RPMI8226 and U266 MM cells. These findings indicate that NM-3 may be effective in combination with dexamethasone in the treatment of MM.
-
the novel Isocoumarin 2 8 hydroxy 6 methoxy 1 oxo 1h 2 benzopyran 3 yl propionic acid nm 3 induces lethality of human carcinoma cells by generation of reactive oxygen species1
2001Co-Authors: Li Yin, Surender Kharbanda, Tsuneya Ohno, Ralph R Weichselbaum, Donald KufeAbstract:Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3) is an Isocoumarin Derivative that has recently entered clinical trials for evaluation as a p.o.-bioavailable, antiangiogenic molecule. NM-3 induces endothelial cell death at low M concentrations by a nonapoptotic mechanism. The present studies have assessed the direct effects of NM-3 on human carcinoma cells. The results demonstrate that NM-3 treatment is associated with the generation of reactive oxygen species and loss of clonogenic survival. In concert with these findings, we show that exposure to NM-3 is associated with increases in expression of the p53 tumor suppressor. In human MCF-7 and ZR-75-1 breast cancer cells, NM- 3 induces the p21 cyclin-dependent kinase inhibitor, cell cycle arrest at G 1-S-phase, and necrotic cell death. Moreover, human PA-1 ovarian carcinoma and HeLa cervical carcinoma cells respond to NM-3 with the induction of apoptosis by a reactive oxygen species- dependent mechanism. These findings demonstrate that NM-3 has direct effects on carcinoma cells at clinically achievable concentrations and that this agent could be effective in targeting both the tumor and its vasculature.
Naoki Agata - One of the best experts on this subject based on the ideXlab platform.
-
a novel Isocoumarin Derivative induces mitotic phase arrest and apoptosis of human multiple myeloma cells
2006Co-Authors: Takeshi Kawano, Naoki Agata, Surender Kharbanda, David Avigan, Donald KufeAbstract:The Isocoumarin NM-3 reverses resistance of human multiple myeloma (MM) cells to dexamethasone and is in clinical trials. In the present work, the NM-3 analog, 185322, has been studied for activity against MM cells. Human U266, RPMI8226 and primary MM cells were analyzed for the effects of 185322 on cell cycle distribution, tubulin polymerization and induction of apoptosis. We show that, in contrast to NM-3, treatment with 185322 is associated with a marked arrest of MM cells in M phase. The results also demonstrate that treatment with 185322 is associated with a rapid decrease in tubulin assembly and an increase in Bcl-2 phosphorylation, consistent with disruption of mitosis. Our results further demonstrate that mitotic failure induced by 185322 results in activation of an apoptotic response in MM cell lines and primary MM cells. By contrast, 185322 had little if any effect on growth and survival of human carcinoma cells. These findings identify a novel inhibitor of microtubule assembly that induces mitotic arrest and apoptosis of MM cells.
-
2 8 hydroxy 6 methoxy 1 oxo 1h 2 benzopyran 3 yl propionic acid a small molecule Isocoumarin potentiates dexamethasone induced apoptosis of human multiple myeloma cells
2004Co-Authors: Naoki Agata, Hiroko Nogi, Michael Milhollen, Surender Kharbanda, Donald KufeAbstract:2-(8-Hydroxy-6-methoxy-1-oxo-1Eta-2-benzopyran-3-yl)propionic acid (NM-3) is a small molecule Isocoumarin Derivative that has recently entered clinical trials as an orally bioavailable anticancer agent. NM-3 induces lethality of human carcinoma cells by both apoptotic and nonapoptotic mechanisms and potentiates the effects of cytotoxic chemotherapeutic agents. The present studies have evaluated the effects of NM-3 on human multiple myeloma (MM) cells. The results demonstrate that NM-3 potentiates dexamethasone-induced killing of both dexamethasone-sensitive MM1.S and dexamethasone-resistant RPMI8226 and U266 MM cells. We show that NM-3 enhances dexamethasone-induced release of the mitochondrial apoptogenic factors cytochrome c and Smac/DIABLO. The results also demonstrate that NM-3 enhances dexamethasone-induced activation of the intrinsic caspase-9->caspase-3 apoptotic pathway. In concert with these results, NM-3 potentiates dexamethasone-induced apoptosis of MM1.S cells. Moreover, NM-3 acts synergistically with dexamethasone in inducing apoptosis of the dexamethasone-resistant RPMI8226 and U266 MM cells. These findings indicate that NM-3 may be effective in combination with dexamethasone in the treatment of MM.
Li Yin - One of the best experts on this subject based on the ideXlab platform.
-
the novel Isocoumarin 2 8 hydroxy 6 methoxy 1 oxo 1h 2 benzopyran 3 yl propionic acid nm 3 induces lethality of human carcinoma cells by generation of reactive oxygen species1
2001Co-Authors: Li Yin, Surender Kharbanda, Tsuneya Ohno, Ralph R Weichselbaum, Donald KufeAbstract:Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3) is an Isocoumarin Derivative that has recently entered clinical trials for evaluation as a p.o.-bioavailable, antiangiogenic molecule. NM-3 induces endothelial cell death at low M concentrations by a nonapoptotic mechanism. The present studies have assessed the direct effects of NM-3 on human carcinoma cells. The results demonstrate that NM-3 treatment is associated with the generation of reactive oxygen species and loss of clonogenic survival. In concert with these findings, we show that exposure to NM-3 is associated with increases in expression of the p53 tumor suppressor. In human MCF-7 and ZR-75-1 breast cancer cells, NM- 3 induces the p21 cyclin-dependent kinase inhibitor, cell cycle arrest at G 1-S-phase, and necrotic cell death. Moreover, human PA-1 ovarian carcinoma and HeLa cervical carcinoma cells respond to NM-3 with the induction of apoptosis by a reactive oxygen species- dependent mechanism. These findings demonstrate that NM-3 has direct effects on carcinoma cells at clinically achievable concentrations and that this agent could be effective in targeting both the tumor and its vasculature.
Tsuneya Ohno - One of the best experts on this subject based on the ideXlab platform.
-
the novel Isocoumarin 2 8 hydroxy 6 methoxy 1 oxo 1h 2 benzopyran 3 yl propionic acid nm 3 induces lethality of human carcinoma cells by generation of reactive oxygen species1
2001Co-Authors: Li Yin, Surender Kharbanda, Tsuneya Ohno, Ralph R Weichselbaum, Donald KufeAbstract:Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3) is an Isocoumarin Derivative that has recently entered clinical trials for evaluation as a p.o.-bioavailable, antiangiogenic molecule. NM-3 induces endothelial cell death at low M concentrations by a nonapoptotic mechanism. The present studies have assessed the direct effects of NM-3 on human carcinoma cells. The results demonstrate that NM-3 treatment is associated with the generation of reactive oxygen species and loss of clonogenic survival. In concert with these findings, we show that exposure to NM-3 is associated with increases in expression of the p53 tumor suppressor. In human MCF-7 and ZR-75-1 breast cancer cells, NM- 3 induces the p21 cyclin-dependent kinase inhibitor, cell cycle arrest at G 1-S-phase, and necrotic cell death. Moreover, human PA-1 ovarian carcinoma and HeLa cervical carcinoma cells respond to NM-3 with the induction of apoptosis by a reactive oxygen species- dependent mechanism. These findings demonstrate that NM-3 has direct effects on carcinoma cells at clinically achievable concentrations and that this agent could be effective in targeting both the tumor and its vasculature.
