The Experts below are selected from a list of 324 Experts worldwide ranked by ideXlab platform
Apparao Satyam - One of the best experts on this subject based on the ideXlab platform.
-
accidental discovery of a longer range vinylogous pummerer type lactonization formation of Sulindac sulfide lactone from Sulindac
Tetrahedron Letters, 2011Co-Authors: Somnath Halder, Apparao SatyamAbstract:Unexpected formation of Sulindac sulfide lactone occurred when Sulindac was treated with oxalyl chloride and triethylamine. Structurally analogous Sulindac sulfide and indomethacin did not undergo such lactonization under similar reaction conditions. We believe that the sulfoxide function in Sulindac plays a pivotal role possibly via a ‘longer-range’ vinylogous Pummerer-type reaction as a driving force for the observed lactonization. The structure of the lactone was confirmed by single crystal X-ray analysis.
-
Accidental discovery of a ‘longer-range’ vinylogous Pummerer-type lactonization: formation of Sulindac sulfide lactone from Sulindac
Tetrahedron Letters, 2011Co-Authors: Somnath Halder, Apparao SatyamAbstract:Unexpected formation of Sulindac sulfide lactone occurred when Sulindac was treated with oxalyl chloride and triethylamine. Structurally analogous Sulindac sulfide and indomethacin did not undergo such lactonization under similar reaction conditions. We believe that the sulfoxide function in Sulindac plays a pivotal role possibly via a ‘longer-range’ vinylogous Pummerer-type reaction as a driving force for the observed lactonization. The structure of the lactone was confirmed by single crystal X-ray analysis.
Somnath Halder - One of the best experts on this subject based on the ideXlab platform.
-
accidental discovery of a longer range vinylogous pummerer type lactonization formation of Sulindac sulfide lactone from Sulindac
Tetrahedron Letters, 2011Co-Authors: Somnath Halder, Apparao SatyamAbstract:Unexpected formation of Sulindac sulfide lactone occurred when Sulindac was treated with oxalyl chloride and triethylamine. Structurally analogous Sulindac sulfide and indomethacin did not undergo such lactonization under similar reaction conditions. We believe that the sulfoxide function in Sulindac plays a pivotal role possibly via a ‘longer-range’ vinylogous Pummerer-type reaction as a driving force for the observed lactonization. The structure of the lactone was confirmed by single crystal X-ray analysis.
-
Accidental discovery of a ‘longer-range’ vinylogous Pummerer-type lactonization: formation of Sulindac sulfide lactone from Sulindac
Tetrahedron Letters, 2011Co-Authors: Somnath Halder, Apparao SatyamAbstract:Unexpected formation of Sulindac sulfide lactone occurred when Sulindac was treated with oxalyl chloride and triethylamine. Structurally analogous Sulindac sulfide and indomethacin did not undergo such lactonization under similar reaction conditions. We believe that the sulfoxide function in Sulindac plays a pivotal role possibly via a ‘longer-range’ vinylogous Pummerer-type reaction as a driving force for the observed lactonization. The structure of the lactone was confirmed by single crystal X-ray analysis.
Frank A. Sinicrope - One of the best experts on this subject based on the ideXlab platform.
-
Sulindac sulfide–induced apoptosis is enhanced by a small-molecule Bcl-2 inhibitor and by TRAIL in human colon cancer cells overexpressing Bcl-2
Molecular cancer therapeutics, 2005Co-Authors: Frank A. Sinicrope, Robert C. PeningtonAbstract:Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) that induces apoptosis in cultured colon cancer cells and in intestinal epithelia in association with its chemopreventive efficacy. Resistance to Sulindac is well documented in patients with familial adenomatous polyposis; however, the molecular mechanisms underlying such resistance remain unknown. We determined the effect of ectopic Bcl-2 expression upon Sulindac-induced apoptotic signaling in SW480 human colon cancer cells. Sulindac sulfide activated both the caspase-8-dependent and mitochondrial apoptotic pathways. Ectopic Bcl-2 attenuated cytochrome c release and apoptosis induction compared with SW480/neo cells. Coadministration of Sulindac sulfide and the small-molecule Bcl-2 inhibitor HA14-1 increased apoptosis induction and enhanced caspase-8 and caspase-9 cleavage, Bax redistribution, and cytochrome c and second mitochondria-derived activator of caspase release. Given that Sulindac sulfide activated caspase-8 and increased membrane death receptor (DR4 and DR5) protein levels, we evaluated its combination with the endogenous death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Coadministration of Sulindac sulfide and TRAIL cooperatively enhanced apoptotic signaling as effectively as did HA14-1. Together, these data indicate that HA14-1 or TRAIL can enhance Sulindac sulfide-induced apoptosis and represent novel strategies for circumventing Bcl-2-mediated apoptosis resistance in human colon cancer cells.
-
Sulindac sulfide induced apoptosis is enhanced by a small molecule bcl 2 inhibitor and by trail in human colon cancer cells overexpressing bcl 2
Molecular Cancer Therapeutics, 2005Co-Authors: Frank A. Sinicrope, Robert C. PeningtonAbstract:Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) that induces apoptosis in cultured colon cancer cells and in intestinal epithelia in association with its chemopreventive efficacy. Resistance to Sulindac is well documented in patients with familial adenomatous polyposis; however, the molecular mechanisms underlying such resistance remain unknown. We determined the effect of ectopic Bcl-2 expression upon Sulindac-induced apoptotic signaling in SW480 human colon cancer cells. Sulindac sulfide activated both the caspase-8-dependent and mitochondrial apoptotic pathways. Ectopic Bcl-2 attenuated cytochrome c release and apoptosis induction compared with SW480/neo cells. Coadministration of Sulindac sulfide and the small-molecule Bcl-2 inhibitor HA14-1 increased apoptosis induction and enhanced caspase-8 and caspase-9 cleavage, Bax redistribution, and cytochrome c and second mitochondria-derived activator of caspase release. Given that Sulindac sulfide activated caspase-8 and increased membrane death receptor (DR4 and DR5) protein levels, we evaluated its combination with the endogenous death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Coadministration of Sulindac sulfide and TRAIL cooperatively enhanced apoptotic signaling as effectively as did HA14-1. Together, these data indicate that HA14-1 or TRAIL can enhance Sulindac sulfide-induced apoptosis and represent novel strategies for circumventing Bcl-2-mediated apoptosis resistance in human colon cancer cells.
-
Selective inhibitors of MEK1/ERK44/42 and p38 mitogen-activated protein kinases potentiate apoptosis induction by Sulindac sulfide in human colon carcinoma cells.
Molecular cancer therapeutics, 2005Co-Authors: Yunjie Sun, Frank A. SinicropeAbstract:The nonsteroidal anti-inflammatory drug (NSAID) Sulindac prevents experimental colon cancer and can regress precancerous polyps in humans. Sulindac sulfide inhibits cyclooxygenase (COX)-mediated prostaglandin synthesis and retards the growth of cultured colon cell lines primarily by inducing apoptosis. Given the known role of mitogen-activated protein kinase (MAPK) in signal transduction and the regulation of cell survival and death, we determined the effect of Sulindac sulfide on MAPK activation, COX-2 expression, and apoptosis induction in HCA-7 human colon cancer cells. Sulindac sulfide treatment was associated with activation of ERKp44/42 and p38 MAPK in a dosage- and time-dependent manner, and also activated upstream MEK. Similar results were seen in HCT-15 cells and also with the selective COX-2 inhibitor NS398. ERKp44/42 and p38 activation were accompanied by an induction of COX-2 protein expression. Selective inhibitors of Sulindac sulfide–induced ERKp44/42 (PD98059) and p38 MAPK (SB203580) activation also suppressed the induction of COX-2 by this NSAID. Furthermore, both MAPK inhibitors significantly augmented Sulindac sulfide–induced apoptosis, as did suppression of constitutive COX-2 using antisense oligonucleotides. In conclusion, MEK/ERK and p38 MAPK activation mediate COX-2 induction by Sulindac sulfide. Selective inhibitors of these MAPKs potentiate apoptosis induction by this NSAID, suggesting a novel strategy for the prevention or treatment of colorectal cancer.
-
selective inhibitors of mek1 erk44 42 and p38 mitogen activated protein kinases potentiate apoptosis induction by Sulindac sulfide in human colon carcinoma cells
Molecular Cancer Therapeutics, 2005Co-Authors: Yunjie Sun, Frank A. SinicropeAbstract:The nonsteroidal anti-inflammatory drug (NSAID) Sulindac prevents experimental colon cancer and can regress precancerous polyps in humans. Sulindac sulfide inhibits cyclooxygenase (COX)-mediated prostaglandin synthesis and retards the growth of cultured colon cell lines primarily by inducing apoptosis. Given the known role of mitogen-activated protein kinase (MAPK) in signal transduction and the regulation of cell survival and death, we determined the effect of Sulindac sulfide on MAPK activation, COX-2 expression, and apoptosis induction in HCA-7 human colon cancer cells. Sulindac sulfide treatment was associated with activation of ERKp44/42 and p38 MAPK in a dosage- and time-dependent manner, and also activated upstream MEK. Similar results were seen in HCT-15 cells and also with the selective COX-2 inhibitor NS398. ERKp44/42 and p38 activation were accompanied by an induction of COX-2 protein expression. Selective inhibitors of Sulindac sulfide–induced ERKp44/42 (PD98059) and p38 MAPK (SB203580) activation also suppressed the induction of COX-2 by this NSAID. Furthermore, both MAPK inhibitors significantly augmented Sulindac sulfide–induced apoptosis, as did suppression of constitutive COX-2 using antisense oligonucleotides. In conclusion, MEK/ERK and p38 MAPK activation mediate COX-2 induction by Sulindac sulfide. Selective inhibitors of these MAPKs potentiate apoptosis induction by this NSAID, suggesting a novel strategy for the prevention or treatment of colorectal cancer.
Robert C. Penington - One of the best experts on this subject based on the ideXlab platform.
-
Sulindac sulfide–induced apoptosis is enhanced by a small-molecule Bcl-2 inhibitor and by TRAIL in human colon cancer cells overexpressing Bcl-2
Molecular cancer therapeutics, 2005Co-Authors: Frank A. Sinicrope, Robert C. PeningtonAbstract:Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) that induces apoptosis in cultured colon cancer cells and in intestinal epithelia in association with its chemopreventive efficacy. Resistance to Sulindac is well documented in patients with familial adenomatous polyposis; however, the molecular mechanisms underlying such resistance remain unknown. We determined the effect of ectopic Bcl-2 expression upon Sulindac-induced apoptotic signaling in SW480 human colon cancer cells. Sulindac sulfide activated both the caspase-8-dependent and mitochondrial apoptotic pathways. Ectopic Bcl-2 attenuated cytochrome c release and apoptosis induction compared with SW480/neo cells. Coadministration of Sulindac sulfide and the small-molecule Bcl-2 inhibitor HA14-1 increased apoptosis induction and enhanced caspase-8 and caspase-9 cleavage, Bax redistribution, and cytochrome c and second mitochondria-derived activator of caspase release. Given that Sulindac sulfide activated caspase-8 and increased membrane death receptor (DR4 and DR5) protein levels, we evaluated its combination with the endogenous death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Coadministration of Sulindac sulfide and TRAIL cooperatively enhanced apoptotic signaling as effectively as did HA14-1. Together, these data indicate that HA14-1 or TRAIL can enhance Sulindac sulfide-induced apoptosis and represent novel strategies for circumventing Bcl-2-mediated apoptosis resistance in human colon cancer cells.
-
Sulindac sulfide induced apoptosis is enhanced by a small molecule bcl 2 inhibitor and by trail in human colon cancer cells overexpressing bcl 2
Molecular Cancer Therapeutics, 2005Co-Authors: Frank A. Sinicrope, Robert C. PeningtonAbstract:Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) that induces apoptosis in cultured colon cancer cells and in intestinal epithelia in association with its chemopreventive efficacy. Resistance to Sulindac is well documented in patients with familial adenomatous polyposis; however, the molecular mechanisms underlying such resistance remain unknown. We determined the effect of ectopic Bcl-2 expression upon Sulindac-induced apoptotic signaling in SW480 human colon cancer cells. Sulindac sulfide activated both the caspase-8-dependent and mitochondrial apoptotic pathways. Ectopic Bcl-2 attenuated cytochrome c release and apoptosis induction compared with SW480/neo cells. Coadministration of Sulindac sulfide and the small-molecule Bcl-2 inhibitor HA14-1 increased apoptosis induction and enhanced caspase-8 and caspase-9 cleavage, Bax redistribution, and cytochrome c and second mitochondria-derived activator of caspase release. Given that Sulindac sulfide activated caspase-8 and increased membrane death receptor (DR4 and DR5) protein levels, we evaluated its combination with the endogenous death receptor ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Coadministration of Sulindac sulfide and TRAIL cooperatively enhanced apoptotic signaling as effectively as did HA14-1. Together, these data indicate that HA14-1 or TRAIL can enhance Sulindac sulfide-induced apoptosis and represent novel strategies for circumventing Bcl-2-mediated apoptosis resistance in human colon cancer cells.
Saeed M Sheikh - One of the best experts on this subject based on the ideXlab platform.
-
DOI: 10.4255/mcpharmacol.09.11 Molecular and Cellular Pharmacology www.mcpharmacol.com Sulindac Sulfide Differentially Induces Apoptosis in Smac- Proficient and-Deficient Human Colon Cancer Cells
2015Co-Authors: Jingxue Shi, Hong Sun, Ying Huang, Saeed M SheikhAbstract:Sulindac, the non-steroidal anti-inflammatory drug has shown promise in the prevention of colon cancer but the molecular mechanisms by which it mediates such effects remain to be elucidated. Sulindac sulfide is the major active metabolite of Sulindac and believed to be responsible for mediating the effects of Sulindac. Previously, our group and others have shown that Sulindac sulfide induces apoptosis by engaging death receptor and mitochondrial pathways and that a cross-talk exists between these two pathways during Sulindac sulfide-induced apoptosis. Second mitochondrial-derived activator (Smac) is an important pro-apoptotic molecule that activate
-
Sulindac sulfide induced apoptosis involves death receptor 5 and the caspase 8 dependent pathway in human colon and prostate cancer cells
Cancer Research, 2001Co-Authors: Ying Huang, Michael J Hillman, Rong Rong, Saeed M SheikhAbstract:Sulindac is the most extensively investigated clinically relevant chemopreventive nonsteroidal anti-inflammatory drug. Sulindac sulfide is one of the major metabolites of Sulindac that is believed to mediate its antitumorigenic effects by inducing apoptosis. Recent evidence suggests that Sulindac sulfide engages the mitochondrial pathway involving caspase 9 and Bax to mediate its apoptotic effects [Zhang et al. , Science (Wash. DC), 290: 989–992, 2000]. In this report, we demonstrate that Sulindac sulfide also engaged the membrane death receptor (DR) pathway to mediate apoptosis. Sulindac sulfide up-regulated DR5 and activated the proximal caspase 8 in various different colon and prostate cancer cell lines. Sulindac sulfide specifically up-regulated the DR5 levels but had no effect on the levels of other DRs including DR4, Fas, and tumor necrosis factor receptor 1. To further delineate the role of DR5 in Sulindac sulfide-induced apoptosis, we used JCA-1 prostate cancer cells that are deficient in mounting a Fas and tumor necrosis factor receptor 1-dependent apoptotic response but are proficient in mediating DR5-dependent apoptosis. JCA-1 cells were stably transfected with dominant-negative Fas-associated death domain to block the flow of apoptotic signals originating from the endogenous DR5, and Sulindac sulfide-induced apoptosis was investigated. Our results indicated that by blocking the DR5-dependent apoptotic pathway, dominant-negative Fas-associated death domain did indeed inhibit Sulindac sulfide-induced apoptosis. Furthermore, exogenous tumor necrosis factor-related apoptosis-inducing ligand, the ligand for DR5, also potentiated Sulindac sulfide-induced apoptosis in all of the cell lines tested, thereby further supporting the involvement of DR5 in Sulindac sulfide-induced apoptosis. Thus, our results demonstrate that Sulindac sulfide also engages the membrane DR pathway involving DR5 and proximal caspase 8 to induce apoptosis.
