Gerhard Sperl
University of the Pacific (United States)
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Gerhard Sperl.
Biochemical Pharmacology | 2002
Han Li; Li Liu; Mary David; Clark M. Whitehead; Ming Chen; John Fetter; Gerhard Sperl; Rifat Pamukcu; W. Joseph Thompson
Exisulind and its analogues are inhibitors of cyclic GMP phosphodiesterases (PDEs) that have been shown to activate and induce protein kinase G, resulting in the induction of apoptosis in colon cancer cells. These drugs also reduce beta-catenin protein levels and decrease cyclin D1 mRNA levels in SW480 cells. Herein we report on studies pertaining to exisulind regulation of beta-catenin levels and activity in colon tumor cells. Exisulind and its higher-affinity PDE analogues, (Z)-5-fluoro-2-methyl-(4-pyridylidene)-3-(N-benzyl)-indenylacetamide hydrochloride (CP461) and (Z)-1H-indene-3-acetamide, 5-fluoro-2-methyl-N-(phenylmethyl)-1-[(3,4,5-trimethoxyphenyl)methylene] (CP248), reduced beta-catenin, including the nuclear beta-catenin in SW480 cells (EC(50) approximately 200 microM, 1 microM, and <1 microM, respectively). The 50% reduction of beta-catenin was seen in 8-14 hr. There was no change in beta-catenin mRNA. Exisulind-induced beta-catenin reduction was blocked by the proteasomal inhibitor MG132 (Z-leu-Leu-Leu-CHO), indicating that the effect of exisulind involved ubiquitin-proteasomal degradation. A consequence of reduced beta-catenin in SW480 cells was that exisulind, CP461, and CP248 caused a concentration- and time-dependent decrease in cyclin D1 levels (EC(50) approximately 300 microM, 1 microM, and <1 microM, respectively) in 4 hr. The effect was via decreased cyclin D1 mRNA levels. Exisulind-induced degradation of beta-catenin was not blocked by the inhibition of caspase-3 activity and/or apoptosis, and some SW480 cells showed a reduction in beta-catenin levels before the appearance of early apoptosis indicators. Expression of the N-terminal 170 amino acid fragment of beta-catenin reduced the effects of beta-catenin degradation, cyclin D1 reduction, and the apoptosis response to exisulind. These results indicate that exisulind-induced beta-catenin degradation precedes the induction of apoptosis and that the down-regulation of inappropriate beta-catenin-activated genes accounts in part for the pro-apoptotic effects of exisulind and CP461 in colon tumor cells.
Journal of Labelled Compounds and Radiopharmaceuticals | 1999
Gerhard Sperl; Rifat Pamukcu; Klaus Brendel; Paul H. Gross
A new method of radioactive labeling via sulfonium salts and 14C alkylhalides is reported, along with a novel synthesis of (E)-rac-(2′-buten-1′,4′-olido)-[3′,4′:1,2]-6-fluoro-2-methyl-3-(4-[14C-methyl]-sulfonylbenzylidene)-indan (scheme 1, compound 14CH3-SO2-L]), a drug that showed very high activity, when tested in various tumor cell lines (1). Copyright
Cancer Research | 1995
Gary A. Piazza; Alanna L. Kulchak Rahm; Mary Krutzsch; Gerhard Sperl; Nancy Shipp Paranka; Paul H. Gross; Klaus Brendel; Randall W. Burt; David S. Alberts; Rifat Pamukcu; Dennis J. Ahnen
Cancer Research | 1997
Gary A. Piazza; David S. Alberts; Lee J. Hixson; Nancy Shipp Paranka; Han Li; Tyler S. Finn; Cheryl L. Bogert; Jose Guillen; Klaus Brendel; Paul H. Gross; Gerhard Sperl; Justine M. Ritchie; Randall W. Burt; Lansing G. Ellsworth; Dennis J. Ahnen; Rifat Pamukcu
Cancer Research | 2000
W. Thompson; Gary A. Piazza; Han Li; Li Liu; John Fetter; Bing Zhu; Gerhard Sperl; Dennis J. Ahnen; Rifat Pamukcu
Biochemical Pharmacology | 1999
Jin T. E. Lim; Gary A. Piazza; Edward K. Han; Thomas M. Delohery; Han Li; Tyler S. Finn; Ralph Buttyan; Hirofumi Yamamoto; Gerhard Sperl; Klaus Brendel; Paul H. Gross; Rifat Pamukcu; I. Bernard Weinstein
Journal of Pharmacology and Experimental Therapeutics | 2001
Li Liu; Han Li; Tashandra Underwood; Marti Lloyd; Mary David; Gerhard Sperl; Rifat Pamukcu; W. Joseph Thompson
Archive | 1998
Gerhard Sperl; Rifat Pamukcu; Ulrich Ixkes; Gary A. Piazza
Archive | 1997
Gerhard Sperl; Paul H. Gross; Klaus Brendel; Rifat Pamukcu; Gary A. Piazza
Archive | 1998
Xiaojing Wang; Gerhard Sperl; Paul H. Gross; Rifat Pamukcu; Gary A. Piazza