Search

Your search keyword '"Sureban SM"' showing total 3 results
Start Over Author "Sureban SM" Journal cancer research
3 results on '"Sureban SM"'

2. DCAMKL-1 regulates epithelial-mesenchymal transition in human pancreatic cells through a miR-200a-dependent mechanism.

Author

Sureban SM, May R, Lightfoot SA, Hoskins AB, Lerner M, Brackett DJ, Postier RG, Ramanujam R, Mohammed A, Rao CV, Wyche JH, Anant S, and Houchen CW

Subjects
14-3-3 Proteins metabolism, Animals, Biomarkers, Tumor metabolism, Cell Line, Tumor, Doublecortin-Like Kinases, Exonucleases metabolism, Exoribonucleases, Gene Expression, Homeodomain Proteins genetics, Humans, Immunohistochemistry, Intracellular Signaling Peptides and Proteins metabolism, Mice, Mice, Transgenic, Mutation, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Protein Serine-Threonine Kinases metabolism, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-myc metabolism, RNA Interference, Receptor, Notch1 genetics, Receptor, Notch1 metabolism, Repressor Proteins genetics, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors genetics, Twist-Related Protein 1 genetics, Vimentin metabolism, Zinc Finger E-box Binding Homeobox 2, Zinc Finger E-box-Binding Homeobox 1, ras Proteins genetics, ras Proteins metabolism, Epithelial-Mesenchymal Transition genetics, Intracellular Signaling Peptides and Proteins genetics, MicroRNAs genetics, Pancreatic Neoplasms genetics, Protein Serine-Threonine Kinases genetics
Abstract

Pancreatic cancer is an exceptionally aggressive disease in great need of more effective therapeutic options. Epithelial-mesenchymal transition (EMT) plays a key role in cancer invasion and metastasis, and there is a gain of stem cell properties during EMT. Here we report increased expression of the putative pancreatic stem cell marker DCAMKL-1 in an established KRAS transgenic mouse model of pancreatic cancer and in human pancreatic adenocarcinoma. Colocalization of DCAMKL-1 with vimentin, a marker of mesenchymal lineage, along with 14-3-3 σ was observed within premalignant PanIN lesions that arise in the mouse model. siRNA-mediated knockdown of DCAMKL-1 in human pancreatic cancer cells induced microRNA miR-200a, an EMT inhibitor, along with downregulation of EMT-associated transcription factors ZEB1, ZEB2, Snail, Slug, and Twist. Furthermore, DCAMKL-1 knockdown resulted in downregulation of c-Myc and KRAS through a let-7a microRNA-dependent mechanism, and downregulation of Notch-1 through a miR-144 microRNA-dependent mechanism. These findings illustrate direct regulatory links between DCAMKL-1, microRNAs, and EMT in pancreatic cancer. Moreover, they demonstrate a functional role for DCAMKL-1 in pancreatic cancer. Together, our results rationalize DCAMKL-1 as a therapeutic target for eradicating pancreatic cancers., (© 2011 AACR.)

Published
2011
Full Text
View/download PDF

3. Diphenyl difluoroketone: a curcumin derivative with potent in vivo anticancer activity.

Author

Subramaniam D, May R, Sureban SM, Lee KB, George R, Kuppusamy P, Ramanujam RP, Hideg K, Dieckgraefe BK, Houchen CW, and Anant S

Subjects
Adenocarcinoma genetics, Adenocarcinoma metabolism, Adenocarcinoma pathology, Animals, Apoptosis drug effects, Cell Cycle drug effects, Cell Growth Processes drug effects, Cell Line, Tumor, Colonic Neoplasms genetics, Colonic Neoplasms metabolism, Colonic Neoplasms pathology, Cyclooxygenase 2 biosynthesis, Cyclooxygenase 2 genetics, HCT116 Cells, HT29 Cells, Humans, Interleukin-8 biosynthesis, Interleukin-8 genetics, MAP Kinase Signaling System drug effects, Male, Mice, Mice, Nude, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic pathology, Stomach Neoplasms genetics, Stomach Neoplasms metabolism, Stomach Neoplasms pathology, Vascular Endothelial Growth Factor A biosynthesis, Vascular Endothelial Growth Factor A genetics, Xenograft Model Antitumor Assays, Adenocarcinoma drug therapy, Benzylidene Compounds pharmacology, Colonic Neoplasms drug therapy, Piperidones pharmacology, Stomach Neoplasms drug therapy
Abstract

Diphenyl difluoroketone (EF24), a molecule having structural similarity to curcumin, was reported to inhibit proliferation of a variety of cancer cells in vitro. However, the efficacy and in vivo mechanism of action of EF24 in gastrointestinal cancer cells have not been investigated. Here, we assessed the in vivo therapeutic effects of EF24 on colon cancer cells. Using hexosaminidase assay, we determined that EF24 inhibits proliferation of HCT-116 and HT-29 colon and AGS gastric adenocarcinoma cells but not of mouse embryo fibroblasts. Furthermore, the cancer cells showed increased levels of activated caspase-3 and increased Bax to Bcl-2 and Bax to Bcl-xL ratios, suggesting that the cells were undergoing apoptosis. At the same time, cell cycle analysis showed that there was an increased number of cells in the G(2)-M phase. To determine the effects of EF24 in vivo, HCT-116 colon cancer xenografts were established in nude mice and EF24 was given i.p. EF24 significantly suppressed the growth of colon cancer tumor xenografts. Immunostaining for CD31 showed that there was a lower number of microvessels in the EF24-treated animals coupled with decreased cyclooxygenase-2, interleukin-8, and vascular endothelial growth factor mRNA and protein expression. Western blot analyses also showed decreased AKT and extracellular signal-regulated kinase activation in the tumors. Taken together, these data suggest that the novel curcumin-related compound EF24 is a potent antitumor agent that induces caspase-mediated apoptosis during mitosis and has significant therapeutic potential for gastrointestinal cancers.

Published
2008
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results