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4 results on '"Terence K. Lee"'

1. FTY720 induces apoptosis of human hepatoma cell lines through PI3-K-mediated Akt dephosphorylation

Author

Ray Xu, Joanna W. Ho, Xianghong Wang, Yong-Chuan Wong, Terence K. Lee, Kevin Tak-Pan Ng, Irene Oi-Lin Ng, Chris K. Sun, Sheung Tat Fan, and Kwan Man

Subjects
Cancer Research, Programmed cell death, Carcinoma, Hepatocellular, Down-Regulation, Apoptosis, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Biology, Dephosphorylation, Glycogen Synthase Kinase 3, Phosphatidylinositol 3-Kinases, Cyclin D1, Sphingosine, Proto-Oncogene Proteins, hemic and lymphatic diseases, Tumor Cells, Cultured, Humans, Enzyme Inhibitors, Phosphorylation, Protein kinase B, PI3K/AKT/mTOR pathway, Mitogen-Activated Protein Kinase 1, Glycogen Synthase Kinase 3 beta, Mitogen-Activated Protein Kinase 3, Fingolimod Hydrochloride, Kinase, Tumor Suppressor Proteins, Liver cell, Liver Neoplasms, G1 Phase, General Medicine, Cell cycle, Cell biology, Propylene Glycols, Tumor Suppressor Protein p53, Proto-Oncogene Proteins c-akt, Cyclin-Dependent Kinase Inhibitor p27, Immunosuppressive Agents
Abstract

Our aim was to study the anticancer effect of the novel immunomodulator FTY720 in vitro and in vivo by investigation of cell cycle entry, cell cycle regulation, cell survival and apoptosis pathways. Three hepatoma cell lines with different p53 statuses (HepG2, Huh-7 and Hep3B) and one non-tumorigenic immortalized liver cell line (MIHA) were used for an in vitro study. The in vivo effects of FTY720 were evaluated in a nude mouse tumor model. Cell cycle distribution and cell cycle regulator proteins p27(Kip1) and cyclin D1, together with the PI3-K/Akt pathway, mitogen-activated protein kinases and cleaved caspase-3 and caspase-9, were evaluated. FTY720 selectively induced cell apoptosis in hepatoma cell lines with overexpression of cleaved caspase-3 and caspase-9, but the same phenomena were not found in MIHA cells. FTY720 induced Akt dephosphorylation at Ser473 mediated by phosphoinositide 3-kinase (PI3-K) inhibition. Dephosphorylation led to down-regulation of p42/p44 and dephosphorylation of Forkhead transcription factor and GSK-3beta and, subsequently, up-regulation of p27(Kip1) and down-regulation of cyclin D1. In our in vivo model FTY720 induced apoptosis of tumor cells by down-regulation of the Akt pathway. FTY720 suppressed tumor growth without notable side-effects in normal liver. In conclusion, FTY720 is a novel anticancer agent that induces apoptosis of hepatoma cell lines both in vitro and in vivo through PI3-K-mediated Akt dephosphorylation in a p53-independent manner.

Published
2004

2. Significance of the Rac signaling pathway in HCC cell motility: implications for a new therapeutic target

Author

Kwan Man, Xianghong Wang, Sheung Tat Fan, Ray Xu, Irene Oi-Lin Ng, Chris K. Sun, Joanna W. Ho, Ronnie T.P. Poon, Kevin Tak-Pan Ng, and Terence K. Lee

Subjects
Cancer Research, Pathology, medicine.medical_specialty, Carcinoma, Hepatocellular, MAP Kinase Signaling System, Motility, Metastasis, Phosphatidylinositol 3-Kinases, Cell Movement, Sphingosine, Cell Line, Tumor, medicine, Humans, Neoplasm Metastasis, Cytoskeleton, neoplasms, Phosphoinositide-3 Kinase Inhibitors, business.industry, Fingolimod Hydrochloride, Liver Neoplasms, General Medicine, medicine.disease, Primary tumor, Fingolimod, digestive system diseases, rac GTP-Binding Proteins, Cell culture, Propylene Glycols, Hepatocellular carcinoma, Cancer research, Signal transduction, business, medicine.drug, Signal Transduction
Abstract

Recurrence and metastasis are commonly associated with poor prognosis of hepatocellular carcinoma (HCC). Therefore, a better understanding of molecular mechanisms involved in HCC metastasis may lead to more effective treatment for HCC patients. Rac plays important roles in cytoskeletal reorganization leading to cell motility in renal and breast carcinomas. However, the role of Rac is controversial in tumors and has not been studied in HCC. The aim of this study was to investigate the importance of the Rac signaling pathway in HCC cell motility and the anti-metastatic potential of FTY720. Recently a pair of HCC cell lines from a primary tumor (H2P) and its matched metastasis (H2M) was established. These two cell lines provide a useful tool for the study of HCC metastasis. The results show that the Rac signaling pathway is activated in the metastatic HCC cell line (H2M) compared with the primary HCC cell line (H2P). FTY720 specifically suppressed H2M cell motility by down-regulation of the Rac-GTP level through inhibition of phosphoinositide 3-kinase activity. To conclude, this study is the first to demonstrate an essential role of Rac signaling pathway activation in HCC metastasis and suppression of cell motility by FTY720 through blocking of the Rac pathway.

Published
2004

3. Significance of the Rac signaling pathway in HCC cell motility: implications for a new therapeutic target.

Author

Terence K. Lee, Kwan Man, Joanna W. Ho, Xiang Hong Wang, Ronnie T. Poon, Chris K. Sun, Kevin T. Ng, Irene O. Ng, Ray Xu, and Sheung Tat Fan

Subjects
PATHOLOGY, CANCER patients, BREAST cancer, CANCER
Abstract

Recurrence and metastasis are commonly associated with poor prognosis of hepatocellular carcinoma (HCC). Therefore, a better understanding of molecular mechanisms involved in HCC metastasis may lead to more effective treatment for HCC patients. Rac plays important roles in cytoskeletal reorganization leading to cell motility in renal and breast carcinomas. However, the role of Rac is controversial in tumors and has not been studied in HCC. The aim of this study was to investigate the importance of the Rac signaling pathway in HCC cell motility and the anti-metastatic potential of FTY720. Recently a pair of HCC cell lines from a primary tumor (H2P) and its matched metastasis (H2M) was established. These two cell lines provide a useful tool for the study of HCC metastasis. The results show that the Rac signaling pathway is activated in the metastatic HCC cell line (H2M) compared with the primary HCC cell line (H2P). FTY720 specifically suppressed H2M cell motility by down-regulation of the RacGTP level through inhibition of phosphoinositide 3-kinase activity. To conclude, this study is the first to demonstrate an essential role of Rac signaling pathway activation in HCC metastasis and suppression of cell motility by FTY720 through blocking of the Rac pathway. [ABSTRACT FROM AUTHOR]

Published
2005
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4. FTY720 induces apoptosis of human hepatoma cell lines through PI3-K-mediated Akt dephosphorylation.

Author

Terence K. Lee, Kwan Man, Joanna W. Ho, Chris K. Sun, Kevin T. Ng, Xiang Hong Wang, Yong Chuan Wong, Irene O. Ng, Ray Xu, and Sheung Tat Fan

Subjects
REGULATION of cell growth, APOPTOSIS, CELL death, HEPATOCELLULAR carcinoma
Abstract

Our aim was to study the anticancer effect of the novel immunomodulator FTY720 in vitro and in vivo by investigation of cell cycle entry, cell cycle regulation, cell survival and apoptosis pathways. Three hepatoma cell lines with different p53 statuses (HepG2, Huh-7 and Hep3B) and one non-tumorigenic immortalized liver cell line (MIHA) were used for an in vitro study. The in vivo effects of FTY720 were evaluated in a nude mouse tumor model. Cell cycle distribution and cell cycle regulator proteins p27Kip1 and cyclin D1, together with the PI3-K/Akt pathway, mitogen-activated protein kinases and cleaved caspase-3 and caspase-9, were evaluated. FTY720 selectively induced cell apoptosis in hepatoma cell lines with overexpression of cleaved caspase-3 and caspase-9, but the same phenomena were not found in MIHA cells. FTY720 induced Akt dephosphorylation at Ser473 mediated by phosphoinositide 3-kinase (PI3-K) inhibition. Dephosphorylation led to down-regulation of p42/p44 and dephosphorylation of Forkhead transcription factor and GSK-3 and, subsequently, up-regulation of p27Kip1 and down-regulation of cyclin D1. In our in vivo model FTY720 induced apoptosis of tumor cells by down-regulation of the Akt pathway. FTY720 suppressed tumor growth without notable side-effects in normal liver. In conclusion, FTY720 is a novel anticancer agent that induces apoptosis of hepatoma cell lines both in vitro and in vivo through PI3-K-mediated Akt dephosphorylation in a p53-independent manner. [ABSTRACT FROM AUTHOR]

Published
2004
Full Text
View/download PDF

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