Forskolin up-regulates metastasis-related phenotypes and molecules via protein kinase B, but not PI-3K, in H7721 human hepato-carcinoma cell line.
Forskolin (FSK) is known as an up-regulator of intracellular cAMP and inhibitor of cancer growth and metastasis. The effects of FSK on the metastasis potential and its mechanisms were studied using a human hepatocarcinoma cell line, H7721. It was found that FSK stimulated cell growth, increased cAMP in the cells, and enhanced the metastasis-related phenotypes, including adhesion to laminin (Ln) and human umbilical vein epithelial cells (HUVEC), chemotactic migration and invasion. These effects were supposed to result from the increase of the SLex expression induced by FSK, since only the monoclonal antibody of SLex showed a significant attenuation of the enhanced metastasis-associated phenotypes. Using H7721 cells transfected with the sense or antisense cDNA of protein kinase B (PKB) and some inhibitors of signal transduction, it was discovered that FSK up-regulated the expression of SLex via PKB, but it was independent of phosphotidylinositide-3-kinase (PI-3K). A subtype of atypical protein kinase C (a-PKC) might also participate in the up-regulation of SLex expression by FSK, and cAMP/PKA pathway is a negative regulator of SLex expression on H7721 cells. It can be concluded that FSK shows a metastasis-promoting effect ex vivo.
Wu
Shi-liang
SL
Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry, Shanghai Medical College of Fu-Dan University, Shanghai, China.
Ma
Jun
J
Qi
Hui-ling
HL
Zhang
Ying
Y
Zhang
Xia-ying
XY
Chen
Hui-li
HL
D000911:Antibodies, Monoclonal / Q000737:chemistry; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement; D002478:Cells, Cultured; D002633:Chemotaxis; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D007797:Laminin / Q000378:metabolism; D009362:Neoplasm Metastasis; D009844:Oligosaccharides / Q000378:metabolism; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D000080506:Sialyl Lewis X Antigen; D015398:Signal Transduction; D014162:Transfection; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D005576:Colforsin; D000242:Cyclic AMP; D018076:DNA, Complementary; D004791:Enzyme Inhibitors; D007797:Laminin; D009844:Oligosaccharides; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000080506:Sialyl Lewis X Antigen