Upregulation of PTEN involved in scorpion venom-induced apoptosis in a lymphoma cell line.
We investigated whether the venom of the scorpion Buthus martensii Karsch (BmK) inhibited growth of human lymphoma cells by inducing apoptosis, and studied possible signal pathways involved in this cell death. BmK venom selectively reduced the viability of Raji and Jurkat cells, and had low toxicity to human peripheral blood lymphocytes. Flow cytometry showed that BmK venom-induced apoptosis and G(0)/G(1) cell cycle arrest in Raji and Jurkat cells. In Raji cells, BmK venom upregulated the expression of PTEN accompanied by decreased levels of Akt and Bad phosphorylation. Treatment with BmK venom and LY294002 (an inhibitor of Akt) synergistically enhanced apoptosis. The expression of p27 was increased in both PTEN-positive Raji and PTEN-negative Jurkat cells exposed to BmK venom. The results indicate that key regulators in BmK venom-induced apoptosis are PTEN, acting through downregulation of the PI3K/Akt signal pathway, in Raji cells and p27 in Jurkat cells.
Gao
Fang
F
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China.
Li
Hao
H
Chen
Ya-Dong
YD
Yu
Xiao-Ning
XN
Wang
Ran
R
Chen
Xue-Liang
XL
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D019169:Jurkat Cells; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009025:Morpholines / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012604:Scorpion Venoms / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*; D051025:bcl-Associated Death Protein / Q000378:metabolism
D002867:Chromones; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004791:Enzyme Inhibitors; D009025:Morpholines; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D012604:Scorpion Venoms; D051025:bcl-Associated Death Protein; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one