Ginsenoside Rh2 induces ligand-independent Fas activation via lipid raft disruption.
Lipid rafts are plasma membrane platforms mediating signal transduction pathways for cellular proliferation, differentiation and apoptosis. Here, we show that membrane fluidity was increased in HeLa cells following treatment with ginsenoside Rh2 (Rh2), as determined by cell staining with carboxy-laurdan (C-laurdan), a two-photon dye designed for measuring membrane hydrophobicity. In the presence of Rh2, caveolin-1 appeared in non-raft fractions after sucrose gradient ultracentrifugation. In addition, caveolin-1 and GM1, lipid raft landmarkers, were internalized within cells after exposure to Rh2, indicating that Rh2 might disrupt lipid rafts. Since cholesterol overloading, which fortifies lipid rafts, prevented an increase in Rh2-induced membrane fluidity, caveolin-1 internalization and apoptosis, lipid rafts appear to be essential for Rh2-induced apoptosis. Moreover, Rh2-induced Fas oligomerization was abolished following cholesterol overloading, and Rh2-induced apoptosis was inhibited following treatment with siRNA for Fas. This result suggests that Rh2 is a novel lipid raft disruptor leading to Fas oligomerization and apoptosis.
Yi
Jae-Sung
JS
College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Choo
Hyo-Jung
HJ
Cho
Bong-Rae
BR
Kim
Hwan-Myung
HM
Kim
Yong-Nyun
YN
Ham
Young-Mi
YM
Ko
Young-Gyu
YG
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D051242:Caveolin 1 / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D000970:Antineoplastic Agents; D051242:Caveolin 1; D036145:Ginsenosides; D008024:Ligands; D019014:fas Receptor; C055305:ginsenoside Rh2; D002784:Cholesterol