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3-Oxoolean-12-en-27-oic acid isolated from Aceriphyllum rossii induces caspase-8-dependent apoptosis in human promyelocytic leukemia HL-60 cells.
Kim, Sung-Su; Won, So-Jung; Kim, Nam Jae; Yoo, Jae Kuk; Bae, KiHwan; Lee, Kyung-Tae.
Afiliação
  • Kim SS; College of Pharmacy, Kyung-Hee University, Seoul, Republic of Korea.
Biol Pharm Bull ; 32(1): 91-8, 2009 Jan.
Article em En | MEDLINE | ID: mdl-19122287
In the present study, we investigated the effects of 3-oxoolean-12-en-27-oic acid (3-OA) isolated from the underground parts of Aceriphyllum rossii (Saxifragaceae) on the viability and apoptosis of HL-60 human promyelocytic leukemia cells, and the mechanisms underlying its action. 3-OA-treated HL-60 cells and HeLa human cervix adenocarcinoma cells displayed several apoptotic features, such as, DNA fragmentation, DNA laddering by agarose gel electrophoresis, and hypodiploid DNA contents by flow cytometry, and 3-OA also caused the activations of caspase-8, -9 and -3. Pretreatment with z-VAD-fmk (a broad-caspase inhibitor) almost completely suppressed 3-OA-induced DNA ladder formation and hypodiploid DNA contents, thereby implicating the caspase cascade in the apoptotic process. In addition, z-IETD-fmk (a caspase-8 inhibitor) and z-DEVD-fmk (a caspase-3 inhibitor) also completely neutralized the apoptotic effect of 3-OA in HL-60 cells. Furthermore, 3-OA increased Fas-related protein contents and the mRNA expressions of Fas ligand (FasL), Fas, and Fas-associated death domain (FADD). Preincubation with anti-Fas or anti-FasL blocking antibodies completely prevented 3-OA-induced apoptosis. Taken together, these results suggest that 3-oxoolean-12-en-27-oic acid induces apoptosis by activating caspase-8 via FasL-stimulated death receptor signaling.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triterpenos / Apoptose / Células HL-60 / Saxifragaceae / Caspase 8 Limite: Humans Idioma: En Revista: Biol Pharm Bull Assunto da revista: BIOQUIMICA / FARMACOLOGIA Ano de publicação: 2009 Tipo de documento: Article
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Triterpenos / Apoptose / Células HL-60 / Saxifragaceae / Caspase 8 Limite: Humans Idioma: En Revista: Biol Pharm Bull Assunto da revista: BIOQUIMICA / FARMACOLOGIA Ano de publicação: 2009 Tipo de documento: Article