A novel sesquiterpenoid dimer parviflorene F induces apoptosis by up-regulating the expression of TRAIL-R2 and a caspase-dependent mechanism.
Parviflorene F (1), a novel sesquiterpenoid dimer isolated from Curcuma parviflora Wall, is a cytotoxic compound. In this study, we examined the mechanism of its cytotoxic effect in HeLa cells. Treatment with 1 enhanced the mRNA and protein expression of TRAIL-R2 (tumor necrosis factor alpha-related apoptosis inducing ligand receptor 2). Apoptosis was induced by 1 as revealed by the distribution of DNA and Annexin V/PI staining using flow cytometry. In addition, 1-induced apoptosis was inhibited by human recombinant TRAIL-R2/Fc chimera protein, TRAIL-neutralizing fusion protein. Also, we found that 1 induced the activation of caspase-8, caspase-9, and caspase-3, indicating that the cytotoxic effect of 1 is correlated with apoptosis by a caspase-dependent mechanism through TRAIL-R2. In addition, 1 enhanced TRAIL-induced cell death against HeLa and TRAIL-resistant DLD1 cells. Taken together, up-regulation of TRAIL-R2 by 1 may contribute to sensitization of TRAIL-induced cell death.
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Takashi
T
Ohtsuki
Mayu
M
Tamaki
Kazuhumi
K
Toume
Masami
M
Ishibashi
D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001551:Benz(a)Anthracenes / Q000302:isolation & purification / Q000494:pharmacology*; D020169:Caspases; D045744:Cell Line, Tumor; D030024:Curcuma / Q000737:chemistry; D019281:Dimerization; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects* / Q000235:genetics; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D000970:Antineoplastic Agents; D001551:Benz(a)Anthracenes; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D012717:Sesquiterpenes; C529244:parviflorene F; D020169:Caspases