TY - JOUR
T1 - A novel sesquiterpenoid dimer parviflorene F induces apoptosis by up-regulating the expression of TRAIL-R2 and a caspase-dependent mechanism
AU - Ohtsuki, Takashi
AU - Tamaki, Mayu
AU - Toume, Kazuhumi
AU - Ishibashi, Masami
N1 - Funding Information:
We thank Professor Kazuki Saito and Dr. Masaaki Noji (Chiba University) for the use of the real time PCR instrument, Dr. Hiroaki Kodama (Chiba University) for the use of the flow cytometer, Dr. Bingliang Fang, The University of Texas, MD, Anderson Cancer Center for generous gift of TRAIL-resistant DLD1 cells, and Dr. Masaaki Sato for helpful discussions at the beginning of this study. This work was partly supported by a Grant-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, from the Kampou Science Foundation, and from the Shorai Foundation for Science and Technology.
PY - 2008/2/15
Y1 - 2008/2/15
N2 - 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 1enhanced the mRNA and protein expression of TRAIL-R2 (tumor necrosis factor α-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.
AB - 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 1enhanced the mRNA and protein expression of TRAIL-R2 (tumor necrosis factor α-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.
KW - Apoptosis
KW - Caspase
KW - Sesquiterpenoid dimer
KW - TRAIL-R2
UR - http://www.scopus.com/inward/record.url?scp=38949133427&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2007.11.022
DO - 10.1016/j.bmc.2007.11.022
M3 - 学術論文
C2 - 18036820
AN - SCOPUS:38949133427
SN - 0968-0896
VL - 16
SP - 1756
EP - 1763
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 4
ER -