Telomere-homologous G-rich oligonucleotides sensitize human ovarian cancer cells to TRAIL-induced growth inhibition and apoptosis.
Telomere-homologous G-rich oligonucleotides sensitize human ovarian cancer cells to TRAIL-induced growth inhibition and apoptosis.
复制标题
端粒同源富含 G 的寡核苷酸使人卵巢癌细胞对 TRAIL 诱导的生长抑制和细胞凋亡敏感。
DOI：
10.1089/nat.2012.0401
复制
发表时间：
2013
影响因子：
4
通讯作者：
Faller,DouglasV
中科院分区：
文献类型：
--
作者：
Sarkar,Sibaji;Faller,DouglasV
G-rich T-oligos (GT-oligos; oligonucleotides with homology to telomeres) elicit a DNA damage response in cells and induce cytotoxic effects in certain tumor cell lines. We have previously shown that GT-oligo inhibits growth, arrests cell cycle, and induces apoptosis in ovarian, pancreatic, and prostate cancer cells. However, not all ovarian cancer cell lines are susceptible to GT-oligo exposure. GT-oligo was found to induce transcript expression of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR-4 and DR-5, which are generally silenced in ovarian cancer cells, rendering them insensitive to TRAIL. Exposure of TRAIL- and GT-oligo-resistant cell lines to GT-oligo rendered them sensitive to the cytotoxic effects of TRAIL, producing more than additive inhibition of growth. An intracellular inhibitor of the extrinsic apoptotic pathway, FLICE-like Inhibitory Protein-Short (FLIPs), was down-regulated and Jun kinase (JNK) was activated by exposure to GT-oligo. JNK inhibition partially reversed the growth inhibition caused by the combination of GT-oligo and TRAIL indicating partial involvement of the Jun kinase pathway in the resulting cytotoxic effect. Both capase-8 and caspases 3/7 were activated by exposure to GT-oligo plus TRAIL, consistent with activation of the extrinsic apoptotic pathway. These results demonstrate a novel way of sensitizing resistant ovarian cancer cells to TRAIL-mediated cytotoxicity.
登录
查看更多内容
影响因子：
5.6
作者：
Rankin, Andrew M.;Sarkar, Sibaji;Faller, Douglas V.
通讯作者：
Faller, Douglas V.
影响因子：
32.4
作者：
Wiley, SR;Schooley, K;Goodwin, RG
通讯作者：
Goodwin, RG
影响因子：
4.6
作者：
Camidge, D. Ross
通讯作者：
Camidge, D. Ross
影响因子：
--
作者：
Sarkar, Sibaji;Faller, Douglas V.
通讯作者：
Faller, Douglas V.
人卵巢癌细胞的追踪活性：细胞毒性药物作用的增强。
影响因子：
8.4
作者：
S. Vignati;A. Codegoni;Federica Polato;Massimo Broggini;Maurizio D'Incalci
通讯作者：
Maurizio D'Incalci