Tanshinone IIA induces TRAIL sensitization of human lung cancer cells through selective ER stress induction.
نویسندگان
چکیده
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promised anticancer medicine targeting only the tumor, most cancers show resistance to TRAIL-induced apoptosis. For this reason, new therapeutic strategies to overcome the TRAIL resistance are required for more effective tumor treatment. In the present study, potential of tanshinone IIA as a TRAIL sensitizer was evaluated in human non-small cell lung cancer (NSCLC) cells. NSCLC cells showed resistance to TRAIL-mediated cell death, but combination treatment of Tanshinone IIA and TRAIL synergistically decreased cell viability and increased apoptosis in TRAIL-resistant NSCLC cells. Tanshinone IIA greatly induced death receptor 5 (DR5), but not death receptor 4 (DR4). Furthermore, DR5 knockdown attenuated the combination treatment of tanshinone IIA with TRAIL-mediated cell death in human NSCLC cells. Tanshinone IIA also increased CHOP and activated the PERK-ATF4 pathway suggesting that tanshinone IIA increased DR5 and CHOP by activating the PERK-ATF4 pathway. Tanshinone IIA also downregulated phosphorylation of STAT3 and expression of survivin. Taken together, these results indicate that tanshinone IIA increases TRAIL-induced cell death via upregulating DR5 and downregulating survivin mediated by, respectively, selective activation of PERK/ATF4 and inhibition of STAT3, suggesting combinatorial intervention of tanshinone IIA and TRAIL as a new therapeutic strategy for human NSCLC.
منابع مشابه
Tanshinone IIA Could Inhibit Pancreatic Cancer BxPC-3 Cells through Increasing PERK, ATF6, Caspase-12 and CHOP Expression to Induce Apoptosis
Tanshinone IIA (Tan-IIA) is extracted from Dan-Shen. Tan-IIA could inhibit human pancreatic cancer BxPC-3 cells through decreasing TCTP, Mcl-1 and Bcl-xl expression in vitro. Our previous study showed that Tan-IIA can inhibit hepatocellular carcinoma hep-J5 cells and human breast cancer BT-20 cells through inducing endoplasmic reticulum (ER) stress. In the present study, we investigated the ER ...
متن کاملTanshinone IIA induces apoptosis in human lung cancer A549 cells through the induction of reactive oxygen species and decreasing the mitochondrial membrane potential.
Tanshinone IIA (Tan-IIA) is extracted from Danshen and known to inhibit proliferation and induce apoptosis in many cancer cells. We aimed to elucidate its anticancer activity and molecular mechanism in human lung cancer A549 cells. The cytotoxicity of Tan-IIA in A549 cells were measured by the MTT assay. The effects of Tan-IIA on the cell cycle, mitochondrial membrane potential (MMP), calcium a...
متن کاملExperimental study of the anti-cancer mechanism of tanshinone IIA against human breast cancer.
Tanshinone IIA is a widely used Chinese herbal medicine isolated from Danshen (Salvia miltiorrhiza). Recent studies indicate that tanshinone IIA may have anti-inflammatory and anti-oxidant properties, as well as cytotoxic activities against multiple human cancer cell lines. This study was performed to determine the anti-cancer activity of tanshinone IIA on human breast cancer cells in vitro and...
متن کاملTanshinone IIA may inhibit the growth of small cell lung cancer H146 cells by up-regulating the Bax/Bcl-2 ratio and decreasing mitochondrial membrane potential.
Tanshinone IIA (Tan-IIA) may inhibit the growth of human non-small cell lung cancer A549 cells. However, the molecular mechanisms behind this malignancy have yet to be established. In the present study, we examined the effects of Tan-IIA on human small cell lung cancer H146 cells in vitro. The cytotoxicity of Tan-IIA in H146 cells was measured using the MTT assay. Mitochondrial membrane potenti...
متن کاملInduction of endoplasmic reticulum stress by bortezomib sensitizes myeloma cells to DR5-mediated cell death
TNF-related apoptosis-including ligand/Apo2 (TRAIL)-mediated immunotherapy is an attractive anti-tumor modality with high tumor specificity. In order to improve its therapeutic efficacy, we further need to implement a novel maneuver for sensitization of malignant cells to TRAIL. Bortezomib (BTZ), a novel anti-myeloma (MM) agent, potently induces endoplasmic reticulum (ER) stress to cause apopto...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- International journal of oncology
دوره 48 5 شماره
صفحات -
تاریخ انتشار 2016