Lanatoside C inhibits human cervical cancer cell proliferation and induces cell apoptosis by a reduction of the JAK2/STAT6/SOCS2 signaling pathway.

Cervical cancer is one of the leading causes of cancer-associated mortality in gynecological diseases and ranks third among female cancers worldwide. Although early detection and vaccination have reduced incidence rates, cancer recurrence and metastasis lead to high mortality due to the lack of effective medicines. The present study aimed to identify novel drug candidates to treat cervical cancer. In the present study, lanatoside C, an FDA-approved cardiac glycoside used for the treatment of heart failure, was demonstrated to have anti-proliferative and cytotoxic effects on cervical cancer cells, with abrogation of cell migration in a dose-dependent manner. Lanatoside C also triggered cell apoptosis by enhancing reactive oxygen species production and reducing the mitochondrial membrane potential, which induced cell cycle arrest at the S and G2/M phases. Furthermore, lanatoside C inhibited the phosphorylation of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 6 (STAT6), while inducing the expression of suppressor of cytokine signaling 2, a negative regulator of JAK2-STAT6 signaling. Taken together, the results of the present study suggest that lanatoside C suppresses cell proliferation and induces cell apoptosis by inhibiting JAK2-STAT6 signaling, indicating that lanatoside C is a promising agent for the treatment of cervical cancer.

Kaempferol Sensitizes Human Ovarian Cancer Cells-OVCAR-3 and SKOV-3 to Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Induced Apoptosis via JNK/ERK-CHOP Pathway and Up-Regulation of Death Receptors 4 and 5.

BACKGROUND Ovarian cancer is the most common gynecological malignancies in women, with high mortality rates worldwide. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) superfamily which preferentially induces apoptosis of cancer cells. However, acquired resistance to TRAIL hampers its therapeutic application. Identification of compounds that sensitize cancer cells to TRAIL is vital in combating resistance to TRAIL. The effect of kaempferol, a flavonoid enhancing TRAIL-induced apoptosis in ovarian cancer cells, was investigated in this study. MATERIAL AND METHODS The cytotoxic effects of TRAIL (25 ng/mL) and kaempferol (20-100 µM) on human ovarian cancer cells OVCAR-3 and SKOV-3 were assessed. Effect of kaempferol on the expression patterns of cell survival proteins (Bcl-xL, Bcl-2, survivin, XIAP, c-FLIP) and apoptotic proteins (caspase-3, caspase-8, caspase-9, Bax) were studied. The influence of kaempferol on expression of DR4 and DR5 death receptors on the cell surface and protein and mRNA levels was also analyzed. Apoptosis following silencing of DR5 and CHOP by small interfering RNA (siRNA), and activation of MAP kinases were analyzed as well. RESULTS Kaempferol enhanced apoptosis and drastically up-regulated DR4, DR5, CHOP, JNK, ERK1/2, p38 and apoptotic protein expression with decline in the expression of anti-apoptotic proteins. Further transfection with siRNA specific to CHOP and DR5 indicated the involvement of CHOP in DR5 up-regulation and also the contribution of DR5 in kaempferol-enhanced TRAIL-induced apoptosis. CONCLUSIONS Kaempferol sensitized ovarian cancer cells to TRAIL-induced apoptosis via up-regulation of DR4 and DR5 through ERK/JNK/CHOP pathways.

Curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway.

We have previously reported that curcumin inhibits urothelial tumor development in a rat bladder carcinogenesis model. In this study, we report that curcumin inhibits urothelial tumor development by suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway. Curcumin inhibits IGF2 expression at the transcriptional level and decreases the phosphorylation levels of IGF1R and IRS-1 in bladder cancer cells and N-methyl-N-nitrosourea (MNU)-induced urothelial tumor tissue. Ectopic expression of IGF2 and IGF1R, but not IGF1, in bladder cancer cells restored this process, suggesting that IGF2 is a target of curcumin. Moreover, introduction of constitutively active AKT1 abolished the inhibitory effect of curcumin on cell proliferation, migration, and restored the phosphorylation levels of 4E-BP1 and S6K1, suggesting that curcumin functions via suppressing IGF2-mediated AKT/mTOR signaling pathway. In summary, our results reveal that suppressing IGF2 and IGF2-mediated PI3K/AKT/mTOR signaling pathway is one of the mechanisms of action of curcumin. Our findings suggest a new therapeutic strategy against human bladder cancer caused by aberrant activation of IGF2, which are useful for translational application of curcumin.

[Comparison of texture distribution of cold rolled DC and CC AA 5052 aluminum alloy at different positions through thickness direction by XRD].

To provide gist of DC AA 5052 and CC AA 5052 aluminum alloy to industry production and application, the texture variation of cold rolled sheets through thickness direction was studied by X-ray diffraction method, and the difference in texture at surface, quarter and center layer was analyzed. The hot plates of direct chill cast (DC) AA 5052 and continuous cast (CC) AA 5052 aluminum alloy were annealed at 454 degrees C for 4 hours and then cold rolled to different reductions. The strength and volume fraction of the fiber in CC AA 5052 aluminum alloy is larger than in DC AA 5052 aluminum alloy after same rolling reduction The volume fraction of the recrystallization texture cube in the CC AA 5052 aluminum alloy is less than in the DC AA 5052 aluminum alloy, which result in that CC AA 5052 aluminum alloy needs less cold rolling reduction than DC AA 5052 aluminum alloy for generating the texture with same intensity and volume fraction at surface layer, quarter layer and center layer. The manufacturability and performance of CC AA 5052 aluminum alloy is superior to DC AA 5052 aluminum alloy for use in stamping.

Effects of curcumin on bladder cancer cells and development of urothelial tumors in a rat bladder carcinogenesis model.

Curcumin, a well-known dietary pigment derived from Curcuma longa, inhibited growth of several types of malignant cells both in vivo and in vitro. Its effects on cell proliferation and the induction of apoptosis in human bladder cancer cell lines and intravesical activity in a rat bladder tumor model were studied. Exposure of human bladder cancer cells to curcumin resulted in the induction of apoptotic cell death and caused cells to arrest in the G2/M phase. The anti-apoptotic Bcl-2 and Survivin protein was downregulated by the curcumin treatment together with enhancement of the Bax and p53 expression. The inhibitory activities of curcumin were stronger than those of cisplatin and could not be prevented by catalase pretreatment in T24 cells. Clonal assay indicated large-dose and short-term curcumin was lethal to bladder cancer cells. Moreover, the in vivo study revealed curcumin did induce apoptosis in situ, inhibit and slow the development of bladder cancer. These observations suggest that curcumin could prove an effective chemopreventive and chemotherapy agent for bladder cancer.