W346 inhibits cell growth, invasion, induces cycle arrest and potentiates apoptosis in human gastric cancer cells in vitro through the NF-κB signaling pathway.

The therapeutic agent selectively killing cancer cells is urgently needed for gastric cancer treatment. Curcumin has been investigated for its effect on the cancer treatment because of its significant therapeutic potential and safety profile. A synthetic unsymmetry mono-carbonyl compound termed W346 was developed from curcumin. In this study, we investigated the potential antineoplastic effect and mechanism of W346 against human gastric cancer cells. W346 suppressed the proliferation and invasion, blocked cell cycle arrest at G2/M phase, and increased apoptosis in gastric cancer cells, and it presented obviously improved anticancer activity than curcumin. Moreover, W346 effectively inhibited tumor necrosis factor (TNF-α)-induced NF-κB activation by suppressing IKK phosphorylation, inhibiting IκB-α degradation, and restraining the accumulation of NF-κB subunit p65 nuclear translocation. W346 also affected NF-κB-regulated downstream products involved in cycle arrest and apoptosis. In a word, W346 exhibited significantly improved anti-gastric cancer activity over curcumin by targeting NF-κB signaling pathway, and it is likely to be a promising starting point for the development of curcumin-based therapeutic agent.

Peptidomimetic suppresses proliferation and invasion of gastric cancer cells by fibroblast growth factor 2 signaling cascade blockage.

Fibroblast growth factor 2 (FGF2) is closely involved in a variety of tumors, including gastric cancer (GC). FGF2 inhibitors exert good antitumor activity, but no FGF2 inhibitor has been employed for clinical use. To obtain a low-toxicity, stable peptidomimetic (called P29) target to FGF2, the affinity between P29 and FGF2 was detected by surface plasmon resonance. The stability of P29 was measured by high performance liquid chromatography. MTT assay and transwell assay were used to access the proliferative and invasive ability of GC cells, respectively. Western blot assay and flow cytometric analysis were applied to study the mechanism of P29. P29 possessed high affinity with FGF2 and a longer half-life in vitro. P29 suppressed the FGF2-induced proliferation of GC cells. It also inhibited the phosphorylation of FRS2, ERK1/2, and AKT triggered by FGF2 in GC. In addition, P29 blocked GC cell transformation from the G1/G0 phase to the S phase and weakened the invasive capability of GC cells. In this paper, we present a novel FGF2 inhibitor that could exert improved anticancer effect in GC in vitro.

A peptide derivative serves as a fibroblast growth factor 2 antagonist in human gastric cancer.

Fibroblast growth factor 2 (FGF2) plays a critical role in tumorigenesis and progression of solid tumor and is upregulated in gastric carcinoma serum. Therefore, it is regarded as a potential therapeutic target of human gastric cancer. Suppression of bioactivities of FGF2 may contribute to human gastric cancer therapy. Herein, we obtained a novel FGF2-binding peptide derivative (named P32), which originated from a previously isolated P7 peptide with poor stability. We proved that P32, which had a half-life in human plasma up to 12 h, enhanced stability and exerted strong inhibitory effect on FGF2-induced cell proliferation and invasion in human gastric cancer cell lines. Further investigations revealed that the underlying anti-proliferation mechanisms of P32 in vitro included arresting FGF2-stimulated cells at the G0/G1 phase and reducing the activation of AKT and Erk1/2 cascades. The FGF2-binding peptide derivative P32 has improved stability, is relatively safe, and may have therapeutic potential in FGF2-driven gastric cancer.

Niclosamide inhibition of STAT3 synergizes with erlotinib in human colon cancer.

Niclosamide, an anthelmintic drug approved by the US Food and Drug Administration against cestodes, is used to treat tapeworm infection. In this study, we show that niclosamide can potentially inhibit signal transducer and activator of transcription 3 (STAT3) in colon cancer cell lines. Combined inhibition of epidermal growth factor receptor and STAT3 by erlotinib and niclosamide synergistically induces apoptosis and antiproliferation in colon cancer cell lines. Our findings suggest that erlotinib and niclosamide combination provides an effective therapeutic approach to improving the prognosis of colon cancer.

Design, synthesis, and evaluation of asymmetric EF24 analogues as potential anti-cancer agents for lung cancer.

The nuclear factor-kappa B (NF-κB) signaling pathway has been targeted for the therapy of various cancers, including lung cancer. EF24 was considered as a potent inhibitor of NF-κB signaling pathway. In this study, a series of asymmetric EF24 analogues were synthesized and evaluated for their anti-cancer activity against three lung cancer cell lines (A549, LLC, H1650). Most of the compounds exhibited good anti-tumor activity. Among them, compound 81 showed greater cytotoxicity than EF24. Compound 81 also possessed a potent anti-migration and anti-proliferative ability against A549 cells in a concentration-dependent manner. Moreover, compound 81 induced lung cancer cells death by inhibiting NF-κB signaling pathway, and activated the JNK-mitochondrial apoptotic pathway by increasing reactive oxygen species (ROS) generation resulting in apoptosis. In summary, compound 81 is a valuable candidate for anti-lung cancer therapy.

[Study on different onset patterns and perinatal outcomes in severe preeclampsia].

OBJECTIVE: To explore the different clinical onset patterns in severe preeclampsia. METHODS: A prospective observational study was conducted in 173 cases of severe preeclampsia. They were divided into two groups according to the onset of gestational age of severe preeclampsia, early onset of severe preeclampsia (S-PE) (onset < or = 34 weeks) and late onset of S-PE (onset > 34 weeks). Then according to the onset pattern they were subdivided into 4 subgroups: early abrupt onset (10) and early onset with gradual progress of severe preeclampsia (87), late abrupt onset (18) and late onset with gradual progress of severe preeclampsia (58). Clinical characteristics in each subgroup were evaluated. RESULTS: Cases with abrupt onset accounted for 16.2% out of 173 cases of severe preeclampsia (28/173). The incidence of abrupt onset or onset with gradual progress between early and late onset groups was not significantly different (P > 0.05). Whether in early onset group or late onset group, the incidence of serious maternal complications was much higher in abrupt onset subgroups than that in gradual progress subgroups [100.0% (10/10) vs 34.5% (30/87) and 100.0% (18/18) vs 29.3% (17/58); P < 0.001]. The incidence of serious maternal complications was not significantly different between early onset and late onset groups (P > 0.05). The perinatal mortality rate was higher in abrupt onset subgroups compared to gradual progress subgroups both in early onset groups and in late onset ones (72.7% vs 24.3%, P < 0.01; 22.2% vs 4.9%, P < 0.05). The perinatal mortality rate was higher in each subgroups in early onset groups than that in late onset ones respectively (P < 0.01, P < 0.05). The gestational age at delivery was closely associated with perinatal outcomes. When a delimitation of early onset of severe preeclampsia was set at 32-week gestation, perinatal outcome was associated with both gestational age at birth and the onset time of severe preeclampsia. If the cut-off point was set at 34-week gestation, perinatal outcome was associated only with gestational age at birth. CONCLUSIONS: Approximately 16% pregnant women with severe preeclampsia were attacked abruptly and complicated by serious complications. The clinical delimitation of early onset of severe preeclampsia set at 32-week gestation is significantly associated with poor maternal and perinatal outcomes.

A novel double carbonyl analog of curcumin induces the apoptosis of human lung cancer H460 cells via the activation of the endoplasmic reticulum stress signaling pathway.

Curcumin can inhibit the growth of a variety of cancer cells; however, its poor bioavailability and pharmacokinetic profiles, which are attributed to its instability under physiological conditions, have limited its application in anticancer therapy. In the present study, we screened a double carbonyl analog of curcumin (A17) and analyzed its effects and mechanism of inducing apoptosis in human lung cancer H460 cells. The results showed that A17 not only induced CHOP expression in human lung cancer H460 cells, but also induced the apoptosis of H460 cells in a dose-responsive manner, and this effect was related to corresponding activation of some important components in the endoplasmic reticulum (ER) stress-mediated apoptosis pathway. When CHOP was knocked down by specific siRNA, A17-induced cell apoptosis was attenuated, thereby further demonstrating that the apoptotic pathway is ER stress­dependent. Our studies demonstrated that A17 has better stability and antitumor activity than curcumin in H460 cells via an ER stress-mediated mechanism. These results imply that A17 could be further explored as a potential anticancer agent for the treatment of human non-small cell lung cancer (NSCLC).

[Clinical delimitation and expectant management of early onset of severe pre-eclampsia].

OBJECTIVE: To determine the clinical delimitation and to investigate the difference of maternal and perinatal outcome with expectant management of women with early onset of severe preeclampsia. METHODS: Two hundred and fifty-five cases meeting the criteria of severe pre-eclampsia who underwent expectant management were enrolled in this study. Patients were divided into 4 groups: group A (n = 24) with onset before 28 weeks of gestation, group B (n = 50) with onset during 28 - 31 weeks of gestation, group C (n = 34) with onset during 32 - 33 gestational weeks, and group D (n = 147) with onset >or= 34 weeks of gestation. Main outcome measures included prolongation of gestation, perinatal mortality rate, and small for gestational age as well as major complications. RESULTS: The average pregnancy prolongation was (9 +/- 3) days (range 1 to 40), (11 +/- 8) (range 1 to 28), (8 +/- 6) (range 1 to 21), and (5 +/- 4) (range 1 to 21), respectively in groups A, B, C and D. The gestational age at delivery was closely associated with the perinatal outcome. When a cut-off point was set at 34-week gestation, perinatal outcome was only associated with the gestational age at birth. If the cut-off point was set at 32-week gestation, perinatal morbidity and mortality were associated with both gestational age at birth and the onset of severe preeclampsia during pregnancy. CONCLUSIONS: The clinical delimitation of early onset of severe preeclampsia at 32-week gestation is significantly associated with poor maternal and perinatal outcome. Expectant management should be carried out in well-selected patients with severe preeclampsia remote from term, individually.

Anti-Lung Cancer Activity of the Curcumin Analog JZ534 In Vitro.

This study investigated the anticancer effect of the curcumin analog JZ534 on lung cancer cell lines H460, A549, H1975, and HCC827. The antiproliferation effect of JZ534 was measured through the methylthiazoletetrazolium assay, and cell colony formation was observed. Cell cycle and apoptosis were determined by flow cytometry, and the preliminary mechanism was studied by Western blot. Results showed that JZ534 significantly inhibited the vitality and colony formation of lung cancer cells. JZ534 induced the G2/M cell cycle arrest of the cancer cells and suppressed the expression of cycle-related proteins, including cyclin B1 and Cdc2. Meanwhile, JZ534 induced cell apoptosis and upregulated the expression of apoptosis-related proteins, including cleaved caspase-3, Bax, and p53. At the same dose, JZ534 showed better antitumor activity than curcumin. These results suggest that JZ534 exhibits excellent anti-lung cancer activity by inhibiting the growth and inducing the apoptosis of lung cancer cells. Therefore, JZ534 is a promising lead compound for cancer treatment.