MATERIALS AND METHODS: In the present study, the anticancer effects and the mechanisms of action of 17βH-neriifolin (cardiac glycoside) were evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and a proteomic approach in treated and non-treated SKOV-3 ovarian cancer cells.
RESULTS: 17βH-neriifolin was found to be active with IC50 values of 0.01 ± 0.001 in SKOV-3 ovarian cancer cell line, as evaluated by the sulforhodamine B (SRB) assay. RESULTS from TUNEL assay indicated that 17βH-neriifolin caused apoptosis in SKOV-3 cells in a dose-dependent manner. Based on differential analysis of treated and non-treated SKOV-3 two-dimensional electrophoresis (2-DE) profiles, four proteins, namely vimentin (VIM), pyruvate kinase, muscle (PKM), heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) and transgelin (TAGLN1) were identified to be involved in apoptosis. Other proteins including piggybac transposable element derived 5 (PGBD5), DENN/MADD domain containing 2D (DENND2D) and formin-like 1(FMNL) have also been identified to be associated in SKOV-3 cell death induced by 17βH-neriifolin.
CONCLUSION: These findings may provide new insights on the potential of 17βH-neriifolin's mechanism of action in killing ovarian cancer cells.
METHODS: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations.
RESULTS: CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 versus CRP ≤1 mg/L was associated with higher overall EOC risk [OR, 1.67 (1.03-2.70)]. We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference [e.g., IL6: waist ≤80: ORlog2, 0.97 (0.81-1.16); waist >88: ORlog2, 1.78 (1.28-2.48), Pheterogeneity ≤ 0.01].
CONCLUSIONS: Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity.
IMPACT: Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.