Julie A. Alosi

Pterostilbene inhibits breast cancer in vitro through mitochondrial depolarization and induction of caspase-dependent apoptosis.

BACKGROUND Epidemiologic studies suggest that diets high in fruits and vegetables reduce cancer risk. Resveratrol, a compound present in grapes, has been shown to inhibit a variety of primary tumors. Pterostilbene, an analogue of resveratrol found in blueberries, has both antioxidant and antiproliferative properties. We hypothesized that pterostilbene would induce apoptosis and inhibit breast cancer cell growth in vitro. METHODS Breast cancer cells were treated with graduated doses of pterostilbene. Cell viability was measured by MTT assay. Apoptosis was evaluated via DNA fragmentation assay and TUNEL assay. Apo-ONE caspase-3/7 assay was used to evaluate caspase activity. Flow cytometry was used to evaluate mitochondrial depolarization, superoxide formation, and cell cycle. Students t-test and two-way ANOVA with Bonferroni posttests were utilized for statistical analysis. RESULTS Pterostilbene decreased breast cancer cell viability in a concentration- and time-dependent manner. Pterostilbene treatment increased caspase-3/7 activity and apoptosis in both cell lines. Caspase-3/7 inhibitors completely reversed pterostilbenes effects on cell viability. Pterostilbene treatment triggered mitochondrial depolarization, increased superoxide anion, and caused alteration in cell cycle. CONCLUSIONS Pterostilbene treatment inhibits the growth of breast cancer in vitro through caspase-dependent apoptosis. Mitochondrial membrane depolarization and increased superoxide anion may contribute to the activation downstream effector caspases. Caspase inhibition leads to complete reversal of pterostilbenes effect on cell viability. Further in vitro mechanistic studies and in vivo experiments are warranted to determine its potential for the treatment of breast cancer.

Pterostilbene Inhibits Lung Cancer Through Induction of Apoptosis

BACKGROUND Lung cancer remains the leading cause of cancer mortality in the United States. Resveratrol is a potent antioxidant found in grapes that inhibits several types of cancer, including lung cancer. Herein, we investigated the effects of pterostilbene, an analog of resveratrol found in blueberries, on lung cancer, in vitro. We hypothesized that pterostilbene would inhibit lung cancer cell growth in vitro by a pro-apoptotic mechanism. METHODS Two lung cancer cell lines (NCI-H460 and SK-MES-1) were cultured using standard techniques. Cells were treated with increasing doses of pterostilbene (10-100 microM). Cell viability was measured at 24, 48, and 72h using a MTT assay. Apo-ONE Caspase-3/7 assay was used to evaluate caspase activity. T-test and two-way ANOVA were used for statistical analysis. RESULTS Pterostilbene significantly decreased cell viability in lung cancer cells in a concentration- and time-dependent manner (P<0.001). Concentrations greater than 20 microM of pterostilbene produced significant growth inhibition by 72h (P<0.001). Apoptosis and caspase-3/7 activity were significantly increased by pterostilbene treatment (P<0.05). CONCLUSIONS Pterostilbene inhibits growth via apoptosis induction in vitro. Further in vitro mechanistic studies and in vivo experiments are warranted to determine the potential role for pterostilbene in lung cancer treatment or prevention.

Effects of pterostilbene on melanoma alone and in synergy with inositol hexaphosphate

BACKGROUND Pterostilbene and inositol-6-phosphate (IP6) have been shown to inhibit melanoma growth in vitro. However, pterostilbenes mechanism of action has not been clearly demonstrated. We aimed to further investigate the mechanism of action for pterostilbene and to determine whether combination treatment with IP6 produced synergistic growth inhibition. METHODS Melanoma cells were treated with increasing doses of pterostilbene, IP6, or combinations thereof. Cell viability was measured at 24 hours, 48 hours, and 72 hours using a MTT assay. Caspase activity and vascular endothelial growth factor (VEGF) production were measured using enzyme-linked immunosorbent assay (ELISA). Analysis of variance (ANOVA) and t tests were used for statistical analysis. RESULTS Pterostilbene inhibits melanoma growth in vitro in association with increased effector caspase activity. Combination treatment with inositol hexaphosphate produces synergistic growth inhibition, greater than either treatment alone. CONCLUSIONS Pterostilbene produces caspase-dependent apoptosis in melanoma cell lines. Combination treatment with IP6 produces synergistic growth inhibition. Both compounds have significant potential for a therapeutic role in the treatment of melanoma.

Peptide YY Mediates Inhibition of Tumor Growth and Inflammation

Peptide YY (PYY) orchestrates the functions of the gut and the pancreas by regulating growth, digestion and absorption. In addition to its physiological role, PYY exhibits immune and antitrophic properties in the pancreas by decreasing cytokine and amylase release. Although the exact mechanism(s) of action are still incompletely understood, PYY interacts at the acinar level with numerous intracellular transcription factors. In addition to ameliorating pancreatic inflammation, novel synthetic analogs of PYY have been developed that are potent inhibitors of pancreatic cancer proliferation, in vitro and in vivo. Additionally, PYY and its analogs have been shown to inhibit the growth of breast, esophagus, and gastric cancer in vitro. We, herein, plan to review some of the methods employed in the laboratory while investigating the utility of PYY in the treatment of inflammation and cancer.

Su1844 Duodenal Adenocarcinoma: Has Survival Outcome Profile Changed in Recent Years?

Background: Double Balloon Enteroscopy (DBE) is a surgery sparing procedure to remove ingested foreign bodies which pass beyond the duodenum but have prolonged small bowel passage or get lodged in the small bowel. Aim: To investigate the outcome and safety of DBE for removal of ingested foreign bodies from the small bowel. Methods: 1296 patients underwent 1747 DBE between February 2009 and September 2013 at a single tertiary center of which 22 patients underwent 20 upper DBE and 13 lower DBE for removal of ingested foreign bodies. Data was abstracted by retrospective chart review. Primary outcome was the retrieval success and secondary outcome the complication rate. Results: 22 patients (mean age 54.3 years, SD 19.1) underwent DBE for retrieval of a pill camera (n=12), distal migrated biliary or pancreatic stents (n=5) and accidently or in suicidal attempt ingested foreign bodies (spoon, nail, fish hook) (n=5). 12 patients (57%) underwent a CT scan prior DBE to localize the foreign body (pill camera n=2, stent n=5, ingested foreign body n=5). Only 7 patients had known underlying medical conditions affecting the small bowel (Crohns disease n=3, previous bowel surgery n=4). In addition to 3 patients with known Crohns disease DBE diagnosed 4 additional patients with small bowel Crohns disease, 7 nonsteroidal anti-inflammatory drug (NSAID) inducing strictures and 1 anastomotic stricture. Retrieval of the foreign body was successful in 19 patients (86%) using Roth net (50%), snare (30%) or forceps (20%). 6 patients required small bowel balloon dilation prior removal of the foreign body. 3 patients (13%) (2 pill camera and 1 nail) failed retrieval of the foreign body. Two underwent surgery and 1 patient (ingested nail) who was not a surgical candidate due to frozen abdomen passed the nail spontaneously at a later point. Of 33 DBE 1 procedure (3%) was complicated by small bowel perforation following a successful removal of the pill camera lodged at a Crohns stricture requiring emergent surgical intervention. Limitations: Single center, retrospective study, heterogeneous patient population. Conclusion: To our knowledge this is the largest cohort study of patients with lodged foreign bodies in the small bowel who underwent DBE. DBE has a high success rate of foreign body retrieval in light of a relative low complication rate. Discussion: A success rate of 86%with a complication rate of 3% justifies patient transfer to a high expertise DBE center for removal of lodged foreign bodies in the small bowel prior attempting a surgical intervention as long as the patient remains stable.