Anemarrhena asphodeloides Bunge and its constituent timosaponin-AIII induce cell cycle arrest and apoptosis in pancreatic cancer cells.

Pancreatic cancer is one of the most recalcitrant and lethal of all cancers. We examined the effects of Anemarrhena asphodeloides (AA) and timosaponin-AIII (TAIII), a steroidal saponin present in AA, on pancreatic cancer cell proliferation and aimed to elucidate their potential apoptotic mechanisms of action. Viability assays and cell cycle analysis revealed that both AA and TAIII significantly inhibited pancreatic cancer cell proliferation and cell cycle progression compared to treatment with gemcitabine, the standard chemotherapeutic agent for advanced pancreatic cancer. We identified a dose-dependent increase in caspase-dependent apoptosis and activation of pro-apoptotic PI3K/Akt pathway proteins, with a subsequent downregulation of pro-survival PI3K/Akt pathway proteins, in pancreatic cancer cells treated with AA or TAIII over those treated with gemcitabine.

Circulating PANDER concentration is associated with increased HbA1c and fasting blood glucose in Type 2 diabetic subjects.

AIM: PANcreatic-DERived factor (PANDER, FAM3B) is a novel hormone that regulates glucose levels via interaction with both the endocrine pancreas and liver. Prior studies examining PANDER were primarily conducted in murine models or in vitro but little is known regarding the circulating concentration of PANDER in humans, especially with regard to the association of type 2 diabetes (T2D) or overall glycemic regulation. To address this limitation, we performed a cross-sectional analysis of circulating serum PANDER concentration in association with other hormones that serve as either markers of insulin resistance (insulin and adiponectin) or to metabolic parameters of glycemic control such as fasting HbA1c and blood glucose (FBG). METHODS: Fasting serum was obtained from a commercial biorepository from 300 de-identified adult subjects with 150 T2D and non-T2D adult subjects collected from a population within the United States, respectively, matched on gender, age group and race/ethnicity. Concentration of PANDER, insulin and adiponectin were measured for all samples as determined by commercial ELISA. Metadata was provided for each subject including demography, anthropometry, and cigarette and alcohol use. In addition, fasting blood glucose (FBG) and HbA1c were available on T2D subjects. RESULTS: Multiple linear regression analyses were performed to examine the relationships between circulating log PANDER concentration on HbA1c, fasting glucose, log insulin, log HOMA-ß and log HOMA-IR among T2D subjects and for insulin and adiponectin in non-T2D subjects. A significant linear association was identified between PANDER with fasting HbA1c (ß 0.832 ±â€¯SE 0.22, p = 0.0003) and FBG (ß 20.66 ±â€¯SE 7.43, p = 0.006) within T2D subjects. However, insulin, HOMA-ß, HOMA-IR and adiponectin (p > 0.05) were not found to be linearly associated with PANDER concentration. CONCLUSION: Within T2D subjects, PANDER is modestly linearly associated with increased HbA1c and FBG in a US population. In addition, highest circulating PANDER levels were measured in T2D subjects with HbA1c above 9.9. No association was identified with PANDER and insulin resistance or pancreatic ß-cell function in T2D subjects.