review of literature on clinical pancreatology - The Pancreapedia

CurcuminCurcumin has been shown to inhibit the growth <strong>of</strong> various types <strong>of</strong> cancer cells; however, atconcentrations much above the clinically achievable levels in humans. The concentration <strong>of</strong>curcumin achieved in the plasma after oral administration in humans was estimated to bearound 1.8 microM. Now it was reported that treatment <strong>of</strong> BxPC-3 human pancreatic cancercells with a low and single exposure <strong>of</strong> 2.5 microM curcumin for 24 h causes significantarrest <strong>of</strong> cells in the G2/M phase and induces significant apoptosis. Immunoblot studiesrevealed increased phosphorylation <strong>of</strong> H2A.X at Ser-139 and Chk1 at Ser-280 and adecrease in DNA polymerase-beta level in curcumin-treated cells. Phosphorylation <strong>of</strong> H2A.Xand Chk1 proteins are an indicator <strong>of</strong> DNA damage whereas DNA polymerase-beta plays arole in the repair <strong>of</strong> DNA strand breaks. Normal immortalised human pancreatic ductalepithelial (HPDE-6) cells remained unaffected by curcumin treatment. In addition, we alsoobserved a significant increase in the phosphorylation <strong>of</strong> Chk1 at Ser-345, Cdc25C at Ser-216 and a subtle increase in ATM phosphorylation at Ser-1981. Concomitant decrease in theexpressions <strong>of</strong> cyclin B1 and Cdk1 were seen in curcumin-treated cells. Further, curcumintreatment caused significant cleavage <strong>of</strong> caspase-3 and PARP in BxPC-3 but not in HPDE-6cells. Silencing ATM/Chk1 expression by transfecting BxPC-3 cells with ATM or Chk1-specific SiRNA blocked the phosphorylation <strong>of</strong> ATM, Chk1 and Cdc25C and protected thecells from curcumin-mediated G2/M arrest and apoptosis. The study reflects the critical role<strong>of</strong> ATM/Chk1 in curcumin-mediated G2/M cell cycle arrest and apoptosis in pancreaticcancer cells [567].AloeThe recent advances in the analysis <strong>of</strong> tumor immunobiology suggest the possibility <strong>of</strong>biologically manipulating the efficacy and toxicity <strong>of</strong> cancer chemotherapy by endogenous orexogenous immunomodulating substances. Aloe is one <strong>of</strong> the <strong>of</strong> the most important plantsexhibiting anticancer activity and its antineoplastic property is due to at least three differentmechanisms, based on antiproliferative, immunostimulatory and antioxidant effects. Theantiproliferative action is determined by anthracenic and antraquinonic molecules, while theimmunostimulating activity is mainly due to acemannan. A study was planned to include 240patients with metastatic solid tumor who were randomized to receive chemotherapy with orwithout Aloe. According to tumor histotype and clinical status, lung cancer patients weretreated with cisplatin and etoposide or weekly vinorelbine, colorectal cancer patients receivedoxaliplatin plus 5-fluorouracil (5-FU), gastric cancer patients were treated with weekly 5-FUand pancreatic cancer patients received weekly gemcitabine. Aloe was given orally at 10 mlthrice/daily. The percentage <strong>of</strong> both objective tumor regressions and disease control wassignificantly higher in patients concomitantly treated with Aloe than with chemotherapy alone,as well as the percent <strong>of</strong> 3-year survival patients [568].GinsengSprague-Dawley rats and ginseng from the roots <strong>of</strong> a 6-year-old fresh Panax ginseng C. A.Meyer plant were used in this study. Pancreatitis was induced by intraperitoneal injection <strong>of</strong>diethyldithiocarbamate for 4 weeks. Korean red ginseng was fed orally to rats for the next 3weeks. At week 7, all rats were killed, and pancreatic tissues were analyzed. The resultssuggest that KRG has antioxidant therapeutic effects on superoxide dismutase inhibitorinducedpancreatitis by inhibition <strong>of</strong> nuclear factor kappaB [569].