Dietary Garcinol Arrests Pancreatic Cancer in p53 and K-ras Conditional Mutant Mouse Model.

Pancreatic cancer (PC) patients have poor prognosis and survival rate. Gemcitabine, the drug of choice has a dismal 15% response rate. Earlier, we reported that Garcinol alone and in combination with gemcitabine showed a dose-dependent favorable response on PC cell lines. This study probes the in vivo effects of dietary Garcinol on PC progression in transgenic PC mice (KPC; K-ras and p53 conditional mutant). KPC male mice were divided into: KC- Control diet; KGr-0.05% Garcinol diet; KGm-Gemcitabine injected; KGG - Garcinol diet + Gemcitabine injected groups. Changes in tumor progression, toxicity, or cell morphology were monitored by magnetic resonance imaging, Fore-stomach, and blood smear, respectively. Pancreatic Intraepithelial Neoplasia (mPanIN) grading with hematoxylin and eosin (H&E) staining was conducted on pancreas and validated by immunohistochemistry. The KGr group showed improved survival, no observable toxicity with marked reduction in papilloma formation in the fore-stomach, and a higher ratio of NK and NKT cells compared to Non-NK lymphocytes. Additionally, the KGr, KGm, and KGG groups showed reduction in tumor volumes and reduced number of advanced mouse PanIN3. Dietary Garcinol alone and in combination with gemcitabine retarded the progression of PC in transgenic PC mice, arresting the cancer in the earlier stages, improving prognosis and survival.

Oil palm phenolics (OPP) inhibit pancreatic cancer cell proliferation via suppression of NF-κB pathway.

BACKGROUND: Oil palm phenolics (OPP) or Palm Juice (PJ), a water soluble extract from the palm fruit (Elaies guineensis) has been documented to have anti-carcinogenic activities in various cancer types. MATERIALS AND METHODS: To investigate OPP effects in pancreatic cancer (PaCa) cells, two PaCa cell lines (PANC-1 and BxPC-3) were treated with different OPP doses. The anti-proliferative, apoptotic and anti-invasive properties of OPP were evaluated using MTS, cytoplasmic histone-DNA fragmentation and matrigel invasive assays, respectively. RESULTS: OPP suppressed PaCa proliferation in a dose-dependent manner. Its anti-invasive effects were validated by decreased expressions of MMP-9 and VEGF. Cell-cycle analysis demonstrated that cells were arrested in the S phase. OPP-induced apoptosis was associated with decrease in survivin and Bcl-XL expressions and increased expression of cleaved caspase-3, caspase-9 and PARP. CONCLUSION: Overall, our results demonstrate the anti-tumor effects of OPP on PaCa cells, providing initial evidence towards its potential therapeutic use.