Inhibitory Effect of Oat Bran Ethanol Extract on Survival and Gemcitabine Resistance of Pancreatic Cancer Cells.

Pancreatic cancer (PC) is one of the most aggressive malignancies in the world. Gemcitabine (Gem), a nucleoside pyrimidine analogue, is a first-line chemotherapeutic drug for PC, but the tumor response rate of Gem is very low and resistance to Gem has emerged as a major problem in the treatment of PC. Oat bran, used as animal and human food, has been found to be beneficial to health. In this study, effects of oat bran ethanol extract (OBE) on PC cells and Gem-resistant PC cells were investigated in vitro. OBE decreased cell survival and colony forming ability of PC cells, without any cytotoxicity on the normal pancreatic cells. Flow cytometry analysis and TUNEL assay showed that the OBE reduced G1/S phase transition and induced death in PC cells through AMPK activation and downregulation of JNK. Additionally, OBE could overcome Gem resistance through reduction in RRM1/2 expression and showed synergistic effect by combinatorial treatment with Gem on Gem-resistant PC cells. Additionally, LC-MS data showed that avenacoside A was a component of OBE. Thus, this study elucidated the anti-proliferative effect of OBE and synergistic effect of OBE with Gem on PC cells and Gem-resistant cells.

α, γ-Mangostins Induce Autophagy and Show Synergistic Effect with Gemcitabine in Pancreatic Cancer Cell Lines.

Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of α-mangostin (αM) and γ-mangostin (γM) extracted from the pericarp of Garcinia mangostana L.. Both αM and γM reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels. They also induced autophagy by increasing levels of microtubule-associated protein 1A/1B light chain 3B (LC3II) in both cell lines while decreasing sequestosome 1 (p62) in MIA PaCa-2. Both αM and γM induced autophagy through increasing phosphorylation levels of AMP-activated protein kinase (p-AMPK) and p38-mitogen activated protein kinase (p-p38) while decreasing phosphorylation level of mammalian target of rapamycin complex 1 (p-mTOR). Of various microRNAs (miRNA), miR-18a was found to be a putative regulatory miRNA for autophagy induced by αM or γM. In combination with gemcitabine, a compound frequently used in pancreatic cancer treatment, αM and γM showed synergistic anti-cancer effects in MIA PaCa-2. Collectively, these results suggest that αM and γM can induce apoptosis and autophagy in pancreatic cancer cells and that their anti-cancer effect is likely to be associated with miR-18a. In conclusion, αM and γM might be used as a potential new therapy for pancreatic cancer.

Induction of MiR-21 by Stereotactic Body Radiotherapy Contributes to the Pulmonary Fibrotic Response.

Radiation-induced lung fibrosis, the most serious effect of lung cancer radiotherapy on normal tissue, remains a major technical obstacle to the broader application of radiotherapy to patients with lung cancer. This study describes the use of an image-guided irradiation system in mice mimicking stereotactic body radiotherapy (SBRT) to examine the molecular features of chronic fibrotic response after radiation injury. MicroRNA (miR) array analysis of injured pulmonary tissue identified a set of miRs whose expression was significantly increased in damaged lung tissue. In particular, miR-21 expression was increased at the radiation injury site, concurrent with collagen deposition. Although the inhibition of miR-21 by its specific inhibitor anti-miR-21 only marginally affected endothelial-mesenchymal transition (EndMT) in lung endothelial cells, this inhibition significantly reduced collagen synthesis in lung fibroblasts. Furthermore, ectopic expression of miR-21 was sufficient to promote a fibrotic response in lung fibroblasts, enhancing Smad2 phosphorylation concurrent with Smad7 downregulation. These findings indicate that the induction of miR-21 expression is responsible for fibrotic responses observed in mesenchymal cells at the injury site through the potentiation of TGF-ß signaling. Local targeting of miR-21 at the injured area could have potential therapeutic utility in mitigating radiation-induced lung fibrosis.