A recent study showned that complementary medicine is gradually gaining wide acceptance. In the present study, the herbal mixture extract (H3) composed of 3 oriental herbal plants was investigated for anticancer activity in vitro and in vivo. H3 inhibited PANC1 cell growth by promoting G0/G1 arrest (11% increase) and apoptotic cell death (9% increase). H3 also suppressed stem cell-like side population cells (4% decrease) and migration activity (24% decrease). In contrast, gemcitabine decreased side population cells and migration activity by 3 and 11%, respectively. These effects of H3 and gemcitabine were further studied by examining the expression of apoptosis-associated genes (CXCR4, JAK2 and XIAP) and stem cell-associated genes (ABCG2, POU5F1 and SOX2). We also found that H3 suppressed tumor growth by 46% in a PANC1‑xenograft model, while gemcitabine caused a 36% decrease. The antitumor effects of H3 were confirmed by western blot analysis for COX-2 and cytochrome c expression. Furthermore, necrotic cell death and erythrocyte-containing cavities were detected in tumor tissue by hematoxylin and eosin (H&E) staining. Notably, the combinatorial therapy (H3 and gemcitabine) increased tumor growth compared to that in the control. In conclusion, the present study shows that H3 has promise as a therapeutic agent against pancreatic cancer and its cancer stem cells.

Silver materials may be toxic in humans because they can enter the body and accumulate, typically in the lungs. We hypothesized that the cytotoxicity of naïve silver materials is affected by their size and shape. Our in vitro assays revealed that the overall toxicity was in the following order: submicro-particles > wires > micro-particles. These results contrast with previous studies, which showed that silver wires are the most toxic among the three tested materials, possibly due to differences in cell lines. Evaluations of in vivo pulmonary toxicity revealed eryptosis in the cavity lining of the lung sections. The observed eryptosis was consistent with the in vitro results. Our results indicate that silver materialinduced cytotoxicity must be measured and compared using various methods.