Synergistic effect of the herbal mixture C5E on gemcitabine treatment in PANC­1 cells.

The present study aimed to determine the anticancer effect of the herbal mixture extract C5E in the pancreatic cancer cell line, PANC­1, in the absence or presence of gemcitabine treatment, a chemotherapeutic drug used for the treatment of pancreatic cancer. The anticancer effects of C5E, gemcitabine and C5E plus gemcitabine in PANC­1 cells following 72 h of treatment were investigated. The effect of each treatment on cell cycle arrest, apoptosis and the proportion of side population (SP) cells was determined using flow cytometric analysis following propidium iodide (PI), Annexin V­FITC/PI double staining and Hoechst 33342 staining, respectively. SP cells share similar characteristics to cancer stem­like cells, and a reduction in the SP is considered to be indicative of an anticancer effect. The percentage of SP cells and the cell viability of general PANC­1 cells were significantly decreased in response to all treatments. The percentage of SP cells was reduced from 8.2% (control) to 3.9, 7.2 and 5.1% following the treatment with C5E, gemcitabine and the co­treatment, respectively. All three treatments were discovered to inhibit cell viability by arresting the cell cycle at the S phase and promoted cell death by inducing early apoptosis, with the levels of apoptosis being increased from 1.9% (control) to 7.3, 2.5 and 12.0% following the treatment with C5E, gemcitabine and the co­treatment, respectively. The mRNA expression levels of sonic hedgehog, which is implicated in the development of certain types of cancer, were downregulated to a greater extent following the co­treatment with C5E and gemcitabine compared with the treatment with either C5E or gemcitabine alone. As the co­treatment with gemcitabine and C5E was more effective than each individual treatment, the present study suggested that the combined treatment may exhibit synergistic effects in PANC­1 cells.

Effect of branched-chain amino acid supplements on muscle strength and muscle mass in patients with liver cirrhosis.

OBJECTIVE: The aim of this study was to assess the effect of branched-chain amino acid (BCAA) supplements on muscle strength and muscle mass in patients with liver cirrhosis. PATIENTS AND METHODS: We carried out a single-center, prospective study of adult cirrhotic patients receiving nutrition therapy at Shonan Kamakura General Hospital. A 28-day pretreatment observation period was followed by a 24-week treatment period. Patients who fulfilled the treatment criteria received one package of oral BCAA supplement powder twice a day and the response was evaluated. A responder to BCAA in muscle strength and muscle mass was defined as a patient with an increased skeletal muscle mass index and hand grip assessed 24 weeks after drug treatment commenced. RESULTS: Eighty-two patients fulfilled our criteria and completed the treatment. In terms of muscle strength, there were 59 (72.0%) responders to BCAA supplementation with a significant increase in hand grip from before treatment (22.2±6.3 kg) to after treatment (23.9±6.4 kg) (P<0.001). In terms of muscle mass, 36 (43.9%) patients responded to BCAA with a slight decrease in skeletal muscle mass index from before treatment (7.40±1.62) to after treatment (7.30±1.49) (P=0.333). CONCLUSION: BCAA supplementation improved low muscle strength in patients with chronic liver disease, but did not increase muscle mass during the treatment period.

Antitumor effects of herbal mixture extract in the pancreatic adenocarcinoma cell line PANC1.

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 PANC1­xenograft 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.