In vitro and in vivo anti-leukemic effects of cladoloside C2 are mediated by activation of Fas/ceramide synthase 6/p38 kinase/c-Jun NH2-terminal kinase/caspase-8.

We previously demonstrated that the quinovose-containing hexaoside stichoposide C (STC) is a more potent anti-leukemic agent than the glucose-containing stichoposide D (STD), and that these substances have different molecular mechanisms of action. In the present study, we investigated the novel marine triterpene glycoside cladoloside C2 from Cladolabes schmeltzii, which has the same carbohydrate moiety as STC. We assessed whether cladoloside C2 could induce apoptosis in K562 and HL-60 cells. We also evaluated whether it showed antitumor action in mouse leukemia xenograft models, and its molecular mechanisms of action. We investigated the molecular mechanism behind cladoloside C2-induced apoptosis of human leukemia cells, and examined the antitumor effect of cladoloside C2 in a HL-60 and K562 leukemia xenograft model. Cladoloside C2 dose- and time-dependently induced apoptosis in the analyzed cells, and led to the activation of Fas/ceramide synthase 6 (CerS6)/p38 kinase/JNK/caspase-8. This cladoloside C2-induced apoptosis was partially blocked by specific inhibition by Fas, CerS6, and p38 siRNA transfection, and by specific inhibition of JNK by SP600125 or dominant negative-JNK transfection. Cladoloside C2 exerted antitumor activity through the activation of Fas/CerS6/p38 kinase/JNK/caspase-8 without showing any toxicity in xenograft mouse models. The antitumor effect of cladoloside C2 was reversed in CerS6 shRNA-silenced xenograft models. Our results suggest that cladoloside C2 has in vitro and in vivo anti-leukemic effects due to the activation of Fas/CerS6/p38 kinase/JNK/caspase-8 in lipid rafts. These findings support the therapeutic relevance of cladoloside C2 in the treatment of human leukemia.

Formaldehyde and heavy metal migration from rubber and metallic packaging/utensils in Korea.

The aim of this study was to determine the non-intentionally added substances--formaldehyde and trace metals--at 4% acetic acid conditions in rubber and metallic packaging/utensils. The temperature effect on migration in rubber and metallic packaging/utensils was monitored at 60 °C and 100 °C under acidic (pH < 3) circumstances. The concentrations were: formaldehyde--23.1 µg kg⁻¹, lead--13.41 µg kg⁻¹, cadmium--0.15 µg kg⁻¹, total arsenic--2.02 µg kg⁻¹ and nickel--2.92 µg kg⁻¹ at 60 °C and formaldehyde--148.9 µg kg⁻¹, lead--17.04 µg kg⁻¹, cadmium--0.14 µg kg⁻¹, total arsenic--7.25 µg kg⁻¹ and nickel--8.7 µg kg⁻¹ at 100 °C. A significant difference was noticed in formaldehyde and total arsenic between both temperatures (p < 0.01), which was not present in other trace metals. In conclusion, formaldehyde and total arsenic were more sensitive with cooking temperature than the other metals.

Determination of 4-Methylimidazole and 2-Acetyl-4()- tetrahydroxybutylimidazole in Caramel Color and Processed Foods by LC-MS/MS.

In this study, the quick HPLC-MS/MS method for the simultaneous separation of 2-acetyl-4(5)-tetrahydrox-ybuthylimidazole (THI) and 4-(5)-methylimidazole (4-MI) in alkaline medium was used for caramel color and processed foods in Korea. After a simple sample pretreatment, 51 4-MI-labeled samples were positive for 4-MI and 2 also contained THI. The concentration of 4-MI was 260.5 ~ 24,499.3 µg/kg in caramel color, less than LOD ~ 1,712.5 µg/kg in sauce, 1,242.3, 5,972.2 µg/kg in balsamic vinegar, 2,118.3 ~ 5,802.4 µg/kg in complex seasoning, 82.7 ~ 5,110.6 µg/kg in curry, and 29.9 ~ 464.4 µg/kg in soft drinks. The recovery rate of 4-MI was 97.1 ~ 111.0% in sauce and 81.9 ~ 110.0% in powder and that of THI was 83.6 ~ 106.4% in sauce and 61.2 ~ 99.4% in powder. Our results concluded a safe amount of 4-MI and THI compared to the limit of Korea additive code but the processed foods do not have a limit of caramel color and 4-MI in Korea. Therefore, research and monitoring of 4-MI and THI is needed for processed foods in Korea.