In addition, MHCC-LM3 has a high ABCG2 expression37 We found tha

In addition, MHCC-LM3 has a high ABCG2 expression.37 We found that lupeol shrank the tumor volume by induction of apoptosis. Moreover, lupeol did not show signs of toxicity; importantly, the other

organs of the mice showed no histological damage or necrosis. Treatment with lupeol alone had an effect similar to that of cisplatin plus doxorubicin in suppressing tumor growth. However, combined treatment with cisplatin and doxorubicin had severe side effects in terms of decreasing body weight. Our data have shown that lupeol was as potent as cisplatin in terms of decreasing tumor volume. Lupeol combined with a low dose of cisplatin and doxorubicin could effectively suppress tumor growth. More importantly, lupeol given with a low dose of

cisplatin and doxorubicin was approximately 11-fold more potent than cisplatin and doxorubicin alone and had no side effects in this animal model. To confirm the in vitro mechanism of lupeol, Bcl-2 inhibitor corresponding RNAs from each group were extracted and quantified by way of quantitative polymerase chain reaction. Enrichment of the stem cell population was shown by the increased levels of CD133 and ABCG2 upon treatment with chemotherapeutic drugs alone. These results further support enrichment of the T-IC population found in lung cancer following chemotherapy.38 Consistent with our in vitro data, lupeol-treated tumors had decreased expression of CD133 and ABCG2 compared with control tumors. If the T-IC hypothesis is correct, NVP-LDE225 ic50 this result could explain the chemosensitization effect of lupeol. To our knowledge, this study is the first in vitro and in vivo demonstration of the anti–T-IC efficacy of lupeol, which acts by modulating the PTEN–Akt–ABCG2 pathway against HCC. Lupeol exerted a significant synergistic and cytotoxic effect without adverse effects when combined with low doses of

cisplatin and doxorubicin. Overall, these findings have provided evidence that lupeol may be a dietary phytochemical that has the potential to target liver T-ICs. Additional Supporting Information may be found in the online version of this article. “
“Introduction: P4 ATPases are lipid flippases involved in transport of phospholipids from the exoplasmic to the cytosolic leaflet MCE of biological membranes. Deficiency of the P4 ATPase ATP8B1 causes progressive familial intrahepatic cholestasis type 1 in men. We have previously shown that the cholestasis in ATP8B1 deficiency originates at the canalicular membrane. Recently it was shown that loss of the P4 ATPase ATP11C in mice leads to unconjugated hypercholanemia (Siggs et al, 2011). Aim: To study whether ATP11C deficiency in mouse liver interferes with the activity of the basolateral uptake transporter for unconjugated bile salts, OATP1B2. Methods: ATP11C deficient mice were generated by chemical mutagenesis (Siggs et al, 2011).

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