Arsenic trioxide (ATO) has been identified as an effective treatment for acute promyelocytic leukemia (APL) but is much less effective against solid tumors such as hepatocellular carcinoma (HCC). In the search for ways to enhance its therapeutic efficacy against solid tumors, we have examined its use in combination with a novel derivative of β-elemene, N-(β-elemene-13-yl)tryptophan methyl ester (ETME). Here we report the effects of the combination on cell viability, apoptosis, the cell cycle and mitochondria membrane potential (MMP) in HCC SMMC-7721 cells. We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis. The combination also decreased the MMP, down-regulated Bcl-2 and pro-proteins of the caspase family, and up-regulated Bax and BID, all of which were reversed by the p53 inhibitor, pifithrin-α. In addition, the combination induced cell cycle arrest at the G2/M phase and reduced tumor volume and weight in an xenograft model of nude mice. Overall, the results suggest that ETME in combination with ATO may be useful in the treatment of HCC patients particularly those unresponsive to ATO alone.
The separation of chiral enantiomers has gained increasing importance in many research fields, becoming a major research hotspot. 1,1′-Bi (2-naphthol) (BINOL) and 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (BNP) are referred to as atropisomer chiral molecules, which are essential chiral catalysts and intermediates in several reactions. In this work, BINOL and BNP atropisomers are separated and identified using trapped ion mobility spectrometry (TIMS) to monitor the different mobilities of their derivative complexes. The latter are obtained by the simple mixing of BINOL/BNP, cyclodextrin (CD), and the metal ions through noncovalent interactions. The results indicate that the enantiomer complexes of BINOL/BNP can be separated with a certain specificity, showing that R-, S-BINOL can be separated by the ternary complexes of [BINOL+γ-CD + Rb] + , [BINOL+γ-CD + Cu−H] + , and [BINOL+β-CD + Cu−H] + based on the difference in their mobility; similarly, the R-, S-BNP enantiomer can be isolated by the formed ternary complexes of [BNP+α-CD
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