Histone deacetylase (HDAC) inhibitors are among the most promising targeted anticancer agents and are potent inducers of growth arrest, differentiation, and/or apoptotic cell death of transformed cells. In this study, antitumor effects of a novel sulfur‐containing hydroxamate HDAC inhibitor, H40, were observed and compared with a typical HDAC inhibitor SAHA. In biochemical HDAC assay, H40 showed a potent HDAC inhibition. It induced histone H3 hyperacetylation, correlating with inhibition of cancer cell proliferation, induction of cell differentiation and cell cycle blockage. A broad cytotoxicity was observed across cell lines from different tumor entities. The autophagy rather than apoptosis inducing activity for both H40 and SAHA was observed in prostate cancer PC‐3M cells. HDAC inhibitor‐induced p21^CIP/WAF1 expression was evident in PC‐3M and HL‐60 cell lines. The in vivo efficacy of H40 against a murine prostate carcinoma TRAMP‐C2 was compared with that of SAHA, which showed that H40 exerted a favorable antitumor action when only administered twice a week. We conclude that H40 might have clinical value in cancer chemotherapy and warrants further investigation in this regard.

In this study, quaternary berberine chloride is used as a lead compound to design and synthesize a series of berberine-12-amine derivatives to evaluate the growth inhibition activity against human cancer cell lines. Forty-two compounds of several series were obtained. The quaternary berberine-12-N,N-di-n-alkylamine chlorides showed the targeted activities with the IC₅₀ values of most active compounds being dozens of times those of the positive control. A significant structure–activity relationship (SAR) was observed. The activities of quaternary berberine-12-N,N-di-n-alkylamine chlorides are significantly stronger than those of the reduced counterparts. In the range of about 6-8 carbon atoms, the activities increase with the elongation of n-alkyl carbon chain of 12-N,N-di-n-alkylamino, and when the carbon atom numbers are more than 6-8, the activities decrease with the elongation of n-alkyl carbon chain. The activities of the tertiary amine structure are significantly higher than that of the secondary amine structure.

Eukaryotic ubiquitin and SUMO are frequently used as tags to enhance the fusion protein expression in microbial host. They increase the solubility and stability, and protect the peptides from proteolytic degradation due to their stable and highly conserved structures. Few of prokaryotic ubiquitin-like proteins was used as fusion tags except ThiS, which enhances the fusion expression, however, reduces the solubility and stability of the expressed peptides in E. coli. Hence, we investigated if MoaD, a conserved small sulfur carrier in prokaryotes with the similar structure of ubiquitin, could also be used as fusion tag in heterologous expression in E. coli.

Suberoylanilide hydroxamic acid (1), as well as other histone deacetylase (HDAC) inhibitors, are promising, targeted anticancer agents. Curcumin (2), a possible antitumor agent, exhibits a HDAC inhibiting effect but with a different mechanism, and was proposed to synergize with other drugs, including HDAC inhibitors. The present study was undertaken to evaluate the possible inhibitory effects of 1 and 2 combinations on the growth of nine human cancer cell lines. Drug combinations resulted in an antagonistic cytotoxic effect, as characterized by the Loewe additivity model, observed in all the cell lines. On the other hand, histone hyperacetylation was synergistically or at least additively induced by 1 and 2 combinations, in four cell lines tested. Despite the enhanced histone acetylation, 1 plus 2 produced a significant antagonism in the induced activation of downstream p21^CIP/WAF1 expression. Concomitantly, induced reactive oxygen species (ROS) production was antagonistically diminished in combinations especially at low concentration of 2. We conclude that 1 and 2 exert an antagonistic cytotoxicity on a variety of cancer cell lines, and suggest that mechanisms mediating their antagonism lie at levels of p21^CIP/WAF1 expression and ROS production, rather than at histone acetylation.