ABSTRACT. Breast cancer is a common cancer in women, with a highly variable course, from inoffensive to lethal. To find a more effective strategy for its treatment, sodium valproate has been tested as an anti-cancer drug; it is the only clinically available histone deacetylase inhibitor. However, data about the effects of sodium valproate on breast cancer are insufficient in both animals and humans; studies have yielded conflicting conclusions. In particular, little is known about the association between expression of the metastasis suppressor Nm23H1 gene and breast cancer. We hypothesized that sodium valproate regulates NM23H1 expression, and affects migration and/or invasion. We found that sodium valproate at concentrations of 0.8-3.2 mM inhibits migration and modulates Nm23H1 gene expression in a concentration-dependent manner. Confluent MDA-MB-231 cells were scratched by a micropipette tip after VPA treatment for 24 h; 24 h later, the scratch was almostly closed in the 0 mM VPA-treated cells, while the 3.2 mM VPA-treated cells migrated the slowest. The cell migration ratio exposed to 0.8, 1.6 and 3.2 mM VPA was about 66.67, 30.67 and 26.67% (P < 0.05). We also found evidence that sodium valproate upregulates NM23H1 expression, which is a clue to its anti-cancer mode of action. The NM23H1 gene expression was relative fold increased determined by Western blotting at 3.2 mM VPA. Collectively, these observations indicate that sodium valproate has potential for use in breast cancer treatment.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is a key enzyme in photosynthesis and photorespiration. The inactivation and subsequent conformational changes and dissociation of rice Rubisco by SDS have been studied. At low SDS concentrations (0.4 mM), Rubisco completely lost its carboxylase activity and most of its sulfhydryl groups became exposed. Dissociation of small subunits and significant conformational changes occurred at higher SDS concentrations. Increasing SDS concentrations caused only slight changes in CD spectrum, indicating no significant effect of SDS on the secondary structure of the enzyme. The results prove that the active site of Rubisco is more fragile to denaturants than the protein as a whole. The results also suggest that small subunits are more liable to SDS denaturation and thus dissociate first, while the more hydrophobic large subunits remain complexed. The naturally existing hydrophobic surface of Rubisco may be an important factor in the interaction of Rubisco with other macromolecules.