Alteration in histone acetylation have been implicated as a hallmarker of carcinogenesis. Histone deacetylase inhibitors, such as (S)-HDAC-42, suberoylanilide hydroxamic acid (SAHA), have shown to restore histone acetylation and allow gene transcription. The histone acetylation induced by HDAC inhibitors can reactivate the expressions of silenced gene in cancer cells, such as Bcl-2 or p53. However, in addition to the mechanisms of cell growth, differentiation, and apoptosis mediated by (S)-HDAC-42 remain unclear, besides the inhibition of histone deacetylase.
Based on studies in the literature, SAHA has been shown to induce cell death, cell cycle arrest, and apoptosis in leukemia and prostate cancer cell lines. The differential tumorigenesis between leukemia and myeloma is originated from different stages during B-cell maturation. As a result, we rationally suggest that (S)-HDAC-42 may have a similar or even better therapeutic activity in multiple myeloma.
In this study, we assessed the effects of (S)-HDAC-42 in cell growth, apoptosis and molecular signal transduction in multiple myeloma cell lines compared to SAHA. The preliminary data revealed that (S)-HDAC-42 induced the cell grow inhibition and apoptosis which are better than those of SAHA in multiple myeloma cells.
Moreover, the induction of apoptosis mediated by (S)-HDAC-42 was through mitochondria dependent pathway and down regulation of Akt and NF-κB pathways which are related to cell proliferation as well as survival pathway.
