Abstract
Tyroservatide (YSV) is an active, low-molecular weight polypeptide shown to have antitumor effects on experimental hepatocarcinoma and lung carcinoma. The focus of our study was to observe the effects of YSV on several human lung carcinoma cell lines and explore its antitumor mechanism via its effect on histone acetylation. Our results showed that YSV significantly inhibited the proliferation of human lung carcinoma A549, NCIH460, NCIH292 and NCIH1299 cells, induced G(0) /G(1) cell cycle arrest and increased protein and mRNA levels of p21 and p27. Moreover, YSV treatment significantly inhibited histone deacetylase (HDAC) activity and resulted in the accumulation of acetylated histones H3 and H4 in total cellular chromatin and p21 gene-associated chromatin regions. Together these data suggest that the antitumor effects of YSV might be mediated by its inhibition of HDAC activity, selectively upregulating the expression of p21 by increasing the acetylation of histones associated with p21 gene regions, resulting in an induction of G₀/G₁ cell cycle arrest and inhibition of the proliferation of tumor cells. Our findings demonstrate that YSV may exhibit potent therapeutical effects on lung carcinoma.
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