The effect of Baicalein against lung cancer depends on GADD 45 a down-regulation

Lung cancer is one of the most universal cancers in the world. Although baicalein has been used as an anticancer reagent in lung cancer cell, the precise molecular mechanism still remains unclear. In present study, we provide the mechanistic link between baicalein and its anti-lung cancer activity. Primarily, baicalein inhibits the cell proliferation and induces cell cycle arrest, which is accompanied by the down-regulated expression of CDK4, Ki67 and PCNA. Using RNA-seq, we find that baicalein regulates the expression of nineteen genes in A549 cell, in which GADD45a (growth arrest and DNA-damage-inducible protein 45 alpha) presents a relatively lower expression. The GADD45a expression reduced by baicalein is repeatedly identified by western blotting and RT-PCR analysis, revealing that GADD45a may be a central downstream target of baicalein. Consistently, we demonstrate subsequently that over expression of GADD45a reverses the anticancer effect of baicalein on A549 cell, revealing the negative relationship between expression of GADD45a and anticancer action of baicalein. Collectively, we suggest that cell cycle arrest and lower cell proliferation induced by baicalein depend largely on down-regulated expression of GADD45a, and GADD45a is a potential biomarker for modulation or therapeutic intervention of lung cancer.

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