LAA triggers G2 /M phase cell cycle arrest via up-regulating p21expression as well as down-regulating cdk-1cyclinA singling pathway, and induces apoptotic cell death through inhibiting PI3K-Akt survival pathway in human lung adenocarcinoma A549 cells. While LAA has no significant cytotoxic effect toward normal human embryonic lung fibroblast HELF cells, and moreover, LAA could amplify the antineoplastic effects of cisplatin toward A549 cells. Lastly LAA also bears anti-cancer and apoptosis-inducing effects in vivo, and it could decrease the volume and weight of subcutaneous tumor mass obviously as well as expand lifespan of mice. These findings may provide a new perspective for elucidating the complicated molecular mechanisms of LAA-induced cancer cell growth-inhibition and death, providing a new opportunity of LAA as a potential candidate anti-neoplastic drug for future cancer therapeutics.

Lysine‐specific histone demethylase 1 (LSD1) is an attractive target for malignancies therapy. Nevertheless, its role in hepatocellular carcinoma (HCC) progression and the potential of its inhibitor in HCC therapy remains unclear. Here, we show that LSD1 overexpression in human HCC tissues is associated with HCC progression and poor patient survival. ZY0511, a highly selective and potent inhibitor of LSD1, suppressed human HCC cell proliferation in vitro and tumor growth in cell‐derived and patient‐derived HCC xenograft models in vivo. Mechanistically, ZY0511 induced mRNA expression of growth arrest and DNA damage‐inducible gene 45beta (GADD45B) by inducing histone H3 at lysine 4 (H3K4) methylation at the promoter of GADD45B, a novel target gene of LSD1. In human HCC tissues, LSD1 level was correlated with a decreased level of GADD45B, which was associated with HCC progression and predicted poor patient survival. Moreover, co‐administration of ZY0511 and DTP3, which specifically enhanced the pro‐apoptotic effect of GADD45B, effectively inhibited HCC cell proliferation both in vitro and in vivo. Collectively, our study revealed the potential value of LSD1 as a promising target of HCC therapy. ZY0511 is a promising candidate for HCC therapy through upregulating GADD45B, thereby providing a novel combinatorial strategy for treating HCC.