Inhibition Effects of Lamellarin D on Human Leukemia K562 Cell Proliferation and Underlying Mechanisms

Lamellarin D (LamD) is a marine alkaloid with a pronounced cytotoxicity against a large panel of cancer cells,affecting cell growth and inducing apoptosis. However, the molecular mechanisms of action of this compoundare poorly understood. In this study, the anticancer efficacy of LamD was investigated in human leukemia K562cells. The results showed suppressed cell proliferation and induction of G0/G1-phase arrest,while expression ofCDK1, and activity of smad3 and smad5 were reduced, but that of p27, p53 and STGC3 was increased. LamDinduced cell apoptosis through activation of caspases-8/-3, inhibition of survivin and Bcl-2, suggesting that thiscompound may also act through a caspase-independent pathway. Moreover, LamD inhibited the secretion ofTGF-β, IL-1β, IL-6, IL-8 and other inflammatory cytokines and the transcriptional activity of transcriptionfactor NF-κB in human leukemia K562 cells.Taken together, our results suggest that LamD-mediated inhibitionof leukemia cell proliferation may be related to the induction of apoptosis and the regulation of cell cycle, tumorrelatedgene expression and cytokine expression, which may provide a new way of thinking for the treatmentleukemia.