Investigation of the component of Lycopodium serratum extract that inhibits proliferation and mediates apoptosis of human HL-60 leukemia cells

In this study, we investigate a plant commonly used in herbal medicines, Lycopodium serratum , which is believed to have anti-cancer properties. An alcoholic extract of L. serratum (LSE) was investigated for its ability to induce apoptosis in cultured human promyelocytic leukemia HL-60 cells. Treatment of HL-60 cells with various concentrations of LSE (6–100 μg/mL) resulted in a sequence of events characteristic of apoptosis, including loss of cell viability, morphological changes, and increased sub-G 1 DNA content. Serratenediol (SE), a known biologically active agent, was isolated from MC fraction of LSE and was able to demonstrate significant and dose-dependent growth inhibitory effects on HL-60 cells. Similar to the effects observed with the crude LSE, the SE-related effects included the formation of apoptotic bodies and fragmented DNA, as well as the accumulation of DNA in the sub-G 1 phase of the cell cycle. Analysis of the mechanism of these events indicated that SE treated cells had an increased ratio of Bax/Bcl-xL, released the cytochrome c , activated caspase-9, -3, and cleaved poly-ADP-ribose polymerase (PARP); these observations are hallmarks of apoptotic events. Thus, the results suggest that SE can induce apoptosis via regulating the ratio of Bax/Bcl-xL in HL-60 cell lines.