Influence of cucumariosides upon intracellular [Ca 2+]i and lysosomal activity of macrophages

Biological effects of the triterpene glycosides, cucumariosides A(2)-2 and A(7)-1 from the edible sea cucumber Cucumaria japonica and their aglycones were investigated using embryos of the sea urchin Strongylocentrotus nudus and the BALB/C line mouse peritoneal macrophages. Cucumariosides were highly cytotoxic in a sea urchin embryo development test with EC50 values of 0.3 and 1.98 mug/mL, respectively. The aglycone was completely lacking in cytotoxicity. In subtoxic concentrations (0.001-0.1 mug/mL), cucumarioside A(2)-2 showed more then 2-fold stimulation of lysosomal activity and induced a rapid short-term increase in cytosolic Ca2+ Content in mouse macrophages. The maximal stimulatory effect was detected after 1-2 h of cultivation of cells with this glycoside. Cucumarioside A(7)-1 demonstrated more weak effects and even slightly inhibited lysosomal activity, while the aglycone was completely ineffective. At the toxic concentration (1 mug/mL), cucumarioside A(2)-2 induced the sharp irreversable increase of intracellular Ca2+ concentration. We suggested that cucumariosides, especially A(2)-2, may act as Ca2+ agonists due to their membranolytic properties.