Apoptosis-inducing galactolipids from a cultured marine diatom, Phaeodactylum tricornutum

Abstract

Two monogalactosyl diacylglycerols, 1 and 2, were isolated from the marine diatom Phaeodactylum tricornutum, using the patented ApopScreen cell-based screen for apoptosis-inducing, potential anticancer compounds. The molecular structures of the galactolipids were determined using a combination of NMR, mass spectrometry, and chemical degradation. The bioactivities were confirmed using a specific apoptosis induction assay based on genetically engineered mammalian cell lines with differential, defined capacities for apoptosis. The galactolipids induce apoptosis in micromolar concentrations. This is the first report of apoptosis induction by galactolipids.

Figure 1

Key HMBC and selected COSY correlations for compound 1.

Figure 2

Compounds 3, 4, and 5 resulting from chemical degradation of 1.

Figure 3

Change in relative W2 and D3 cell viability by MTT assay 48 h after addition of whole cell tissue extract, fraction 3, 1, and 2 (1, 52 μM; 2, 64 μM). Staurosporine (0.1 μM), a known apoptosis inducer, and untreated cells were used as positive and negative controls, respectively. Values are an average of five wells.