Malignant
glioblastoma is one of the most common malignant
tumors in the neurological system.
Asterosaponin 1, a new
cytostatic agent from the starfish Culcita novaeguineae appear to exhibit various
biological activities, including antitumor effect, but the function and mechanism of this new agent on
glioblastoma cells has not previously been determined. In the present study, we investigated the proliferation change of human
glioblastoma U87MG cells exposed to different concentrations (2.5-20.0 microg/ml) of
asterosaponin 1 for a certain time. The results showed that
asterosaponin 1 significantly suppressed U87MG cell proliferation in a time- and dose-dependent manner (IC50 =4.3 microg/ml). Flow cytometric analysis of
DNA in U87MG cells showed that
asterosaponin 1 induces the prominent appearance of a sub-G1 peak in the cell cycle suggestive of apoptosis identical with the result of
annexin V/PI assay. Furthermore, U87MG cells treatment with
asterosaponin 1 resulted in nuclear condensation with apoptotic bodies observed by both fluorescence and electron microscopy.
Agarose gel electrophoresis of
DNA from asterosaponin 1-treated cells revealed a typical "ladder" consistent with apoptotic DNA fragmentation. Western-blot staining showed
asterosaponin 1 decreased the expression of Bcl-2
protein and increased the expression of
Bax protein. The novel findings suggest that the
cytostatic actions of
asterosaponin 1 toward U87MG cells result from the induction of cell apoptosis. Overall, our data demonstrate that
asterosaponin 1 is fully equipped for an efficient apoptotic killing of
glioblastoma cells and suggest that this mechanism may play a critical role in anti-
tumor chemotherapy.