Asterosaponin 1, a cytostatic compound from the starfish Culcita novaeguineae, functions by inducing apoptosis in human glioblastoma U87MG cells.
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.
Cheng
Guang
G
Department of Neurosurgery of Xijing Hospital (Neurosurgery institute of Chinese PLA), The Fourth Military Medical University, 710032, Xi'an, ShannXi, China.
Zhang
Xiang
X
Tang
Hai-Feng
HF
Zhang
Yun
Y
Zhang
Xin-Hai
XH
Cao
Wei-Dong
WD
Gao
Da-Kuan
DK
Wang
Xi-Ling
XL
Jin
Bo-quan
BQ
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D046529:Microscopy, Electron, Transmission; D011083:Polycyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D013215:Starfish / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000187:drug effects
D000970:Antineoplastic Agents; D011083:Polycyclic Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; C515773:asterosaponin 1; D051028:bcl-2-Associated X Protein