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Cucurbitacin B markedly inhibits growth and rapidly affects the cytoskeleton in glioblastoma multiforme
Author(s) -
Yin Dong,
Wakimoto Naoki,
Xing Hongtao,
Lu Daning,
Huynh Thien,
Wang Xiao,
Black Keith L.,
Koeffler H. Phillip
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23648
Subject(s) - clonogenic assay , cell culture , cytoskeleton , cancer research , western blot , cell growth , cell , microtubule , pseudopodia , biology , actin , microbiology and biotechnology , chemistry , medicine , biochemistry , genetics , gene
Glioblastoma Multiforme (GBM) is almost inevitably a fatal tumor of the brain with most individuals dying within 1 year of diagnosis. It is the most frequent brain tumor in adults. Dose‐response studies showed that Cucurbitacin B inhibited 50% growth (ED 50 ) of 5 human GBM cell lines in liquid culture at ∼10 −7 M. Soft‐gel assays demonstrated that nearly all of the GBM clonogenic cells were inhibited at 10 −8 M of Cucurbitacin B. FACS analysis found that the compound (10 −7 M, 24 hr) caused G2/M arrest. The GBM cells underwent profound morphologic changes within 15–30 min after exposure to Cucurbitacin B (10 −7 M), rounding up and losing their pseudopodia associated with disruption of actin and microtubules, as observed by immunoflourescence. Cucurbitacin B (10 −7 M) caused prominent multinucleation of the cells after they were pulse‐exposed (48 hr) to the drug, washed and cultured in normal medium for an additional 2 days. The drug (10 −7 M, 3–24 hr) increased levels of p‐p38, p‐JNK and p‐JUN in U87 and T98G GBM cell lines as seen by Western blot. Interestingly, alterations in cell morphology caused by Cucurbitacin B (10 −7 M) were blocked by the JNK inhibitor SP600125. In summary, Cucurbitacin B has a prominent anti‐proliferative activity on GBM cells; and at least in part, the mode of action is by affecting the cytoskeleton, as well as, the JNK pathway. Clinical trails of this drug should be pursued in GBM. © 2008 Wiley‐Liss, Inc.