TY - JOUR
T1 - Cell cycle perturbations and apoptosis induced by isohomohalichondrin B (IHB), a natural marine compound
AU - Bergamaschi, D.
AU - Ronzoni, S.
AU - Taverna, S.
AU - Faretta, M.
AU - De Feudis, P.
AU - Faircloth, G.
AU - Jimeno, J.
AU - Erba, E.
AU - D'Incalci, M.
PY - 1999
Y1 - 1999
N2 - Isohomohalichondrin B (IHB), a novel marine compound with anti-tumoral activity, extracted from the Lissodendorix sponge, inhibits GTP binding to tubulin, preventing microtubule assembly. Cell cycle perturbations and apoptosis induced by IHB were investigated on selected human cancer cell lines by using flow cytometric and biochemical techniques. Monoparameter flow cytometric analysis showed that 1 h IHB exposure caused a delayed progression through S-phase, a dramatic block in G2M phase of the cell cycle and the appearance of tetraploid cell population in LoVo, LoVo/DX, MOLT-4 and K562 cells. At 24 h after IHB exposure, the majority of cells blocked in G2M were in prophase as assessed by morphological analysis and by the fact that they expressed high levels of cyclin A/cdc2 and cyclin B1/cdc2. At 48 h all cells were tetraploid as assessed by biparameter cyclin A/DNA and cyclin B1/DNA content analysis. Apoptotic death was detected in both leukaemic MOLT-4 and K562 cells, which express wild-type and mutated p53 respectively, when the cells were blocked in mitotic prophase. In conclusion, IHB is a novel potent anti-tumour drug that causes delayed S-phase progression, mitotic block, tetraploidy and apoptosis in cancer cell lines.
AB - Isohomohalichondrin B (IHB), a novel marine compound with anti-tumoral activity, extracted from the Lissodendorix sponge, inhibits GTP binding to tubulin, preventing microtubule assembly. Cell cycle perturbations and apoptosis induced by IHB were investigated on selected human cancer cell lines by using flow cytometric and biochemical techniques. Monoparameter flow cytometric analysis showed that 1 h IHB exposure caused a delayed progression through S-phase, a dramatic block in G2M phase of the cell cycle and the appearance of tetraploid cell population in LoVo, LoVo/DX, MOLT-4 and K562 cells. At 24 h after IHB exposure, the majority of cells blocked in G2M were in prophase as assessed by morphological analysis and by the fact that they expressed high levels of cyclin A/cdc2 and cyclin B1/cdc2. At 48 h all cells were tetraploid as assessed by biparameter cyclin A/DNA and cyclin B1/DNA content analysis. Apoptotic death was detected in both leukaemic MOLT-4 and K562 cells, which express wild-type and mutated p53 respectively, when the cells were blocked in mitotic prophase. In conclusion, IHB is a novel potent anti-tumour drug that causes delayed S-phase progression, mitotic block, tetraploidy and apoptosis in cancer cell lines.
KW - Apoptosis
KW - Isohomohalichondrin B
KW - Mitotic block
KW - Natural compound
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UR - http://www.scopus.com/inward/citedby.url?scp=0032894275&partnerID=8YFLogxK
M3 - Article
C2 - 9888468
AN - SCOPUS:0032894275
VL - 79
SP - 267
EP - 277
JO - British Journal of Cancer
JF - British Journal of Cancer
SN - 0007-0920
IS - 2
ER -