High antitumor activity of pladienolide B and its derivative in gastric cancer.
Bottom Line: In the xenograft tumors after treatment with pladienolide B derivative, immature mRNA were detected and apoptotic cells were observed.When the expressions of cell-cycle proteins p16 and cyclin E in biopsied gastric cancer specimens were examined using immunohisctochemistry, positivities for p16 and cyclin E were significantly and marginally higher, respectively, in the low-IC50 group compared with the high-IC50 group, suggesting the possibility that they might be useful as predictive biomarkers for pladienolide B.In conclusion, pladienolide B was very active against gastric cancer via a mechanism involving splicing impairment and apoptosis induction.
Affiliation: Department of Gastroenterology and Oncology, Institutes of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.Show MeSH
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Mentions: Pladienolide B was purified as described previously.9 The pladienolide B derivative, (3R,6R,7S,8E,10 S,11S,12E,14E,16R,18R,19R,20R,21S)-7-((4-cyclo-heptylpiperazin-1-yl)carbonyl)oxy-3,6,16,21-tetrahydroxy-6,10,12,16,20-penta-methyl-18,19-epoxytrichosa-8,12,14-trien-11-olide (compound 7), was also synthesized as reported previously (Fig. 1).9
Affiliation: Department of Gastroenterology and Oncology, Institutes of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.