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High antitumor activity of pladienolide B and its derivative in gastric cancer.

Sato M, Muguruma N, Nakagawa T, Okamoto K, Kimura T, Kitamura S, Yano H, Sannomiya K, Goji T, Miyamoto H, Okahisa T, Mikasa H, Wada S, Iwata M, Takayama T - Cancer Sci. (2013)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Oncology, Institutes of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.

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Structures of pladienolide B (a) and its derivative (b). To increase the stability and antitumor activity of pladienolide B, the acetyl group at the C7 position was substituted with 4-cyclo-heptylpiperazin-1-yl and a hydroxyl group was added to the C16 position.
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fig01: Structures of pladienolide B (a) and its derivative (b). To increase the stability and antitumor activity of pladienolide B, the acetyl group at the C7 position was substituted with 4-cyclo-heptylpiperazin-1-yl and a hydroxyl group was added to the C16 position.

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


High antitumor activity of pladienolide B and its derivative in gastric cancer.

Sato M, Muguruma N, Nakagawa T, Okamoto K, Kimura T, Kitamura S, Yano H, Sannomiya K, Goji T, Miyamoto H, Okahisa T, Mikasa H, Wada S, Iwata M, Takayama T - Cancer Sci. (2013)

Structures of pladienolide B (a) and its derivative (b). To increase the stability and antitumor activity of pladienolide B, the acetyl group at the C7 position was substituted with 4-cyclo-heptylpiperazin-1-yl and a hydroxyl group was added to the C16 position.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317874&req=5

fig01: Structures of pladienolide B (a) and its derivative (b). To increase the stability and antitumor activity of pladienolide B, the acetyl group at the C7 position was substituted with 4-cyclo-heptylpiperazin-1-yl and a hydroxyl group was added to the C16 position.
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

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Oncology, Institutes of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.

Show MeSH
Related in: MedlinePlus