The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Pladienolides, New Substances from Culture of Streptomyces platensis Mer-11107
III. In Vitro and In Vivo Antitumor Activities
YOSHIHARU MIZUITAKASHI SAKAIMASAO IWATATOSHIMITSU UENAKAKIYOSHI OKAMOTOHAJIME SHIMIZUTAKAO YAMORIKENTARO YOSHIMATSUMAKOTO ASADA
Author information
JOURNALS FREE ACCESS

2004 Volume 57 Issue 3 Pages 188-196

Details
Abstract

We have discovered seven novel 12-membered macrolides, pladienolides A to G, from Streptomyces platensis Mer-11107, with pladienolide B the most potently inhibiting hypoxia induced-VEGF expression and proliferation of the U251 cancer cell line. A growth inhibitory study using a 39-cell line drug-screening panel demonstrated that pladienolide B has strong antitumor activities in vitro. A COMPARE analysis reveals that it has a unique antitumor spectrum that sets it apart from anticancer drugs currently in clinical use. This result suggests that pladienolide B has a novel mechanism of action. A series of xenograft studies were conducted to evaluate the in vivo potency of pladienolides. Pladienolide B extensively inhibited tumor growth in xenograft models. In the most sensitive model, using BSY-1 xenografts, tumors were completely regressed by administration of pladienolide B. For the reason of their novel mechanism of action and excellent in vivo efficacy, pladienolides appear to have major potential for use in cancer treatment.

Information related to the author
© Japan Antibiotics Research Association
Previous article Next article
feedback
Top