Lx2-32c, a novel taxane and its antitumor activities in vitro and in vivo.
Lx2-32c, a novel taxane derivative, is a semisynthetic analogue from cephalomannine. Its antitumor activity in vivo and in vitro was investigated in this study. Lx2-32c was cytotoxic (IC50=1.7+/-1.6nM) to various human tumor cell lines after 72h incubation. In vitro it enhanced the rate of tubulin polymerization in a dose-dependent manner and induced the bundling of microtubule in BGC-823 cells with the mode similar to that of paclitaxel. As determined by flow cytometry, after either 12 or 24h exposure, Lx2-32c caused BGC-823 cells G2/M phase arrest in a time- and dose-dependent manner. Moreover, we demonstrated that Lx2-32c had significant antitumor activity on BGC-823 (human gastric carcinoma) and A549 (human non-small cell lung carcinoma) xenograft in nude mice. These data suggest that Lx2-32c is a microtubule-stabilizing agent, which has significant antitumor activity in vitro and in vivo.
Wang
Hongbo
H
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, PR China.
Li
Hongyan
H
Zuo
Minxin
M
Zhang
Yi
Y
Liu
He
H
Fang
Weishuo
W
Chen
Xiaoguang
X
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D008870:Microtubules / Q000187:drug effects; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D001952:Bridged-Ring Compounds; C532167:Lx2-32c compound; D043823:Taxoids; D014404:Tubulin; C080625:taxane; C056348:cephalomannine; D017239:Paclitaxel