Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cells in vitro and in vivo

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• 作者：Guangyao Lv^a ; ^&dagger ; ; Dengjun Sun^b ; ^&dagger ; ; Jingwen Zhang^a ; Xiaoxia Xie^a ; Xiaoqiong Wu^d ; Weishuo Fang^c ; Jingwei Tian^a ; Chunhong Yan^e ; Hongbo Wang^a ; ^{hongbowangyt@gmail.com} ; Fenghua Fu^a ; ^{fufenghua@sohu.com}
• 关键词：Lx2-32c ; Cephalomannine ; Prostate cancer ; Microtubule ; Cell cycle arrest ; Apoptosis
• 刊名：Acta Pharmaceutica Sinica B
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：7
• 期：1
• 页码：52-58
• 全文大小：1007 K
• 卷排序：7

文摘

Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32c was cytotoxic to all tested prostate cancer cell lines. The Lx2-32c-treated cells typically exhibited a rounded morphology associated with the onset of apoptosis, as evidenced by immunocytochemical staining. Human prostate cancer cell lines treated with Lx2-32c arrest in the G2/M phase of the cell cycle and the treatment is associated with an increased ratio of cells in the sub-G0/G1 phase as determined by flow cytometry. Furthermore, expression of the cleaved form of poly (ADP-ribose) polymerase in prostate cancer cell lines treated with Lx2-32c was shown by Western blotting assay. Xenograft implants of LNCaP and PC3-derived tumors in nude mice showed that Lx2-32c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32c as a candidate antitumor agent for the treatment of prostate cancer.