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

Tubulin has been shown to be an effective target for the development of cytotoxic agents against prostate cancer. Previously, we reported that Lx2-32 c is an anti-tubulin agent with high binding affinity to tubulin. In this study, we investigated the potential of Lx2-32 c to act as an effective cytotoxic agent in the treatment of prostate cancer. MTT assays showed that Lx2-32 c 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 Lx2-32 c 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 Lx2-32 c was shown by Western blotting assay. Xenograft implants of LNCa P and PC3-derived tumors in nude mice showed that Lx2-32 c treatment significant inhibited tumor growth with effects equivalent to those of docetaxel. These findings demonstrate the potential of Lx2-32 c as a candidate antitumor agent for the treatment of prostate cancer.