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

Guangyao Lv, Dengjun Sun, Jingwen Zhang, Xiaoxia Xie, Xiaoqiong Wu, Weishuo Fang, Jingwei Tian, Chunhong Yan, Hongbo Wang, Fenghua Fu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)52-58
Number of pages7
JournalActa Pharmaceutica Sinica B
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2017

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Prostatic Neoplasms
Tubulin
Cytotoxins
docetaxel
Cell Line
Cell Cycle Resting Phase
Poly(ADP-ribose) Polymerases
G2 Phase
G1 Phase
Heterografts
Nude Mice
Cell Division
Antineoplastic Agents
In Vitro Techniques
taxane
Neoplasms
Cell Cycle
Flow Cytometry
Western Blotting
Apoptosis

Keywords

  • Apoptosis
  • Cell cycle arrest
  • Cephalomannine
  • Lx2-32c
  • Microtubule
  • Prostate cancer

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cells in vitro and in vivo. / Lv, Guangyao; Sun, Dengjun; Zhang, Jingwen; Xie, Xiaoxia; Wu, Xiaoqiong; Fang, Weishuo; Tian, Jingwei; Yan, Chunhong; Wang, Hongbo; Fu, Fenghua.

In: Acta Pharmaceutica Sinica B, Vol. 7, No. 1, 01.01.2017, p. 52-58.

Research output: Contribution to journalArticle

Lv, Guangyao ; Sun, Dengjun ; Zhang, Jingwen ; Xie, Xiaoxia ; Wu, Xiaoqiong ; Fang, Weishuo ; Tian, Jingwei ; Yan, Chunhong ; Wang, Hongbo ; Fu, Fenghua. / Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cells in vitro and in vivo. In: Acta Pharmaceutica Sinica B. 2017 ; Vol. 7, No. 1. pp. 52-58.
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