Cancer stem cells (CSCs) are a subset of cancer cells which have self-renewal ability and exist in various tumors. Inhibition of CSCs self-renewal is considered as a new method for tumor therapy. A novel semi-synthetic taxane analogue, Lx2-32c, could overcome drug resistance in various cancer cell lines. In this study, it was found that Lx2-32c inhibited the proliferation and mammosphere formation of MDA-MB-231-derived cancer stem cell-like cells (MCSCLCs) and induced apoptosis, as well as down-regulated the expression of FoxM1 and CD44 in MCSCLCs. Simultaneously, it was proved that Lx2-32c combined with thiostreption, a FoxM1 inhibitor inhibited proliferation and mammosphere formation of MCSCLCs and induced apoptosis to a more extent than Lx2-32c alone; thiostreption could also enhance the effect of Lx2-32c of reduction of the expression of FoxM1 and CD44. All of these results indicated that Lx2-32c is a novel semi-synthetic taxane analogue which inhibits the self-renewal of MCSCLCs cells and induces apoptosis involving in down-regulating FoxM1.

01 Jan 2017·Acta Pharmaceutica Sinica BQ1 · CHEMISTRY

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

Q1 · CHEMISTRY

ArticleOA

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

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.

01 Jan 2014·Journal of Pharmaceutical and Biomedical AnalysisQ3 · MEDICINE

Quantitative determination of Lx2-32c, a novel taxane derivative, in rat plasma by liquid chromatography–tandem mass spectrometry

Q3 · MEDICINE

Article

Author: Shu Yang ; Yan Li ; Feng You ; Jinping Hu

A sensitive and reliable LC-MS/MS method for the determination of Lx2-32c, a novel taxane derived from cephalomannine, has been developed and validated. Plasma samples containing Lx2-32c and paclitaxel (internal standard) were prepared based on a simple protein precipitation by the addition of two volumes of acetonitrile. The analyte and internal standard were separated on a Zorbax SB-C18 column (3.5μm, 2.1mm×100mm) with the mobile phase of acetonitrile/water containing 0.1% formic acid (v/v) with gradient elution at a flow rate of 0.2ml/min. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with atmospheric pressure chemical ionization (APCI) by multiple reactions monitoring (MRM) of the transitions at m/z 887.5→264.3 for Lx2-32c and 854.5→286.2 for IS. Linear detection responses were obtained for Lx2-32c ranging from 1 to 1000ng/ml. Inter- and intra-day precision (R.S.D.%) were all within 15% and the accuracy (R.E.%) was equal or lower than 8%. The lower limit of quantitation (LLOQ) was 1ng/ml and the average recovery was greater than 91.5%. The method was successfully applied to the pharmacokinetic study of Lx2-32c in rat plasma.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	China	Chinese Academy of Medical Sciences	08 Sep 2008
Neoplasms	Preclinical	China	Peking Union Medical College Hospital	08 Sep 2008

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