Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cellsand.
10.1016/j.apsb.2016.06.005
- Author:
Guangyao LV
1
;
Dengjun SUN
2
;
Jingwen ZHANG
1
;
Xiaoxia XIE
1
;
Xiaoqiong WU
3
;
Weishuo FANG
4
;
Jingwei TIAN
1
;
Chunhong YAN
5
;
Hongbo WANG
1
;
Fenghua FU
1
Author Information
1. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
2. Departments of Medical Oncology, Affiliated Yuhuangding Hospital, Medical College of Qingdao University, Yantai 264005, China.
3. The Military Affiliated General Hospital of Beijing PLA, Beijing 100700, China.
4. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
5. GRU Cancer Center, Georgia Regents University, Augusta, GA 30912, USA.
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Cell cycle arrest;
Cephalomannine;
Lx2-32c;
Microtubule;
Prostate cancer
- From:
Acta Pharmaceutica Sinica B
2017;7(1):52-58
- CountryChina
- Language:English
-
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.
