title: Lx2-32c, a novel semi-synthetic taxane, exerts antitumor activity against prostate cancer cellsin vitroandin vivo.
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.
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
authors.forename: Guangyao
authors.initials: G
authors.lastname: Lv
authors.affiliation: Departments of Medical Oncology, Affiliated Yuhuangding Hospital, Medical College of Qingdao University, Yantai 264005, China.
authors.forename: Dengjun
authors.initials: D
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
authors.forename: Jingwen
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Xie
authors.affiliation: The Military Affiliated General Hospital of Beijing PLA, Beijing 100700, China.
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Weishuo
authors.initials: W
authors.lastname: Fang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Tian
authors.affiliation: GRU Cancer Center, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Fu
keywords: Apoptosis; Cell cycle arrest; Cephalomannine; Lx2-32c; Microtubule; Prostate cancer