Cytotoxic effects of escin on human castration-resistant prostate cancer cells through the induction of apoptosis and G2/M cell cycle arrest.

Abstract

OBJECTIVE:

To evaluate the in vitro and in vivo effects of escin on human castration-resistant prostate cancer (CRPC) cells, PC-3 and DU-145.

MATERIALS AND METHODS:

The inhibition of cell proliferation and its mechanism were assessed through a cytotoxicity assay, flow cytometry, and Western blot. The in vivo efficacy of escin in CRPC cells was assessed using a xenograft tumor model subcutaneously established in BALB/c nude mice.

RESULTS:

The treatment with escin significantly reduced cell viability of CRPC cells in a dose- and time-dependent manner. Escin induced apoptosis in a time-dependent manner, which was accompanied by increases in pro-apoptotic (BCL-2 associated X protein, cleaved-caspase3, and cleaved-poly [adenosine diphosphate-ribose] polymerase) proteins and decreases in antiapoptotic (X-linked inhibitor of apoptosis protein, cellular inhibitor of apoptosis protein-1, cellular inhibitor of apoptosis protein-2B-cell leukemia/lymphoma-2, and B-cell lymphoma-extra large) proteins. Escin induced G2/M-phase cell cycle arrest and thus led to a significant decrease in the expression of cyclinB1 and its activating partner cyclin-dependent kinase 1, with the concomitant induction of p21. In addition, escin significantly inhibited the growth of CRPC cells in xenograft models.

CONCLUSION:

The results show that escin induced cytotoxic effects on CRPC cells through the induction of apoptosis and G2/M cell cycle arrest, indicating it may be a novel therapeutic agent for CRPC.

• Authors: Songzhe Piao, Minyong Kang, Young Ju Lee, Woo Suk Choi, Yang-Sook Chun, Cheol Kwak, Hyeon Hoe Kim
• Journal: Urology (Urology) Vol. 84 Issue 4 Pg. 982.e1-7 (Oct 2014) ISSN: 1527-9995 [Electronic] United States
• PMID: 25123426 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Escin

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• Escin (pharmacology)
• G2 Phase Cell Cycle Checkpoints (drug effects)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Prostatic Neoplasms, Castration-Resistant (pathology)