Breviscapine (BVP) inhibits prostate cancer progression through damaging DNA by minichromosome maintenance protein-7 (MCM-7) modulation.

Abstract

Naturally occurring compounds are reported as effective candidates for prevention and treatment of various cancers. Breviscapine (BVP) is a mixture of flavonoid glycosides, derived from the Chinese herbs. Previous researches have indicated that BVP has comprehensive pharmacological functions. However, little is known about whether BVP has preventive effects on human prostate cancer. Here, we attempted to explore if BVP inhibits human prostate cancer in vitro and in vivo in a comprehensive manner. We found that BVP triggered cytotoxicity in prostate cancer cell lines dose-dependently. BVP-induced DNA damage caused the cell cycle arrest and apoptosis and further induced cell death. High expression of MCM-7 was reduced in BVP-treated cancer cells and tumor tissues, and also the DNA damage response marker of γH2AX is down-regulated by BVP, associated with MCM-7 expression through regulating retinoblastoma protein (Rb) and checkpoint control proteins expression. Additionally, BVP induced apoptotic response in prostate cancer cells and tumors via activating Caspase-3 and PARP. In vivo studies indicated that BVP impeded tumor growth in xenograft animal models. In conclusion, our data indicates that breviscapine (BVP) can be further explored for its potential, which might be used in human prostate cancer therapeutics.

• Authors: Yang-Bo Guan, Dong-Rong Yang, Shao-Jun Nong, Jian Ni, Chun-Hui Hu, Jian Li, Jin Zhu, Yu-Xi Shan
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 93 Pg. 103-116 (Sep 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28628830 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Cell Cycle Proteins
• Flavonoids
• Retinoblastoma Protein
• breviscapine
• DNA
• Caspase 3
• MCM7 protein, human
• Minichromosome Maintenance Complex Component 7

Topics

• Animals
• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Cycle Checkpoints (drug effects)
• Cell Cycle Proteins (metabolism)
• Cell Line, Tumor
• DNA (metabolism)
• DNA Damage (drug effects)
• Down-Regulation (drug effects)
• Flavonoids (pharmacology)
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Minichromosome Maintenance Complex Component 7 (metabolism)
• Prostatic Neoplasms (drug therapy, metabolism)
• Retinoblastoma Protein (metabolism)