Pristimerin inhibits breast cancer cell migration by up- regulating regulator of G protein signaling 4 expression.

Abstract

BACKGROUND/AIM:

Pristimerin isolated from Celastrus and Maytenus spp can inhibit proteasome activity. However, whether pristimerin can modulate cancer metastasis is unknown.

METHODS:

The impacts of pristimerin on the purified and intracellular chymotrypsin proteasomal activity, the levels of regulator of G protein signaling 4 (RGS 4) expression and breast cancer cell lamellipodia formation, and the migration and invasion were determined by enzymatic, Western blot, immunofluorescent, and transwell assays, respectively.

RESULTS:

We found that pristimerin inhibited human chymotrypsin proteasomal activity in MDA-MB-231 cells in a dose-dependent manner. Pristimerin also inhibited breast cancer cell lamellipodia formation, migration, and invasion in vitro by up-regulating RGS4 expression. Thus, knockdown of RGS4 attenuated pristimerin-mediated inhibition of breast cancer cell migration and invasion. Furthermore, pristimerin inhibited growth and invasion of implanted breast tumors in mice.

CONCLUSION:

Pristmerin inhibits proteasomal activity and increases the levels of RGS4, inhibiting the migration and invasion of breast cancer cells.

• Authors: Xian-Min Mu, Wei Shi, Li-Xin Sun, Han Li, Yu-Rong Wang, Zhen-Zhou Jiang, Lu-Yong Zhang
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 13 Issue 4 Pg. 1097-104 ( 2012) ISSN: 2476-762X [Electronic] Thailand
• PMID: 22799288 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Antineoplastic Agents
• Leupeptins
• Pentacyclic Triterpenes
• Proteasome Inhibitors
• RGS Proteins
• Triterpenes
• RGS4 protein
• Chymases
• Proteasome Endopeptidase Complex
• celastrol
• benzyloxycarbonylleucyl-leucyl-leucine aldehyde

Topics

• Actins (metabolism)
• Analysis of Variance
• Animals
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (enzymology, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Chymases (drug effects, metabolism)
• Dose-Response Relationship, Drug
• Female
• Humans
• Leupeptins (pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Invasiveness
• Pentacyclic Triterpenes
• Proteasome Endopeptidase Complex (drug effects, metabolism)
• Proteasome Inhibitors (pharmacology)
• RGS Proteins (drug effects, genetics, metabolism)
• RNA Interference
• Random Allocation
• Triterpenes (pharmacology)
• Tumor Burden (drug effects)
• Up-Regulation