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


CONCLUSIONS
Pristmerin inhibits proteasomal activity and increases the levels of RGS4, inhibiting the migration and invasion of breast cancer cells.
Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing, China.
Xian-Min
XM
Mu
Wei
W
Shi
Li-Xin
LX
Sun
Han
H
Li
Yu-Rong
YR
Wang
Zhen-Zhou
ZZ
Jiang
Lu-Yong
LY
Zhang
D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D053818:Chymases / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D053978:Pentacyclic Triterpenes; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology*; D020710:RGS Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011897:Random Allocation; D014315:Triterpenes / Q000494:pharmacology*; D047368:Tumor Burden / Q000187:drug effects; D015854:Up-Regulation
D000199:Actins; D000970:Antineoplastic Agents; D007976:Leupeptins; D053978:Pentacyclic Triterpenes; D061988:Proteasome Inhibitors; D020710:RGS Proteins; D014315:Triterpenes; C098799:RGS4 protein; D053818:Chymases; D046988:Proteasome Endopeptidase Complex; C050414:celastrol; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde