PMID- 23370361
OWN - NLM
STAT- MEDLINE
DCOM- 20130805
LR  - 20211203
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 36
IP  - 2
DP  - 2013
TI  - Anticancer activity of pristimerin in epidermal growth factor receptor 2-positive 
      SKBR3 human breast cancer cells.
PG  - 316-25
AB  - Pristimerin is a naturally occurring triterpenoid that causes cytotoxicity in 
      several cancer cell lines. However, the mechanism of action for the cytotoxic 
      effect of pristimerin has not been unexplored. The purpose of this study was to 
      investigate the effect of pristimerin on cytotoxicity using the epidermal growth 
      factor receptor 2 (HER2)-positive SKBR3 human breast cancer cell line. 
      Pristimerin inhibited proliferation in dose- and time-dependent manners in cells. 
      We found it to be effective for suppressing HER2 protein and mRNA expression. 
      Fatty acid synthase (FASN) expression and FASN activity were downregulated by 
      pristimerin. Adding of exogenous palmitate, the end product of de novo fatty acid 
      synthesis, reduced the proliferation activity of pristimerin. The changes in HER2 
      and FASN expression induced by pristimerin altered the levels of Akt and 
      mitogen-activated protein kinase (MAPK) phosphorylation (Erk1/2, p38, and c-Jun 
      N-terminal kinase (JNK)). Pristimerin lowered the levels of phosphorylated 
      mammalian target of rapamycin (mTOR) and its downstream targets such as 
      phosphoprotein 70 ribosomal protein S6 kinase and 4E binding protein1. 
      Pristimerin inhibited migration and invasion of cells, and co-treatment with the 
      mTOR inhibitor rapamycin additionally suppressed these activities. 
      Pristimerin-induced apoptosis was evaluated using Western blotting for caspase-3, 
      -8, -9, and poly (ADP-ribose) polymerase expression and flow cytometric analysis 
      for propidium iodide labeling. These results suggest that pristimerin is a novel 
      HER2-downregulated compound that is able to decrease fatty acid synthase and 
      modulate the Akt, MAPK, and mTOR signaling pathways to influence metastasis and 
      apoptosis. Pristimerin may be further evaluated as a chemotherapeutic agent for 
      HER2-positive breast cancers.
FAU - Lee, Jin Sun
AU  - Lee JS
AD  - Department of Surgery, Chungnam National University Hospital, Daejeon 301-721, 
      Korea.
FAU - Yoon, In Sang
AU  - Yoon IS
FAU - Lee, Myung Sun
AU  - Lee MS
FAU - Cha, Eun Young
AU  - Cha EY
FAU - Thuong, Phuong Thien
AU  - Thuong PT
FAU - Diep, Trinh Thi
AU  - Diep TT
FAU - Kim, Je Ryong
AU  - Kim JR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Pentacyclic Triterpenes)
RN  - 0 (Plant Extracts)
RN  - 0 (RNA, Messenger)
RN  - 0 (Triterpenes)
RN  - EC 2.3.1.85 (FASN protein, human)
RN  - EC 2.3.1.85 (Fatty Acid Synthase, Type I)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspases)
RN  - L8GG98663L (celastrol)
SB  - IM
MH  - Antineoplastic Agents, Phytogenic/isolation & purification/*pharmacology
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*drug therapy/metabolism
MH  - Caspases/metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Fatty Acid Synthase, Type I/antagonists & inhibitors
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Pentacyclic Triterpenes
MH  - Plant Extracts
MH  - Plant Roots
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - RNA, Messenger/metabolism
MH  - Receptor, ErbB-2/genetics/*metabolism
MH  - Salacia
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
MH  - Triterpenes/isolation & purification/*pharmacology
MH  - Wound Healing
EDAT- 2013/02/02 06:00
MHDA- 2013/08/06 06:00
CRDT- 2013/02/02 06:00
PHST- 2013/02/02 06:00 [entrez]
PHST- 2013/02/02 06:00 [pubmed]
PHST- 2013/08/06 06:00 [medline]
AID - DN/JST.JSTAGE/bpb/b12-00685 [pii]
AID - 10.1248/bpb.b12-00685 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2013;36(2):316-25. doi: 10.1248/bpb.b12-00685.