PMID- 29093327
OWN - NLM
STAT- MEDLINE
DCOM- 20180806
LR  - 20180806
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 41
IP  - 1
DP  - 2018 Jan 1
TI  - Chelerythrine Inhibits Human Hepatocellular Carcinoma Metastasis in Vitro.
PG  - 36-46
LID - 10.1248/bpb.b17-00451 [doi]
AB  - Chelerythrine (CHE) is a type of benzophenanthridine alkaloid found in many herbs 
      and is also the main alkaloid constituent of Toddalia asiatica (L.) LAM. It has 
      been proven to have various activities including antitumor, antifungal, 
      anti-inflammatory and anti-parasitic effects. We have previously demonstrated 
      that CHE can inhibit proliferation and promote apoptosis in human hepatocellular 
      carcinoma (HCC) cells. However, the effect of CHE on the metastasis of HCC and 
      its related molecular mechanisms have yet to be validated. In this study, we 
      investigated the effects of CHE on the migration and invasion of the HCC cell 
      line Hep3B. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 
      wounding healing, transwell migration and invasion assays and cytoskeleton 
      staining demonstrated that CHE could inhibit the migration and invasion of Hep3B 
      cells in a dose-dependent manner with change of cell structure. RNA interference 
      studies made a knockdown of matrix metalloproteinase (MMP)-2/9 respectively in 
      Hep3B cells. And the results of wounding healing and transwell invasion assay 
      with the treatment of small interfering RNA (siRNA) investigated that MMP-2/9 are 
      positively associated with Hep3B cell metastasis. The results of enzyme-linked 
      immunosorbent assay (ELISA), Western blotting and quantitative RT-PCR showed that 
      CHE suppressed the expression of MMP-2/9 at both mRNA and protein levels. CHE 
      also exhibited an inhibitory effect on the phosphorylation of Focal adhesion 
      kinase (FAK), phosphatidylinositol 3-kinase (PI3K), Akt, mammalian target of 
      rapamycin (mTOR), c-Jun N-terminal kinase (JNK), extracellular signal-regulated 
      kinases (ERK) and p38. In summary, on Hep3B cells, CHE could change the cell 
      cytoskeletal structures through reducing the expression of p-FAK and inhibit the 
      metastasis of Hep3B cells by downregulating the expression of MMP-2/9 mainly 
      through PI3K/Akt/mTOR signaling pathway.
FAU - Zhu, Yuanzhang
AU  - Zhu Y
AD  - Laboratory of Formula, School of Pharmacy, Shanghai University of Traditional 
      Chinese Medicine.
FAU - Pan, Yingyi
AU  - Pan Y
AD  - Department of Traditional Chinese Medicine, School of Pharmacy, Shanghai 
      University of Traditional Chinese Medicine.
FAU - Zhang, Guibiao
AU  - Zhang G
AD  - Department of Traditional Chinese Medicine, School of Pharmacy, Shanghai 
      University of Traditional Chinese Medicine.
FAU - Wu, Yingchun
AU  - Wu Y
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine.
FAU - Zhong, Weicai
AU  - Zhong W
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine.
FAU - Chu, Chunxiao
AU  - Chu C
AD  - School of Pharmacy, Shanghai University of Traditional Chinese Medicine.
FAU - Qian, Yun
AU  - Qian Y
AD  - Laboratory of Formula, School of Pharmacy, Shanghai University of Traditional 
      Chinese Medicine.
FAU - Zhu, Guofu
AU  - Zhu G
AD  - Department of Traditional Chinese Medicine, School of Pharmacy, Shanghai 
      University of Traditional Chinese Medicine.
LA  - eng
PT  - Journal Article
DEP - 20171031
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzophenanthridines)
RN  - E3B045W6X0 (chelerythrine)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Benzophenanthridines/*pharmacology
MH  - Carcinoma, Hepatocellular/metabolism/*pathology
MH  - Cell Line, Tumor
MH  - Cell Movement/*drug effects
MH  - Cell Survival/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Hep G2 Cells
MH  - Humans
MH  - Liver Neoplasms/metabolism/*pathology
MH  - Neoplasm Invasiveness
MH  - Neoplasm Metastasis
OTO - NOTNLM
OT  - Chelerythrine
OT  - hepatocellular carcinoma
OT  - metastasis
EDAT- 2017/11/03 06:00
MHDA- 2018/08/07 06:00
CRDT- 2017/11/03 06:00
PHST- 2017/11/03 06:00 [pubmed]
PHST- 2018/08/07 06:00 [medline]
PHST- 2017/11/03 06:00 [entrez]
AID - 10.1248/bpb.b17-00451 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2018 Jan 1;41(1):36-46. doi: 10.1248/bpb.b17-00451. Epub 2017 
      Oct 31.