PMID- 32630806
OWN - NLM
STAT- MEDLINE
DCOM- 20210216
LR  - 20221207
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 13
DP  - 2020 Jul 2
TI  - Identification of Matrine as a Novel Regulator of the CXCR4 Signaling Axis in 
      Tumor Cells.
LID - 10.3390/ijms21134731 [doi]
LID - 4731
AB  - Matrine, a quinolizidine alkaloid, is commonly employed for treating various 
      viral and inflammatory disorders. Here, we have evaluated matrine for its 
      activity on C-X-C chemokine receptor type 4 (CXCR4) and matrix metalloproteinases 
      (MMP-9/2) expression, and its potential to affect tumor metastasis and invasion. 
      The effects of matrine on CXCR4, MMP-9/2, and nuclear factor kappaB (NF-kappaB) 
      activation in lung (A549), prostate (DU145), and pancreas (MIA PaCa-2) cells were 
      investigated by diverse techniques. The expression level of CXCR4 and MMP-9/2 was 
      analyzed by western blot analysis and reverse transcription polymerase chain 
      reaction. NF-kappaB activation was also evaluated by western blot analysis, 
      electrophoretic mobility shift assay as well as immunocytochemical experiments. 
      Furthermore, we monitored cell invasion and metastasis activities by wound 
      healing and Boyden chamber assays. We noted that matrine induced a 
      down-regulation of CXCR4 and MMP-9/2 at both protein and mRNA levels. In 
      addition, matrine negatively regulated human epidermal growth factor receptor 2 
      (HER2) and C-X-C Motif Chemokine Ligand 12 (CXCL12)-induced CXCR4 expression. 
      Moreover, NF-kappaB suppression by matrine led to inhibition of metastatic potential 
      of tumor cells. Our results suggest that matrine can block the cancer metastasis 
      through the negative regulation of CXCR4 and MMP-9/2 and consequently it can be 
      considered as a potential candidate for cancer therapy.
FAU - Jung, Young Yun
AU  - Jung YY
AD  - Department of Science in Korean Medicine, Kyung Hee University, 24 
      Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
FAU - Um, Jae-Young
AU  - Um JY
AD  - Department of Science in Korean Medicine, Kyung Hee University, 24 
      Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
FAU - Narula, Acharan S
AU  - Narula AS
AD  - Narula Research, Chapel Hill, NC 27516, USA.
FAU - Namjoshi, Ojas A
AU  - Namjoshi OA
AD  - Center for Drug Discovery, RTI International, Research Triangle Park, Durham, NC 
      27709, USA.
FAU - Blough, Bruce E
AU  - Blough BE
AD  - Center for Drug Discovery, RTI International, Research Triangle Park, Durham, NC 
      27709, USA.
FAU - Kumar, Alan Prem
AU  - Kumar AP
AUID- ORCID: 0000-0002-3754-5712
AD  - Cancer Science Institute of Singapore, National University of Singapore, 
      Singapore 117599, Singapore.
AD  - Department of Pharmacology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore 117600, Singapore.
FAU - Ahn, Kwang Seok
AU  - Ahn KS
AUID- ORCID: 0000-0002-2882-0612
AD  - Department of Science in Korean Medicine, Kyung Hee University, 24 
      Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.
LA  - eng
GR  - NRF-2018R1D1A1B07042969/National Research Foundation of Korea/
PT  - Journal Article
DEP - 20200702
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Alkaloids)
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (NF-kappa B)
RN  - 0 (Quinolizines)
RN  - 0 (Receptors, CXCR4)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - 0 (Matrines)
SB  - IM
MH  - A549 Cells
MH  - Alkaloids/*metabolism/*pharmacology
MH  - Antineoplastic Agents, Phytogenic/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Movement/genetics
MH  - Cell Proliferation/genetics
MH  - Gene Expression Regulation, Neoplastic/*drug effects/genetics
MH  - Humans
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Matrix Metalloproteinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Neoplasm Invasiveness/genetics
MH  - Neoplasms/metabolism
MH  - Quinolizines/*metabolism/*pharmacology
MH  - Receptors, CXCR4/metabolism/physiology
MH  - Signal Transduction/drug effects
MH  - Matrines
PMC - PMC7370290
OTO - NOTNLM
OT  - CXCR4
OT  - MMP-9/2
OT  - NF-kB
OT  - matrine
COIS- The authors declare no conflict of interest.
EDAT- 2020/07/08 06:00
MHDA- 2021/02/17 06:00
PMCR- 2020/07/01
CRDT- 2020/07/08 06:00
PHST- 2020/06/10 00:00 [received]
PHST- 2020/06/29 00:00 [revised]
PHST- 2020/06/30 00:00 [accepted]
PHST- 2020/07/08 06:00 [entrez]
PHST- 2020/07/08 06:00 [pubmed]
PHST- 2021/02/17 06:00 [medline]
PHST- 2020/07/01 00:00 [pmc-release]
AID - ijms21134731 [pii]
AID - ijms-21-04731 [pii]
AID - 10.3390/ijms21134731 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Jul 2;21(13):4731. doi: 10.3390/ijms21134731.