PMID- 22261315
OWN - NLM
STAT- MEDLINE
DCOM- 20120906
LR  - 20120508
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 76
IP  - 3
DP  - 2012 Jun
TI  - Inhibitory effect of riccardin D on growth of human non-small cell lung cancer: 
      in vitro and in vivo studies.
PG  - 300-8
LID - 10.1016/j.lungcan.2011.12.013 [doi]
AB  - Riccardin D is a macrocyclic bisbibenzyl compound extracted from liverwort plant 
      Dumortiera hirsuta. Our previous study showed that riccardin D induced apoptosis 
      of human leukemia cells by targeting DNA topoisomerase II (topo II). Riccardin D 
      has been considered as a novel DNA topo II inhibitor and potential 
      chemotherapeutic agent for treatment of cancers. In this study, we evaluated the 
      inhibitory effects of riccardin D on growth of human non-small cell lung cancer 
      (NSCLC) both in vitro and in vivo. Riccardin D effectively inhibited the 
      proliferation of NSCLC cells as estimated by the MTT assay. Further examination 
      showed that the ability of invasion and migration of NSCLC cells was suppressed 
      on exposure to riccardin D as estimated by the assays of scratch and transwell 
      chamber. The anticancer activity of riccardin D was verified in mice bearing 
      human NSCLC H460 xenografts. Riccardin D injection produced a 44.5% inhibition of 
      cancer growth without apparent signs of toxicity to animals. Further, riccardin D 
      induced apoptosis of NSCLC cells as evidenced by the increases of cells with 
      externalization of phosphatidylserine and terminal deoxynucleotidyl transferase 
      dUTP nick-end labeling (TUNEL)-positive in H460 xenografts. The analysis of 
      apoptotic proteins showed that riccardin D activated the caspases cascade 
      signaling pathway as demonstrated by the increases of cleaved caspase-3 and 
      cleaved PARP in NSCLC cells in vitro and in H460 xenografts in mice. The pBR322 
      DNA relaxation assay indicated that riccardin D inhibited the activity of DNA 
      topo II in H460 and A549 cells, suggesting the mechanism of riccardin D in 
      induction of NSCLC apoptosis. In addition, we studied the activity and expression 
      of matrix metalloproteinases (MMPs) in NSCLC cells. The activities of MMP-2 and 
      MMP-9 in supernatants of NSCLC cells were suppressed on exposure to riccardin D 
      as estimated by gelatin zymography assay. The inhibitory effects of riccardin D 
      on expressions of MMP-2 and MMP-9 were verified in H460 xenografts in mice and 
      the decreases of vascular endothelial growth factor (VEGF) and Erk1/2 might 
      associate with the inhibition of MMPs and NSCLC growth. Together, our results 
      suggest that riccardin D has a high inhibitory effect on human NSCLC growth 
      through induction of apoptosis.
CI  - Copyright (c) 2011 Elsevier Ireland Ltd. All rights reserved.
FAU - Xue, Xia
AU  - Xue X
AD  - Department of Pharmacology, School of Pharmaceutical Sciences, Shandong 
      University, Jinan, Shandong 250012, China.
FAU - Sun, De-Fu
AU  - Sun DF
FAU - Sun, Cui-Cui
AU  - Sun CC
FAU - Liu, Hui-Ping
AU  - Liu HP
FAU - Yue, Bin
AU  - Yue B
FAU - Zhao, Cui-Rong
AU  - Zhao CR
FAU - Lou, Hong-Xiang
AU  - Lou HX
FAU - Qu, Xian-Jun
AU  - Qu XJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120117
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Phenyl Ethers)
RN  - 0 (Stilbenes)
RN  - 0 (Topoisomerase II Inhibitors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (riccardin D)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/chemistry/*pharmacology
MH  - Apoptosis/drug effects
MH  - Carcinoma, Non-Small-Cell Lung/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - DNA Topoisomerases, Type II/metabolism
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*metabolism
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase 3/metabolism
MH  - Phenyl Ethers/chemistry/*pharmacology
MH  - Stilbenes/chemistry/*pharmacology
MH  - Topoisomerase II Inhibitors/chemistry/pharmacology
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Xenograft Model Antitumor Assays
EDAT- 2012/01/21 06:00
MHDA- 2012/09/07 06:00
CRDT- 2012/01/21 06:00
PHST- 2011/01/06 00:00 [received]
PHST- 2011/12/20 00:00 [revised]
PHST- 2011/12/26 00:00 [accepted]
PHST- 2012/01/21 06:00 [entrez]
PHST- 2012/01/21 06:00 [pubmed]
PHST- 2012/09/07 06:00 [medline]
AID - S0169-5002(11)00677-5 [pii]
AID - 10.1016/j.lungcan.2011.12.013 [doi]
PST - ppublish
SO  - Lung Cancer. 2012 Jun;76(3):300-8. doi: 10.1016/j.lungcan.2011.12.013. Epub 2012 
      Jan 17.