Abstract
Toxicodendron vernicifluum Stokes has long been used as a food supplement and traditional herbal medicine in East Asia. We applied a new extraction method to produce Toxicodendron vernicifluum Stokes extract (TVSE), that doesn’t contain urushiol (an allergenic toxin) but dose have higher levels of some flavonoids such as fustin and fisetin. This study was conducted to investigate the anticancer effects of TVSE in an in vivo system. Fifty BALB/c mice were acclimated for one week and then injected with 4T1 murine mammary carcinoma cells in mammary fat pads. After 7 days, the mice were randomly divided into 5 groups, and orally administered with 0, 50, 100, 200 or 400 mg of TVSE/kg body weight (BW)/day for 20 days. TVSE reduced tumor volume and weight dose-dependently. The expression of Ki67 was significantly reduced and the number of TUNEL-positive apoptotic cells was significantly increased in the TVSE-treated group over 100 mg/kg BW/day. While tumor nodules were not found in the liver, but only in lungs, the number of tumor nodules was reduced in a dose-dependent manner in the TVSE treated groups compared to the control group. In breast tumors, expression of platelet endothelial cell adhesion molecule (PECAM-1) and vascular endothelial growth factor (VEGF) was reduced by TVSE treatment. TVSE treatment significantly suppressed mRNA expression in tumors of matrix metalloproteinase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-1, urokinase-type plasminogen activator (uPA), intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 while increasing plasminogen activator inhibitor (PAI)-1. These results suggest that TVSE is potentially beneficial for the suppression of breast cancer growth and its-associated lung metastasis.
Highlights
Among women, breast cancer is the most commonly diagnosed cancer (24.2% of all cancer) and the leading cause of cancer death (15.0% of deaths) worldwide [1]
To begin to define the mechanism by which Toxicodendron vernicifluum Stokes extract (TVSE) suppresses lung metastasis in breast cancer, we identified the expression of genes associated with metastasis: matrix metalloproteinase (MMP)-2, MMP-9, TIMP1, tissue inhibitor of metalloproteinase (TIMP)-2, urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor (PAI)-1, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1
This study was performed to investigate the effects of TVSE produced by a new extraction method, on the growth and lung metastasis of breast cancer in vivo
Summary
Breast cancer is the most commonly diagnosed cancer (24.2% of all cancer) and the leading cause of cancer death (15.0% of deaths) worldwide [1]. SJP, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. More than 90% of breast cancer deaths are due to metastasis-related complications [3]. Breast cancer cells can metastasize to diverse organs including lung, liver, bone, brain, etc., and once resident can proliferate into macroscopic masses, leading to death [4]. Five-year survival rates for distant metastasis breast cancer patients are less than 20% [5]
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