Toxicodendron vernicifluum Stokes extract inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice

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.

Recent Advances in Anti-Metastatic Approaches of Herbal Medicines in 5 Major Cancers: From Traditional Medicine to Modern Drug Discovery

“…Lee et al elucidated that Toxicodendron vernicifluum stokes extract (TVSE) suppressed not only the growth of solid tumors in breast itself but also the metastasis to lung in 4T1-injected mice. While decrease in Ki67 implied the inhibition of proliferation, transcriptional alternation of several genes such as MMP-2, TIMP-1, uPA, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and plasminogen activator inhibitor 1 (PAI-1) played key roles in suppressing metastasis [ 122 ]. Yue et al invented an innovative herbal formula for reducing tumor growth and extending the life span of breast cancer model.…”

Fustin, a Flavanonol, Synergically Potentiates the Anticancer Effect of Green Tea Catechin Epigallocatechin-3-O-Gallate with Activation of the eNOS/cGMP Axis

“…A previous study has suggested that this extract, containing 29% fustin without urushiol (a toxic compound in T. vernicifluum), shows modest anticancer effects on lung metastasis of 4T1 murine mammary carcinoma in an in vivo mouse model. 34 However, the efficacy of this extract is markedly limited (200 mg/kg administration induced 10% suppression of tumor volume), and its underlying mechanisms remain poorly understood.…”

Recent advances in the biosynthesis, structure–activity relationships, formulations, pharmacology, and clinical trials of fisetin

“…In MCF‐7 cells, fisetin inhibited PKCα/ROS/ERK1/2, p38 MAPK, and nuclear factor‐κB (NF‐κB) signaling, which has led to the downregulation of MMP‐9 expression (Noh et al, 2015). In addition, in vivo study showed that fisetin could significantly diminish the growth of primary breast tumor concurrent with decreased lung metastasis incidence (Lee et al, 2020).…”