Search

Growing evidence has shown that menthol has potent anticancer activity in various human cancers. However, its effect on skin cancer remains largely unknown. In the present study, we investigated the chemopreventive potential of menthol against 7, 12-dimethylbenz[a] anthracene(DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin tumorigenesis in ICR mice. Our results showed that menthol significantly inhibited TPA-induced inflammatory responses and pro-inflammatory cytokine release. We also found that menthol treatment significantly inhibited TPA-induced lipid peroxidation (LPO), mouse UDP-glucumno-syltransferase (UGT), mouse NADH Dehydrogenase, Quinone 1 (NQO1) release. Furthermore, we found menthol treatment significantly inhibited the tumor incidence and number of tumors (P < 0.001). Interestingly, we observed that menthol treatment significantly inhibited TPA-induced altered activity of NF-κB in skin tumor. Consistently, menthol-treated tumors also showed significantly suppressed the Ras-Raf-ERK signaling pathway. Thus, our results suggest that menthol inhibits DMBA/TPA-induced skin tumorigenesis by attenuating the Ras and inhibiting NF-κB activity via inhibition of inflammation responses and pro-inflammatory cytokine release.

Xanthatin, a sesquiterpene lactone purified from Xanthium strumarium L., possesses prominent anticancer activity. We found that disruption of GSK3β activity was essential for xanthatin to exert its anticancer properties in non-small cell lung cancer (NSCLC), concurrent with preferable suppression of constitutive activation of STAT3. Interestingly, inactivation of the two signals are two mutually exclusive events in xanthatin-induced cell death. Moreover, we surprisingly found that exposure of xanthatin failed to trigger the presumable side effect of canonical Wnt/β-Catenin followed by GSK3β inactivation. We further observed that the downregulation of STAT3 was required for xanthatin to fine-tune the risk. Thus, the discovery of xanthatin, which has ability to simultaneously orchestrate two independent signaling cascades, may have important implications for screening promising drugs in cancer therapies.

Our previous studies have shown that the best compatibility of components in Corni Fructus (PC) had a protective effect on vascular endothelial cells. In this study, the effect of PC on WT1 expression in glomerular podocytes and the mechanism of PC on early nephropathy in type 2 diabetic rats have been investigated. Type 2 diabetic rats were generated by high-fat diet combined with intraperitoneal injection of 30 mg/kg streptozotocin (STZ), then fed aminoguanidine (100 mg/kg), glimepiride (0.4 mg/kg), low-dose (60 mg/kg) or high-dose (120 mg/kg) of PC once a day for 12 weeks. Fasting blood glucose (FBG) was examined regularly. Insulin (INS) was measured by a radioimmunoassay. Microalbuminuria (mALB) was measured by an ELISA assay. Urinary creatinine (UCr), blood urea nitrogen (BUN) and N-acetyl-β-D-glucosaminidase (NAG) were measured by colorimetric assays. Renal morphological changes were observed by optical microscopy. The expression index of Wilms tumor 1 (WT1EI) in glomeruli was examined by immunohistochemistry. The results showed that PC led to a decrease in FBG (p < 0.01), NAG (p < 0.05) and mALB (p < 0.05) and an increase in INS (p < 0.01) and WT1EI (p < 0.05) compared to the diabetic group. PC could improve renal damage and greatly reduce the renal morphology score (p < 0.05). These results suggested that PC had the protective effect on early nephropathy in type 2 diabetic rats, which was closely related to the regulation of podocytes.