Abstract
Traditional herb medicine, golden thread (Anoectochilus formosanus Hayata) has been used to treat various diseases. Hyperglycemia induces generation of reactive oxygen species (ROS) and enhancement of oxidative stress which are risk factors for cancer progression and metastasis. In this study, we evaluated hypoglycemic effect of A. formosanus extracts (AFEs) in an inducible hyperglycemia animal model and its capacity of free-radical scavenging to establish hyperglycemia-related carcinogenesis. AFE reduced blood glucose in hyperglycemic mice while there was no change in control group. The incremental area under blood glucose response curve was decreased significantly in hyperglycemic mice treated with AFE in a dose-dependent manner. AFE and metformin at the same administrated dose of 50 mg/kg showed similar effect on intraperitoneal glucose tolerance test in hyperglycemic mice. Free-radical scavenger capacity of AFE was concentration dependent and 200 μg/ml of AFE was able to reduce more than 41% of the free radical. Treatment of cancer cells with AFE inhibited constitutive PD-L1 expression and its protein accumulation. It also induced expression of pro-apoptotic genes but inhibited proliferative and metastatic genes. In addition, it induced anti-proliferation in cancer cells. The results suggested that AFE not only reduced blood glucose concentration as metformin but also showed its potential use in cancer immune chemoprevention/therapy via hypoglycemic effect, ROS scavenging and PD-L1 suppression.
Highlights
Hyperglycemia is the most prominent sign that characterizes diabetes (Kitabchi et al, 2009)
Recent evidence indicates that both hyperglycemia and hyperinsulinemia in diabetes may provoke cell damage responses, such as oxidative stress, glucotoxicity, and lipotoxicity involved in the cell transformation process to raise the risk of cancer development (Cignarelli et al, 2018)
Evidence has indicated that hyperglycemia promotes the acquirement of mesenchymal and cancer stem cells (CSC) properties in malignant pancreatic ductal epithelial cells by activating TGF-β signaling (Rahn et al, 2018)
Summary
Hyperglycemia is the most prominent sign that characterizes diabetes (Kitabchi et al, 2009). The most commonly prescribed drug for type II diabetes, is constantly associated with decreased risk of the occurrence of various types of cancers, especially of pancreas (Rahn et al, 2018), colon (Anisimov, 2016), and hepatocellular carcinoma (Donadon et al, 2010) This observation is confirmed by the results of numerous metaanalyses. Hyperglycemia has been shown to induce changes in neutrophil mobilization, primary tumor growth, and metastatic progression (Fainsod-Levi et al, 2017) It is associated with significantly higher rates of cancer-related deaths, in gastrointestinal cancer and leukemia, but not with non-cancerrelated deaths (Simon et al, 2018). The hypothesis is that A. formosanus extract (AFE) may be able to inhibit hyperglycemia-induced production of ROS, to reduce blood glucose and to suppress the expression of PD-L1 in fructoseinduced hyperglycemic mice model for the cancer prevention. These results suggest that AFE can be used in cancer immune chemoprevention or chemotherapy in the future
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
