Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly discovered long-chain fatty acids. However, the major endogenous FAHFAs in healthy human circulation, their correlation with cardiovascular (CV) biomarkers, and their anti-inflammatory effects have not been investigated and remain unclear. In the present study, a total of 57 healthy subjects were recruited. Liquid chromatography–mass spectrometry (LC-MS) was developed for the simultaneous determination of seven FAHFAs, four long-chain fatty acids, and four non-traditional circulating CV-related biomarkers. We found two major types of FAHFAs in healthy human circulation, palmitoleic acid ester of 9-hydroxystearic acid (9-POHSA), and oleic acid ester of 9-hydroxystearic acid (9-OAHSA). Both 9-POHSA and 9-OAHSA had a strong positive correlation with each other and were negatively correlated with fasting blood glucose, S-adenosyl-l-homocysteine (SAH), and trimethylamine N-oxide (TMAO), but not with l-homocysteine. 9-POHSA was also positively correlated with l-carnitine. Moreover, we confirmed that both 9-POHSA and 9-OAHSA exhibited an anti-inflammatory effect by suppressing LPS stimulated cytokines, including IL-1β and IL-6 in RAW 264.7 cells. In addition, palmitoleic acid also had a positive correlation with 9-POHSA and 9-OAHSA. As far as we know, this is the first report showing the major endogenous FAHFAs in healthy subjects and their CV protection potential which might be correlated with SAH and TMAO reduction, l-Carnitine elevation, and their anti-inflammatory effects.

No abstract

Statins, also known as HMG-CoA reductase inhibitors, are a class of cholesterol-lowering drugs and their anti-cancer effects have been studied in different types of malignant diseases. In the present study, we investigated the anti-proliferative effects of statins, including cerivastatin and simvastatin, on oral squamous cell carcinoma (OSCC) cells. Our data showed that statins inhibited the proliferation of three OSCC cell lines in a dose-dependent manner and this growth inhibition was confirmed through G0/G1 cell cycle arrest. Accordingly, we found the upregulation of p21 and downregulation of cyclin-dependent kinases, including CDK2, CDK4, and CDK6, in the statin-treated cells. Importantly, we clearly showed that statins were able to inhibit the expression of DNA methyltransferase 1 (DNMT1) and further promote the expression of p21. Taken together, our data demonstrated that the anti-proliferative effect of statins is mediated by suppressing DNMT1 expression, thus promoting p21 expression and leading to G0/G1 cell cycle arrest in OSCC cells.

No abstract

Cryptotanshinone is a diterpene quinone derived from the roots of Salvia miltiorrhiza Bunge. An increasing number of studies have demonstrated that cryptotanshinone has the pharmacological activities such as anti-oxidative stress, anti-bacteria, anti-inflammation, and anti-cancer. Cryptotanshinone has been found to increase the ARE expression level induced by the Nrf2 and decrease Keap1 expression. This study investigated Nrf2 and Keap1-related microRNA to understand the mechanisms of cryptotanshinone in antioxidant activities. HepG2 cells were treated with cryptotanshinone 2.5 μM in DMEM medium with 1% FBS for 5 days. Total RNA was obtained for small RNA sequencing and real-time PCR analyses. The analyses revealed that Cryptotanshinone had the potential to inhibit miR-27a-5p, miR-142-5p, miR-28 and miR-93-5p levels, which subsequently increased the Nrf2 mRNA level. On the other hand, the Keap1 mRNA level was suppressed through up-regulation of miR-23a and down-regulation of miR-7-5p. Moreover, Nrf2 and its related downstream anti-oxidant enzymes such as NQO1 and UGT were increased and the Keap1 protein level was decreased. These findings suggest that cryptotanshinone possesses the cancer chemoprevention activity in up-regulation of Nrf2 mRNA and protein levels through the suppression of inhibitory microRNA. Future investigations that extend the current study can focus on pharmacological mechanism of cryptotanshinone as a cancer chemoprevention agent, and the safety of long-term uptake of cryptotanshinone for cancer prevention. Citation Format: Rachmad A. Dongoran, Tien-Yuan Wu. Cryptotanshinone activate Nrf2 expression through microRNA regulations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5269. doi:10.1158/1538-7445.AM2017-5269