RXRα-enriched cancer stem cell-like properties triggered by CDDP in head and neck squamous cell carcinoma (HNSCC).

Retinoid X receptor-α (RXRα) is a kind of nuclear receptor and is a target of cancer prevention and treatment in various types of cancers. Cancer stem cells (CSCs) are regarded as the main cause of carcinoma metastasis, tumor recurrence and chemotherapy resistance. So far, the mechanism how RXRα regulates CSCs remains unknown. In the present study, we found that RXRα was upregulated in head and neck squamous cell carcinoma (HNSCC) tissues and the enriched HNSCC CSCs. Overexpression of RXRα was able to expand the CSC-like properties in HNSCC cells, whereas knockdown of RXRα could repress the stemness respectively. Meanwhile, low doses of cisplatin (CDDP) increased the CSC-like properties and RXRα expression in HNSCC cells. Also, Wnt signaling pathway played a significant role in CDDP-induced CSCs. Simultaneously, curcumin, a plant polyphenol, which is an effective anticancer compound, exhibited an inhibitory effect in the HNSCC CSCs induced by CDDP in vitro and in vivo. Via inhibition of RXRα, curcumin suppressed CSC-like phenotypes induced by CDDP. These findings may suggest a novel mechanism for HNSCC treatment.

Protective Effects of Olive Leaf Extract on Acrolein-Exacerbated Myocardial Infarction via an Endoplasmic Reticulum Stress Pathway.

Many studies reported that air pollution particulate matter (PM) exposure was associated with myocardial infarction (MI). Acrolein representing the unsaturated aldehydes, the main component of PM, derives from the incomplete combustion of wood, plastic, fossil fuels and the main constitute of cigarette smoking. However, the effect of acrolein on MI remains not that clear. In the current study, the effect of acrolein-exacerbated MI was investigated. In vivo, male Sprague-Dawley rats received olive leaf extract (OLE) followed by acrolein, then isoprenaline (ISO) was received by subcutaneous injection to induce MI. Results showed that the expression levels of GRP78 and CHOP, two major components of endoplasmic reticulum (ER) stress were higher in the combination of acrolein and ISO than those in ISO treatment. The apoptosis marker, Bax, was also higher while the anti-apoptosis indicator, Bcl2 expression was lower both at protein and mRNA levels in the combination group. Also, the acrolein-protein adducts and myocardial pathological damage increased in the combination of acrolein and ISO relative to the ISO treatment. Besides, cardiac parameters, ejection fraction (EF) and fractional shortening (FS) were reduced more significantly when acrolein was added than in ISO treatment. Interestingly, all the changes were able to be ameliorated by OLE. Since hydroxytyrosol (HT) and oleuropein (OP) were the main components in OLE, we next investigated the effect of HT and OP on cardiomyocyte H9c2 cell apoptosis induced by acrolein through ER stress and Bax pathway. Results showed that GRP78, CHOP and Bax expression were upregulated, while Bcl2 expression was downregulated both at the protein and mRNA levels, when the H9c2 cells were treated with acrolein. In addition, pretreatment with HT can reverse the expression of GRP78, CHOP, Bax and Bcl2 on the protein and mRNA levels, while there was no effect of OP on the expression of GRP78 and CHOP on the mRNA levels. Overall, all these results demonstrated that OLE and the main components (HT and OP) could prevent the negative effects of acrolein on myocardium and cardiomyocytes.

Acrylamide induces HepG2 cell proliferation through upregulation of miR-21 expression.

Acrylamide, a potential carcinogen, exists in carbohydrate-rich foods cooked at a high temperature. It has been reported that acrylamide can cause DNA damage and cytotoxicity. The present study aimed to investigate the potential mechanism of human hepatocarcinoma HepG2 cell proliferation induced by acrylamide and to explore the antagonistic effects of a natural polyphenol curcumin against acrylamide via miR-21. The results indicated that acrylamide (≤100 µmol/L) significantly increased HepG2 cell proliferation and miR-21 expression. In addition, acrylamide reduced the PTEN expression in protein level, while induced the expressions of p-AKT, EGFR and cyclin D1. The PI3K/AKT inhibitor decreased p-AKT protein expression and inhibited the proliferation of HepG2 cells. In addition, curcumin effectively reduced acrylamide-induced HepG2 cell proliferation and induced apoptosis through the expression of miR-21. In conclusion, the results showed that acrylamide increased HepG2 cell proliferation via upregulating miR-21 expression, which may be a new target for the treatment and prevention of cancer.