Investigation of the TLR4 and IRF3 signaling pathway-mediated effects of monensin in colorectal cancer cells.

Monensin is an ionophore antibiotic isolated from Streptomyces cinnamonensis with very strong antibacterial and antiparasitic effects. Although monensin is known to exhibit anticancer activity in different cancer types, there are a very limited number of studies on its anti-inflammatory effects in colorectal cancer (CRC) cells. The aim of this study was to investigate the TLR4/IRF3-mediated antiproliferative and anti-inflammatory effects of monensin in colorectal cancer cells. The dose- and time-dependent antiproliferative activity of monensin in colorectal cancer cells was determined by XTT method and its effects on mRNA expression changes of Toll-like receptors and IRF3 genes were determined by RT-PCR. TLR4 and Interferon Regulatory Factor 3 (IRF3) protein expression was evaluated by immunofluorescence method. TLR4 and type 1 interferon (IRF) levels were also evaluated by ELISA. IC50 value of monensin in HT29 cells was determined as 10.7082 µM at 48 h and 12.6288 µM at 48th for HCT116 cells. Monensin treatment decreased TLR4 and TLR7 and IRF3 mRNA expression in CRC cells. Monensin treatment decreased the expression level of IRF3 induced by LPS. Our study demonstrates for the first time the TLR4/IRF3-mediated anti-inflammatory effects of monensin in colorectal cancer cells. Further studies on the effects of monensin on TLR receptors in colorectal cancer cells are needed.

Erianin as a Promising Novel Agent in the Treatment of Neuroblastoma: The Anticancer Effects and Underlying Molecular Mechanisms.

BACKGROUND: Erianin is an active dibenzyl compound isolated from Dendrobium officinale and Dendrobium chrysotoxum and there are very few studies on molecular mechanisms and drug targets of erianin. In addition, there is no study investigating the anti-cancer effect of erianin on neuroblastoma cells. OBJECTIVE: The aim of the study is to investigate the anticancer effect of erianin and the underlying mechanism of this effect on SH-SY5Y cells. METHODS: The effects of erianin on cell viability, invasion and migration were determined by XTT, matrigel chamber and wound healing evaluation, respectively. Expression changes of miRNAs (microRNA) and apoptosis-related genes were evaluated by RT-PCR, and the apoptosis rate was supported by Annexin V evaluation. RESULTS: Erianin significantly decreased cell proliferation, invasion and migration. Erianin administration caused apoptosis by significantly increasing caspase-7, FADD (Fas-associated protein with death domain), BID (BH3 Interacting Domain Death Agonist) and DR5 (Death receptor 5) gene expressions. While the rate of total apoptotic cells was 45.35 ± 6.80% in SH-SY5Y cells treated with erianin, it was 0.133 ± 0.05% in the control group (p = 0.000). In addition, erianin administration significantly decreased the expressions of hsa-miR-155-5p (p = 0.014) and hsa-miR-223-3p (p = 0.004). Also, our study demonstrated for the first time the relationship between erianin and mi-RNAs in a cancer cell. CONCLUSION: Our study suggests that erianin may be a natural, safe and easily accessible drug candidate that can be used in the treatment of neuroblastoma.