8-Geranyloxycarbostyril as a potent 15-LOX-1 inhibitor showed great anti-tumor effects against prostate cancer.

Carbostyrils are quinolone derivatives, with possible growth inhibition properties on cancer cells. Unlike many tumors, 15-Lipoxygenase-1 (15-LOX-1) is highly expressed in prostate cancer (PCa) cells and has oncogenic properties. Here, with the hypothesis that 6-, 7- and 8-geranyloxycarbostyril (GQ) have inhibitory properties on 15-LOX-1, their effects were assessed on PCa cells. Their cytotoxic effects were evaluated by MTT assay and mechanism of cell death was investigated using annexin V/PI staining. Finally, the anti-tumor properties of 8-GQ were assessed in immunocompromised C57BL/6 mice bearing human PCa cells. Accordingly, these compounds could effectively inhibit 15-LOX activity in PCa cells. MTT and flow cytometry tests confirmed their toxic effects on PCa cells, with no significant toxicity on normal cells, and apoptosis was the main mechanism of cell death. In vivo results indicated that use of 8-GQ at 50 mg/kg had stronger anti-tumor effects than 5 mg/kg cisplatin, with fewer side effects on normal tissues. Therefore, 8-GQ can be introduced as a potential drug candidate with 15-LOX-1 inhibitory potency, which can be effective in treatment of prostate cancer, and should be considered for further drug screening investigations.

Role of microRNAs in osteogenesis of stem cells.

Osteogenic differentiation is a controlled developmental process in which external and internal factors including cytokines, growth factors, transcription factors (TFs), signaling pathways and microRNAs (miRNAs) play important roles. Various stimulatory and inhibitory TFs contribute to osteogenic differentiation and are responsible for bone development. In addition, cross-talk between several complex signaling pathways regulates the osteogenic differentiation of some stem cells. Although much is known about regulatory genes and signaling pathways in osteogenesis, the role of miRNAs in osteogenic differentiation still needs to be explored. miRNAs are small, approximately 22 nucleotides, single-stranded nonprotein coding RNAs which are abundant in many mammalian cell types. They paly significant regulated roles in various biological processes and serve as promising biomarkers for disease states. Recently, emerging evidence have shown that miRNAs are the key regulators of osteogenesis of stem cells. They may endogenously regulate osteogenic differentiation of stem cells through direct targeting of positive or negative directors of osteogenesis and depending on the target result in the promotion or inhibition of osteogenic differentiation. This review aims to provide a general overview of miRNAs participating in osteogenic differentiation of stem cells and explain their regulatory effect based on the genes targeted with these miRNAs.