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Silencing Y-box binding protein 1 (YB-1) can be an excellent target for cancer therapy and many lung cancer cells express the polysaccharide-recognition receptor Dectin-1. We designed a Dectin-1 targeting vehicle delivering YB-1-antisense DNA. First, we selected five optimal antisense DNA sequences to silence YB-1 from among 153 candidates. We chose the sequence closest to the start codon (AS014), and attached dA40 to the 3' end; dA40 promotes complex formation with a β-(1➝3)-d-glucan called schizophyllan (SPG). The resultant complexes were applied to 12 human-oriented lung cancer cell lines, and cell viability was examined. The cell lines exhibited decreased viability and showed strong affinity to bind SPG, suggesting the AS014/SPG complex entered the cells via the Dectin-1 mediated pathway.

Circadian rhythms regulate a variety of physiological functions. Epidemiological evidence indicates that disruption of these circadian rhythms might be linked to cancer. In general, imbalances in homeostasis, such as immune and hormonal dysfunctions, are thought to be involved in cancer development. The results of a recent study suggested that circadian disruption may induce stromal changes associated with cancer risk, highlighting the importance of the cancer stem cell niche for protecting cancer cells. Current research provides new concepts and clarification regarding the function of the tumor niche, and the new concept of a stromal niche may help us to understand the additional functions of both cancer-associated fibroblasts and the extracellular matrix. In this review, we summarize our current knowledge regarding the role of circadian rhythms in cancer risk and the relevance of the stromal niche in cancer cell survival and progression.

Telomeres of human chromosomes consist of a repeated TTAGGG sequence, and at the terminal of this repeat sequence, the 3' strand is longer than the 5' strand. In this study, we characterized single and double stranded telomere binding proteins (ssTBPs and dsTBPs) by gel mobility shift assay and South-Western blotting assay. At least two protein components with molecular weights of 29 and 33 kDa were bound to a single stranded telomeric sequence, and also two proteins with molecular weights of about 44 kDa and 70 kDa were bound to a double stranded telomeric sequence. A competition assay demonstrated that the binding properties of ssTBPs and dsTBPs were specific to the telomeric sequence. We further cloned a ssTBP cDNA (ssTBP-1) by screening a lambda-gt11 expression library and identified ssTBP-1 as a human heterogeneous nuclear ribonucleoprotein (hnRNP) Al on the basis of cDNA sequence. We also found that the expression of the hnRNP Al gene significantly decreased during in vitro passage of human microvascular endothelial cells.

Flavin adenine dinucleotide (FAD) is an essential coenzyme for glutathione reductase (GR) which catalyzes the reduction of oxidized glutathione to regenerate the reduced form involved in protection against oxidative stress. Riboflavin kinase (RFK) also known as flavokinase is involved in the first step of bioactivation of riboflavin (RF) to form flavin mononucleotide (FMN) which can be subsequently converted to FAD in an ATP-dependent reaction catalyzed by FAD synthetase (FADS). We investigated the involvement of RFK in cisplatin resistance using human prostate cancer PC3 cells. RFK overexpression renders cells resistant not only to cisplatin but also to hydrogen peroxide (H2O2) and diamide. Furthermore, knockdown of RFK expression induced apoptosis. We demonstrated that overexpression of RFK increased the levels of FAD, FMN and total glutathione and the expression of GR and glutathione S-transferase-π (GSTπ). RFK expression is up-regulated in cisplatin-resistant P/CDP6 cells in addition to FAD, total glutathione level, GR and GSTπ. Knockdown of RFK expression also sensitized both PC3 and P/CDP6 cells to cisplatin. Moreover, cellular levels of RFK expression correlate well with Gleason score, known as a good indicator of patient prognosis. The present study suggests that RFK expression is involved not only in cellular protection from oxidative stress but also in malignant progression of prostate cancer.

Mitochondrial transcription factor A (mtTFA) is a member of the HMG (high mobility group)-box protein family. We previously showed that mtTFA preferentially binds to both cisplatin-damaged and oxidatively damaged DNA. In this study, we found that expression levels of both mtTFA and the mitochondrial antioxidant protein thioredoxin2 (TRX2) are upregulated in cisplatin-resistant cell lines. In addition, TRX2 directly interacts with mtTFA and enhances its damaged DNA binding activity. The interaction between mtTFA and TRX2 requires the HMG box 1 motif of mtTFA. Furthermore, when amino acid substitutions were introduced at either C49G or C246stop, TRX2 interacted with mtTFA. However, the interaction of TRX2 with mtTFA was enhanced when both mutations (C49G and C246stop) were introduced. Binding to cisplatin-damaged DNA was similar among mutant mtTFA proteins. By contrast, binding to oxidized DNA was significantly enhanced when double mutations were introduced. These results suggest that TRX2 not only functions as an antioxidant, but also supports mtTFA functions.