Currently available studies have suggested that a number of exosome-encapsulated microRNAs (miRNAs) are recognized as stable biomarkers for cancers. However, little is known about the effect of exosomal miRNAs on colorectal cancer (CRC). The aim of study is to identify specific miRNAs in serum exosomes, which may serve as potential diagnostic and prognostic biomarkers and therapeutic targets for CRC. Microarray analyses of miRNAs in serum exosomes from 3 primary CRC patients and 3 healthy controls were performed. Those differentially expressed exosome-encapsulated miRNAs were verified in exosome-enriched serum samples from 77 CRC patients and 20 healthy controls by quantitative real-time PCR (qRT-PCR). A total of 39 aberrantly expressed miRNAs in serum exosomes were identified by microarray analysis. After confirmation by qRT-PCR, we found that 5 exosome-encapsulated miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p and miR-548c-5p) were significantly down-regulated, while 2 exosome-encapsulated miRNAs (miR-486-5p and miR-3180-5p) were significantly up-regulated in serum. Decreased levels of miR-638 in serum exosomes were associated with increased risk of liver metastasis and later TNM stage of CRC. Networks analyses revealed that 5 aberrantly expressed miRNAs (miR-638, miR-5787, miR-8075, miR-6869-5p, and miR-548c-5p) might be involved in the process of glucose metabolism in CRC. The present study shows the specific serum profile of exosome-encapsulated miRNAs in CRC. Those specific miRNAs in serum exosomes may serve as disease biomarkers and novel therapeutic targets for CRC.

Cancer is a common malignant disease worldwide with an increasing mortality in recent years. Salvia miltiorrhiza, a well-known traditional Chinese medicine, has been used for the treatment of cardiovascular and cerebrovascular diseases for thousands of years. The liposoluble tanshinones in S. miltiorrhiza are important bioactive components and mainly include tanshinone IIA, dihydrodanshinone, tanshinone I, and cryptotanshinone. Previous studies showed that these four tanshinones exhibited distinct inhibitory effects on tumor cells through different molecular mechanisms in vitro and in vivo. The mechanisms mainly include the inhibition of tumor cell growth, metastasis, invasion, and angiogenesis, apoptosis induction, cell autophagy, and antitumor immunity, and so on. In this review, we describe the latest progress on the antitumor functions and mechanisms of these four tanshinones to provide a deeper understanding of the efficacy. In addition, the important role of tumor immunology is also reviewed.

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The limited bioavailability of plant-derived natural products with anticancer activity poses major challenges to the pharmaceutical industry. An example of this is camptothecin, a monoterpene indole alkaloid with potent anticancer activity that is extracted at very low concentrations from woody plants. Recently, camptothecin biosynthesis has been shown to become biotechnologically amenable in hairy-root systems of the natural producer Ophiorrhiza pumila. Here, time-course expression and metabolite analyses were performed to identify novel transcriptional regulators of camptothecin biosynthesis in O. pumila. It is shown here that camptothecin production increased over cultivation time and that the expression pattern of the WRKY transcription factor encoding gene OpWRKY2 is closely correlated with camptothecin accumulation. Overexpression of OpWRKY2 led to a more than three-fold increase in camptothecin levels. Accordingly, silencing of OpWRKY2 correlated with decreased camptothecin levels in the plant. Further detailed molecular characterization by electrophoretic mobility shift, yeast one-hybrid and dual-luciferase assays showed that OpWRKY2 directly binds and activates the central camptothecin pathway gene OpTDC. Taken together, the results of this study demonstrate that OpWRKY2 acts as a direct positive regulator of camptothecin biosynthesis. As such, a feasible strategy for the over-accumulation of camptothecin in a biotechnologically amenable system is presented.

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Breast cancer (BC) is a prominent source of cancer mortality in women throughout the world. β-Sitosterol-d-glucoside (β-SDG), a newly isolated phytosterol from sweet potato, possibly displays potent anticancer activity. However, the probable anticancer mechanisms involved are still unclear. This study sought to study how β-SDG from sweet potato affects two BC cell lines (MCF7 and MDA-MB-231) and nude mice bearing MCF7-induced tumors. In addition, we assessed how β-SDG affects tumor suppressor miR-10a and PI3K-Akt signaling in BC cells. Cell viability and proliferation were determined via MTT and colony-formation assays, and apoptosis was quantified by Hoechst staining and flow cytometry. In addition, miR-10a expression and apoptosis-related protein levels were measured. Our study indicated that β-SDG exhibited cytotoxic activities on MCF7 and MDA-MB-231 cells via inducing apoptosis and activating caspase proteases in these cells. Furthermore, the experimental results in nude mice bearing MCF7-induced tumors demonstrated that oral β-SDG administration at medium (60 mg/kg) or high (120 mg/kg) doses was sufficient to substantially impair the growth of tumors and to decrease the levels of CEA, CA125, and CA153 by 64.71, 74.64, and 85.32%, respectively, relative to those of the controls ( P < 0.01). β-SDG was further found to regulate the expression of PI3K, p-Akt, Bcl-2-family members, and other factors involved in the PI3K-Akt-mediated mitochondrial signaling pathway via the tumor suppressor miR-10a. These findings indicated that β-SDG suppresses tumor growth by upregulating miR-10a expression and inactivating the PI3K-Akt signaling pathway. Furthermore, β-SDG could be developed as a potential therapeutic agent against MCF7-cell-related BC.

Cancer stem-like cells are closely related with the development and metastasis of tumors. Herein, an electrochemical method is proposed to identify stem-like cells in breast tumor. The core concept of the method is the use of multifunctional nanofibers (MNFs), which are synthesized through facile self-assembly of peptide probes. MNFs can perform three functions, specifically targeting surface biomarker to identify stem-like cells, recruiting silver nanoparticles (AgNPs) to generate electrochemical signals, and providing large amounts of reaction sites to amplify signals. Specially, breast cancer stem cells (BCSCs) are first captured by nucleolin aptamer immobilized on the electrode surface and then selectively recognized by MNFs through the binding with CD44, thereby offering a large number of azide groups for signal labeling. By tracing electrochemical signals from MNF-recruited AgNPs, the method demonstrates to detect target cells as low as 6 cells/mL within a wide linear range from 10 to 5 × 105 cells/mL. Moreover, the method can not only recognize BCSCs with high selectivity in complex environment but also monitor drug-induced stemness changes with high sensitivity, providing promising prospective clinic applications in the future.

This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7?mg/kg???day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7?-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches.