Prostate cancer is the most commonly diagnosed malignancy in men and shows a predilection for metastasis to the bone. D-pinitol, a 3-methoxy analogue of d-chiro-inositol, was identified as an active principle in soy foods and legumes, and it has been proven to induce tumor apoptosis and metastasis of cancer cells. In this study, we investigated the anti-metastasis effects of D-pinitol in human prostate cancer cells. We found that D-pinitol reduced the migration and the invasion of prostate cancer cells (PC3 and DU145) at noncytotoxic concentrations. Integrins are the major adhesive molecules in mammalian cells and have been associated with the metastasis of cancer cells. Treatment of prostate cancer cells with D-pinitol reduced mRNA and cell surface expression of αvβ3 integrin. In addition, D-pinitol exerted its inhibitory effects by reducing focal adhesion kinase (FAK) phosphorylation, c-Src kinase activity and NF-κB activation. Thus, D-pinitol may be a novel anti-metastasis agent for the treatment of prostate cancer metastasis.

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BackgroundThe effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with diabetes mellitus (DM) remain unknown. We investigated the effects of oxybutynin, solifenacin and tolterodine on dementia risk in patients with DM.MethodsWe conducted a cohort study by using the diabetes dataset of the Taiwan National Health Insurance Research Database from 1 January, 2002 to 31 December, 2013. We included 10,938 patients received one type of oxybutynin, solifenacin, or tolterodine, while 564,733 had not. We included a comparable number of patients not receiving oxybutynin, solifenacin, or tolterodine as controls through systematic random sampling matching by age, gender, and the year of the index date with 1 to 1 ratio. The dementia risk was estimated through multivariate Cox proportional hazard regression after adjustment for several confounding factors.ResultsThe dementia event rates were 3.9% in the oxybutynin group, 4.3% in the solifenacin group, 2.2% in the tolterodine group and 1.2% in the control group (P<0.001). The adjusted HRs compared to nonusers of anticholinergic drugs were 2.35 (95% CI, 1.96 to 2.81), 2.16 (95% CI, 1.81 to 2.58), and 2.24 (95% CI, 1.85 to 2.73), respectively, for patients receiving oxybutynin, solifenacin, or tolterodine.ConclusionOur study indicates an association between taking oxybutynin, solifenacin and tolterodine and the subsequent diagnosis of dementia in DM patients. Moreover, the patients using oxybutynin had highest risk. The impact of these three drugs on risk of dementia in non-diabetic populations is warrant.

Tanshinone IIA (Tan-IIA), one of the major lipophilic components isolated from the root of Salviae Miltiorrhizae, has been found to exhibit anticancer activity in various cancer cells. We have demonstrated that Tan-IIA induces apoptosis in several human cancer cells through caspase- and mitochondria-dependent pathways. Here we explored the anticancer effect of Tan-IIA in human bladder cancer cell lines. Our results showed that Tan-IIA caused bladder cancer cell death in a time- and dose-dependent manner. Tan-IIA induced apoptosis through the mitochondria-dependent pathway in these bladder cancer cells. Tan-IIA also suppressed the migration of bladder cancer cells as revealed by the wound healing and transwell assays. Finally, combination therapy of Tan-IIA with a lower dose of cisplatin successfully killed bladder cancer cells, suggesting that Tan-IIA can serve as a potential anti-cancer agent in bladder cancer.

Cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR). In this study, we further demonstrated that CDT suppresses the IR-induced autophagy pathway in PCa cells by attenuating c-Myc expression and therefore sensitizes PCa cells to radiation. We further showed that CDT prevents the formation of autophagosomes via decreased high-mobility group box 1 (HMGB1) expression and the inhibition of acidic vesicular organelle (AVO) formation, which are associated with enhanced radiosensitivity in PCa cells. The results of this study reveal the detailed mechanism of CDT for the treatment of radioresistant PCa.

BackgroundThis nationwide population-based study investigated the risk of cardiovascular diseases after 5-alpha-reductase inhibitor therapy for benign prostate hyperplasia (BPH) using the National Health Insurance Research Database (NHIRD) in Taiwan.MethodsIn total, 1,486 adult patients newly diagnosed with BPH and who used 5-alpha-reductase inhibitors were recruited as the study cohort, along with 9,995 subjects who did not use 5-alpha-reductase inhibitors as a comparison cohort from 2003 to 2008. Each patient was monitored for 5 years, and those who subsequently had cardiovascular diseases were identified. A Cox proportional hazards model was used to compare the risk of cardiovascular diseases between the study and comparison cohorts after adjusting for possible confounding risk factors.ResultsThe patients who received 5-alpha-reductase inhibitor therapy had a lower cumulative rate of cardiovascular diseases than those who did not receive 5-alpha-reductase inhibitor therapy during the 5-year follow-up period (8.4% vs. 11.2%, P=0.003). In subgroup analysis, the 5-year cardiovascular event hazard ratio (HR) was lower among the patients older than 65 years with 91 to 365 cumulative defined daily dose (cDDD) 5-alpha-reductase inhibitor use (HR=0.63, 95% confidence interval (CI) 0.42 to 0.92; P=0.018), however there was no difference among the patients with 28 to 90 and more than 365 cDDD 5-alpha-reductase inhibitor use (HR=1.14, 95% CI 0.77 to 1.68; P=0.518 and HR=0.83, 95% CI 0.57 to 1.20; P=0.310, respectively).Conclusions5-alpha-reductase inhibitor therapy did not increase the risk of cardiovascular events in the BPH patients in 5 years of follow-up. Further mechanistic research is needed.

Klebsiella pneumoniae is the predominant pathogen isolated from liver abscess of diabetic patients in Asian countries. With the spread of multiple-drug-resistant K. pneumoniae, there is an increasing need for the development of alternative bactericides and approaches to block the production of bacterial virulence factors. Capsular polysaccharide (CPS), especially from the K1 and K2 serotypes, is considered the major determinant for K. pneumoniae virulence. We found that extracts of the traditional Chinese medicine Fructus mume inhibited the growth of K. pneumoniae strains of both serotypes. Furthermore, Fructus mume decreased the mucoviscosity, and the CPS produced in a dose-dependent manner, thus reducing bacterial resistance to serum killing. Quantitative reverse transcription polymerase chain reaction analyses showed that Fructus mume downregulated the mRNA levels of cps biosynthesis genes in both serotypes, possibly by increasing the intracellular iron concentration in K. pneumoniae. Moreover, citric acid, a major organic acid in Fructus mume extracts, was found to have an inhibitory effect on growth and CPS biosynthesis in K. pneumoniae. Taken together, our results indicate that Fructus mume not only possesses antibacterial activity against highly virulent K. pneumoniae strains but also inhibits bacterial CPS biosynthesis, thereby facilitating pathogen clearance by the host immune system.

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