Sulforaphane suppresses bladder cancer metastasis via blocking actin nucleation-mediated pseudopodia formation.

Metastasis is the primary stumbling block to the treatment of bladder cancer (BC). In order to spread, tumor cells must acquire increased migratory and invasive capacity, which is tightly linked with pseudopodia formation. Here, we unravel the effects of sulforaphane (SFN), an isothiocyanate in cruciferous vegetables, on the assembly of pseudopodia and BC metastasis, and its molecular mechanism in the process. Our database analysis revealed that in bladder tumor, the pseudopodia-associated genes CTTN, WASL and ACTR2/ARP2 are upregulated. SFN caused lamellipodia to collapse in BC cells by blocking the CTTN-ARP2 axis. SFN inhibited invadopodia formation and cell invasion by reducing WASL in different invasive BC cell lines. The production of ATP, essential for the assembly of pseudopodia, was significantly increased in bladder tumors and strongly inhibited by SFN. Overexpressing AKT1 reversed the downregulation of ATP in SFN-treated bladder cancer cells and restored filopodia and lamellipodia morphology and function. Bioluminescent imaging showed that SFN suppressed BC metastases to the lung of nude mice by downregulating Cttn and Arp2 expression. Our study reveals the mechanism of SFN action in inhibiting pseudopodia formation, and highlights potential targeting options for the therapy of metastatic bladder cancer.

Fatty foods and the risk of bladder cancer: A case-control study.

OBJECTIVE: The aim of this study was to explore the association between dietary fatty foods and the risk for bladder cancer. METHODS: Patients newly diagnosed with bladder cancer (n = 113) and 292 controls were recruited. A food frequency questionnaire (FFQ) was used to investigate the food intake within 1 y. Multivariate logistic regression model was used to estimated odds ratio (OR) between different types of fatty food consumption and bladder cancer. RESULTS: The consumption of soybean oil, the largest proportion of cooking oil, in both groups were much higher than the Chinese recommended dietary intake, especially in the control group. Higher intake of red meat was also observed in bladder cancer cases, although lower intakes of marine fish, egg, milk, and dairy products and nuts were observed in controls. After adjusting for potential confounders, the intakes of marine fish and milk and dairy products were negatively correlated with bladder cancer, with the adjusted OR of 0.28 (95% confidence interval [CI], 0.15-0.55) and 0.36 (95% CI, 0.19-0.69). Total nuts were related to a 76% reduction in bladder cancer risk (OR, 0.24; 95% CI, 0.12-0.48). There was clear and positive association between soybean oil and bladder cancer risk with OR of 3.47 (95 % CI, 1.69-7.14). In stratified analyses by sex and smoking status, the relationship was similar for most results, except for milk and dairy products. The negative correlation between milk and dairy products and bladder cancer risk was only found in men; and milk and dairy products and bladder cancer risk were irrelevant by smoking status. No significant association was found between the intakes of other foods and bladder cancer risk. CONCLUSIONS: Intake of nuts and marine fish may be beneficial for the prevention of bladder cancer. The protective effect of milk and dairy products was only found in men with bladder cancer. High soybean oil intake was a risk factor for bladder cancer.

Germinated Brown rice enhanced n-3 PUFA metabolism in type 2 diabetes patients: A randomized controlled trial.

BACKGROUND: Brown rice (BR) has been considered as a potential strategy in improving T2DM. However, there are a lack of population-based trials on the association of Germinated brown rice (GBR) and diabetes. AIMS: We aimed to explore the influence of GBR diet in T2DM patients for 3 months and whether this effect relates to serum fatty acids. METHODS: Two hundred and twenty T2DM patients have been enrolled and eligible subjects (n = 112, 61 female, 51 male) were randomly divided into GBR intervention group (n = 56) and control group (n = 56). Except those who lost follow-up and withdrew, final GBR group and control group consisted of 42 and 43 patients, respectively. Participants in GBR group were asked to consume 100 g/d GBR instead of equal refined grain (RG) for 3 months, while control group maintain their usual eating habits. A structured questionnaire was used for demographic information at baseline, and basic indicators were measured both at the beginning and end of the trail to evaluate plasma glucose and lipids levels. RESULTS: In GBR group, mean dietary inflammation index (DII) decreased, indicating GBR intervention retarded patient inflammation. Besides, glycolipid related parameters, including FBG, HbA1c, TC and HDL, were all significantly lower than those in control group. Excitingly, fatty acid composition was changed by intake of GBR, especially n-3 PUFA and n-3/n-6 PUFA rate were significantly increased. Moreover, subjects in GBR group had higher levels of n-3 metabolites, such as RVE, MaR1 and PD1, reducing inflammatory effect. In contrast, n-6 metabolites, like LTB4 and PGE2 which could promote inflammatory effect, were lower in GBR group. CONCLUSION: We confirmed that diet with 100 g/d GBR for 3 months could really improve T2DM to some extent. This beneficial effect may be related to n-3 metabolites, namely inflammation changes. TRIAL REGISTRATION: ChiCRT-IOR-17013999, www.chictr.org.cn.

AKT1/HK2 Axis-mediated Glucose Metabolism: A Novel Therapeutic Target of Sulforaphane in Bladder Cancer.

SCOPE: Metabolic disorder is a pivotal hallmark of cancer cells. Sulforaphane (SFN) is reported to improve lipid metabolism. However, the effect of SFN on glucose metabolism in bladder cancer remains unclear. Hence, the effect and underling mechanism is investigated. METHODS AND RESULTS: Biological samples from bladder cancer patients are collected, and also investigated using N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder cancer mice and bladder cancer cell lines. A novel glucose transport aberrant-independent aerobic glycolysis is found in bladder cancer patients, and the lower malignancy tissues have the more obvious abnormality. SFN strongly downregulates ATP production by inhibiting glycolysis and mitochondrial oxidative phosphorylation (OXPHOS). Both in vitro cell culture and in bladder tumor mice, SFN weaken the glycolytic flux by suppressing multiple metabolic enzymes, including hexokinase 2 (HK2) and pyruvate dehydrogenase (PDH). Moreover, SFN decreases the level of AKT1 and p-AKT ser473 , especially in low-invasive UMUC3 cells. The downregulation of ATP and HK2 by SFN is both reversed by AKT1 overexpression. CONCLUSIONS: SFN downregulates the unique glucose transport aberrant-independent aerobic glycolysis existed in bladder cancer via blocking the AKT1/HK2 axis and PDH expression.