Purpose: The existence of cancer stem cells (CSCs) in breast cancer has profound implications for cancer prevention. In this study, we evaluated sulforaphane, a natural compound derived from broccoli/broccoli sprouts, for its efficacy to inhibit breast CSCs and its potential mechanism. Experimental Design: Aldefluor assay and mammosphere formation assay were used to evaluate the effect of sulforaphane on breast CSCs in vitro. A nonobese diabetic/severe combined immunodeficient xenograft model was used to determine whether sulforaphane could target breast CSCs in vivo, as assessed by Aldefluor assay, and tumor growth upon cell reimplantation in secondary mice. The potential mechanism was investigated using Western blotting analysis and β-catenin reporter assay. Results: Sulforaphane (1-5 μmol/L) decreased aldehyde dehydrogenase–positive cell population by 65% to 80% in human breast cancer cells (P < 0.01) and reduced the size and number of primary mammospheres by 8- to 125-fold and 45% to 75% (P < 0.01), respectively. Daily injection with 50 mg/kg sulforaphane for 2 weeks reduced aldehyde dehydrogenase–positive cells by >50% in nonobese diabetic/severe combined immunodeficient xenograft tumors (P = 0.003). Sulforaphane eliminated breast CSCs in vivo, thereby abrogating tumor growth after the reimplantation of primary tumor cells into the secondary mice (P < 0.01). Western blotting analysis and β-catenin reporter assay showed that sulforaphane downregulated the Wnt/β-catenin self-renewal pathway. Conclusions: Sulforaphane inhibits breast CSCs and downregulates the Wnt/β-catenin self-renewal pathway. These findings support the use of sulforaphane for the chemoprevention of breast cancer stem cells and warrant further clinical evaluation. Clin Cancer Res; 16(9); 2580–90. ©2010 AACR.

Lycopene is a non-provitamin A carotenoid that is responsible for the red to pink colors seen in tomatoes, pink grapefruit, and other foods. Processed tomato products are the primary dietary lycopene source in the United States. Unlike many other natural compounds, lycopene is generally stable to processing when present in the plant tissue matrix. Recently, lycopene has also been studied in relation to its potential health effects. Although promising data from epidemiological, as well as cell culture and animal, studies suggest that lycopene and the consumption of lycopene containing foods may affect cancer or cardiovascular disease risk, more clinical trial data is needed to support this hypothesis. In addition, future studies are required to understand the mechanism(s) whereby lycopene or its metabolites are proven to possess biological activity in humans.

Background: The amount of dietary fat required for optimal bioavailability of carotenoids in plant matrices is not clearly defined. Objective: The objective was to quantify the appearance of carotenoids in plasma chylomicrons after subjects ingested fresh vegetable salads with fat-free, reduced-fat, or full-fat salad dressings. Design: The subjects (n = 7) each consumed 3 salads consisting of equivalent amounts of spinach, romaine lettuce, cherry tomatoes, and carrots with salad dressings containing 0, 6, or 28 g canola oil. The salads were consumed in random order separated by washout periods of ≥2 wk. Blood samples were collected hourly from 0 to 12 h. Chylomicrons were isolated by ultracentrifugation, and carotenoid absorption was analyzed by HPLC with coulometric array detection. Results: After ingestion of the salads with fat-free salad dressing, the appearance of α-carotene, β-carotene, and lycopene in chylomicrons was negligible. After ingestion of the salads with reduced-fat salad dressing, the appearance of the carotenoids in plasma chylomicrons increased relative to that after ingestion of the salads with fat-free salad dressing (P < 0.04). Similarly, the appearance of the carotenoids in plasma chylomicrons was higher after the ingestion of salads with full-fat than with reduced-fat salad dressing (P < 0.02). Conclusions: High-sensitivity HPLC with coulometric array detection enabled us to quantify the intestinal absorption of carotenoids ingested from a single vegetable salad. Essentially no absorption of carotenoids was observed when salads with fat-free salad dressing were consumed. A substantially greater absorption of carotenoids was observed when salads were consumed with full-fat than with reduced-fat salad dressing.

Dietary lipids are hypothesized to be an important factor for carotenoid bioavailability. However, most carotenoid-rich fruits and vegetables are low in lipids. The objective of this study was to assess whether the addition of avocado fruit as a lipid source enhances carotenoid absorption in humans. Healthy subjects (n = 11/study) were recruited for 2 crossover, postprandial studies. The effect of avocado addition (150 g) to salsa on lycopene and β-carotene absorption was examined in Study 1, and the absorption of lutein, α-carotene, and β-carotene from salad in Study 2. Furthermore, the effects of avocado dose (75 vs. 150 g containing 12 vs. 24 g lipid, respectively) and of lipid source (avocado fruit vs. avocado oil) on carotenoid absorption were examined in Study 2. Intact carotenoids were quantified in the plasma triacylglycerol-rich lipoprotein (TRL) fraction during the 9.5 h after consumption of the test meal and expressed as baseline-corrected area under the concentration-vs.-time curve (AUC). The addition of avocado to salsa enhanced lycopene and β-carotene absorption (P < 0.003), resulting in 4.4 and 2.6 times the mean AUC after intake of avocado-free salsa, respectively. In Study 2, supplementing 150 g avocado or 24 g avocado oil to salad similarly enhanced α-carotene, β-carotene, and lutein absorption (P < 0.01), resulting in 7.2, 15.3, and 5.1 times the mean AUC after intake of avocado-free salad, respectively (150 g avocado). Neither the avocado dose nor the lipid source affected carotenoid absorption. In conclusion, adding avocado fruit can significantly enhance carotenoid absorption from salad and salsa, which is attributed primarily to the lipids present in avocado.