OBJECTIVE: This study aimed to determine the relationship between dietary intake (macronutrients, fruits, vegetables and lycopene), lifetime physical activity and oxidative DNA damage with prostate cancer.
DESIGN: A case control study was carried out among 105 subjects (case n=35, control n=70), matched for age and ethnicity. Data on sociodemographic, medical, dietary intake, consumption of lycopene rich food and lifetime physical activity were obtained through an interview based questionnaire. Anthropometric measurements including weight, height and waist hip circumferences were also carried out on subjects. A total of 3 mL fasting venous blood was drawn to assess lymphocyte oxidative DNA damage using the alkaline comet assay.
RESULTS: Cases had a significantly higher intake of fat (27.7 ± 5.5%) as compared to controls (25.1 ± 5.9%) (p < 0.05). Mean intakes of fruits and vegetables (3.11 ± 1.01 servings/d)(p < 0.05), fruits (1.23 ± 0.59 servings/d) (p<0.05) and vegetables (1.97 ± 0.94 servings/d) were higher in controls than cases (2.53 ± 1.01, 0.91 ∓ 0.69, 1.62 ± 0.82 servings/d). A total of 71% of cases did not met the recommendation of a minimum of three servings of fruits and vegetables daily, as compared to 34% of controls (p < 0.05) (adjusted OR 6.52 (95% CI 2.3-17.8)) (p < 0.05). Estimated lycopene intake among cases (2,339 ∓ 1,312 mcg/d) were lower than controls (3881 ∓ 3120 mcg/d) (p< 0.01). Estimated lycopene intake of less than 2,498 mcg/day (50th percentile) increased risk of prostate cancer by double [Adjusted OR 2.5 (95%CI 0.99-6.31)]. Intake of tomatoes, watermelon, guava, pomelo, papaya, mango, oranges, dragon fruit, carrot, tomato sauce and barbeque sauce were higher in controls compared to cases. Intake of tomato sauce of more than 2.24 g/d (25th percentile), papaya more than 22.7 g/d (50th percentile) and oranges more than 19.1g/h (50th percentile) reduced prostate cancer risk by 7.4 (Adjusted OR 7.4 (95% CI 1.17-46.8)), 2.7 (adjusted OR 2.75 (95% CI 1.03-7.39)) and 2.6 times (adjusted OR = 2.6 (95% CI=1.01-6.67)), respectively (p < 0.05 for all parameters). No oxidative damage was observed among subjects. Past history of not engaging with any physical activities at the age of 45 to 54 years old increased risk of prostate cancer by approximately three folds (Adjusted OR 2.9(95% CI = 0.8-10.8)) (p < 0.05). In conclusion, low fat diet, high intake of fruits, vegetables and lycopene rich foods and being physical active at middle age were found to be protective. Thus, it is essential for Malaysian men to consume adequate fruits and vegetables, reduce fat intake and engage in physical activity in order to reduce prostate cancer risk.
METHODS: MTT assay was performed to evaluate the cytotoxic effects of both compounds toward the cells after 24, 48 and 72 hours of exposure or treatment. The alkaline comet assay was conducted to determine the DNA damage on K562 cells after been exposed to both compounds for 30, 60 and 90 minutes.
RESULTS: The IC50 values obtained from K562 cells ranged from 0.01 to 0.30 μM, whereas for both Chang liver cell and lung fibroblast V79 cell, the values ranged from 0.10 to 0.40 μM. For genotoxicity evaluation, the percentage of damaged DNA is measured as an average of tail moment, and was found to be within 1.20 to 2.20 A.U while the percentage of DNA intensity ranging from 1.50 to 3.50% indicating no genotoxic effects.
CONCLUSION: Both compounds are cytotoxic toward leukemia cells and non-cancerous cells but do not exert their genotoxic effects towards leukemia cell.
RESULTS: The FLDP-5 and FLDP-8 curcuminoid analogues induced LN-18 cell death through apoptosis in a concentration-dependent manner following 24 h of treatment. These analogues induced apoptosis in LN-18 cells through significant loss of mitochondrial mass and mitochondrial membrane potential (MMP) as early as 1-hour of treatment. Interestingly, N-acetyl-l-cysteine (NAC) pretreatment did not abolish the apoptosis induced by these analogues, further confirming the cell death process is independent of ROS. However, the apoptosis induced by the analogues is caspases-dependent, whereby pan-caspase pretreatment inhibited the curcuminoid analogues-induced apoptosis. The apoptotic cell death progressed with the activation of both caspase-8 and caspase-9, which eventually led to the activation of caspase-3, as confirmed by immunoblotting. Moreover, the existing over-expression of miRNA-21 in LN-18 cells was suppressed following treatment with both analogues, which suggested the down-regulation of the miRNA-21 facilitates the cell death process.
CONCLUSION: The FLDP-5 and FLDP-8 curcuminoid analogues downregulate the miRNA-21 expression and induce extrinsic and intrinsic apoptotic pathways in LN-18 cells.