Lycopene: Multitargeted Applications in Cancer Therapy

Cancer is an uncontrolled growth and division of cells, leading to significant morbidity and mortality and economic burden to the society. Natural products as anticancer molecules have drawn the attention of researchers and have resulted in the development of many successful anticancer drugs, which include camptothecins, epipodophyllotoxins, vinca alkaloids, and taxanes. Another group of compounds with anti-cancer effects include botanicals (phytochemicals) found in the diet. In recent years, a tomato carotenoid lycopene (LYC) has gained attention for its potential health benefits, especially in prevention and treatment of cancer. The studies suggest that the consumption LYC in food or by itself may reduce cancer risk. However, there are insufficient clinical trial data to support the hypothesis. LYC may play a preventive role in a variety of cancers, especially in prostate cancer. It acts by multiple mechanisms including the regulation of growth factor signalling, cell cycle arrest and/or apoptosis induction, metastasis and angiogenesis, as well as by modulating the anti-inflammatory and phase II detoxification enzymes activities. The effects can be attributed to the unique chemical structure of the carotenoid which confers it a strong antioxidant property. In this chapter, we discuss the chemopreventive and anti-cancer properties of LYC, a dietary carotenoid.

Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats

We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR-α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations. Cinnamon polyphenol decreased body weight, visceral fat, liver weight and serum glucose and insulin concentrations, liver antioxidant enzymes, and lipid profile (P<0.05) and reduced serum and liver MDA concentration compared to HFD rats (P<0.05). Cinnamon polyphenol also suppressed the hepatic SREBP-1c, LXR-α, ACLY, FAS, and NF-κB p65 expressions and enhanced the PPAR-α, IRS-1, Nrf2, and HO-1 expressions in the HFD rat livers (P<0.05). In conclusion, cinnamon polyphenol reduces the hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathway in HFD rat liver

Lycopene Prevents Development of Steatohepatitis in Experimental Nonalcoholic Steatohepatitis Model Induced by High-Fat Diet

We investigated the preventive effect of lycopene on nonalcoholic steatohepatitis-induced by high-fat diet in rats. Forty male Sprague-Dawley rats were divided into 4 groups. They were fed standard diet, high-fat diet (HFD), high-fat diet plus lycopene at a dose of 2 mg/kg body weight and the high-fat diet lycopene at a dose of 4 mg/kg BW for a period of 6 weeks. Inflammation, steatosis, α-smooth muscle actin (α-SMA), and cytochrome P450 2E1 (CYP 2E1) expression increased significantly in the rats fed HFD and decreased in the rats administered by lycopene. Significantly elevated levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor (TNF α), and serum and liver malondialdehyde (MDA) were observed in rats fed the high-fat diet as compared to the control rats (P < .01). Supplementation with lycopene lowered serum MDA and tumor necrosis factor (TNF-α) levels and elevated liver GSH level (P < .001). Insulin resistance was higher in the rats fed HFD than in rats supplemented with lycopene. The data indicate that supplementation with lycopene can reduce high-fat diet-induced oxidative stress to the cells

Chromium picolinate and chromium histidinate protects against renal dysfunction by modulation of NF-κB pathway in high-fat diet fed and Streptozotocin-induced diabetic rats

<p>Abstract</p> <p>Background</p> <p>Diabetic nephropathy is one of major complications of diabetes mellitus. Although chromium is an essential element for carbohydrate and lipid metabolism, its effects on diabetic nephropathy are not well understood. The present study was conducted to investigate the effects of chromium picolinate (CrPic) and chromium histidinate (CrHis) on nuclear factor-kappa B (NF-κB) and nuclear factor-E2-related factor-2 (Nrf2) pathway in the rat kidney.</p> <p>Methods</p> <p>Male Wistar rats were divided into six groups. Group I received a standard diet (8% fat) and served as a control; Group II was fed with a standard diet and received CrPic; Group III was fed with a standard diet and received CrHis; Group IV received a high fat diet (HFD, 40% fat) for 2 weeks and then were injected with streptozotocin (STZ) (HFD/STZ); Group V was treated as group IV (HFD/STZ) but supplemented with CrPic for 12 weeks. Group VI was treated as group IV (HFD/STZ) but supplemented with CrHis.</p> <p>Results</p> <p>The increased NF-κβ p65 in the HFD/STZ group was inhibited by CrPic and CrHis supplementation (<it>P </it>< 0.05). In STZ-treated rats, a significant decrease in levels of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) was found in kidney tissues when compared to control rats (<it>P </it>< 0.05). A significant increase in the levels of IκBα was observed in CrPic- and CrHis-treated rats when compared with STZ-treated rats. Renal Nrf2 levels were significantly decreased in diabetic rats compared with the control rats. There was a higher tendency for increase of kidney Nrf2 level and decrease in kidney NFκBp65 levels and 4- hydroxyl nonenal (4-HNE) protein adducts (<it>P </it>< 0.05) in diabetic rats.</p> <p>Conclusion</p> <p>Our result show that in kidney tissue CrHis/CrPic increases Nrf2 level, parallelly decreases NF-κB and partially restores IκBα levels in HFD/STZ group, suggesting that CrPic and CrHis may play a role in antioxidant defense system via the Nrf2 pathway by reducing inflammation through NF-κβ p65 inhibition. Moreover, a greater reduction in NF-κB expression and greater increases in expressions of IκBα and Nrf2 in diabetic rats supplemented with CrHis than rats supplemented with CrPic suggest that CrHis has more favorable effects than CrPic.</p

Protective Role of Genistein in Acute Liver Damage Induced by Carbon Tetrachloride

Aim. In the present study, we investigated the protective effect of genistein in experimental acute liver damage induced by CCl4. Method. Forty rats were equally allocated to 5 groups. The first group was designated as the control group (group 1). The second group was injected with intraperitoneal CCl4 for 3 days (group 2). The third group was injected with subcutaneous 1 mg/kg genistein for 4 days starting one day before CCl4 injection. The fourth group was injected with intraperitoneal CCl4 for 7 days. The fifth group was injected with subcutaneous 1 mg/kg genistein for 8 days starting one day before CCl4 injection. Plasma and liver tissue malondialdehyde (MDA) and liver glutathione levels, as well as AST and ALT levels were studied. A histopathological examination was conducted. Results. Liver tissue MDA levels were found significantly lower in group 3, in comparison to group 2 (P < .05). Liver tissue MDA level in group 5 was significantly lower than that in group 4 (P < .001). Liver tissue glutathione levels were higher in group 5 and 3, relative to groups 4 and 2, respectively (P > .05 for each). Inflammation and focal necrosis decreased in group 3, in comparison to group 2 (P < .001 for each). Inflammation and focal necrosis in group 5 was lower than that in group 4 (P < .001). Actin expression decreased significantly in group 5, relative to group 4 (P < .05). Conclusion. Genistein has anti-inflammatory and antinecrotic effects on experimental liver damage caused by CCl4. Genistein reduces liver damage by preventing lipid peroxidation and strengthening antioxidant systems

The Protective Effects of a Combination of an Arginine Silicate Complex and Magnesium Biotinate Against UV-Induced Skin Damage in Rats

The purpose of this study was to observe the effects of a novel combination of inositol-stabilized arginine silicate complex (ASI) and magnesium biotinate (MgB) on the prevention of skin damage after UVB exposure in rats. Forty-nine Sprague-Dawley rats were randomized into one of the following groups: (1) NC, normal control, (2) SC, shaved control, (3) UVB (exposed to UVB radiation), (4) ASI+MgB-L (Low Dose), (5) ASI+MgB-H (High Dose), (6) ASI+MgB-L+MgB cream, (7) ASI+MgB-H+MgB cream. The results showed that ASI+MgB treatment alleviated the macroscopic and histopathological damages in the skin of rats caused by UVB exposure. Skin elasticity evaluation showed a similar trend. ASI+MgB increased serum Mg, Fe, Zn, Cu, Si, biotin, and arginine concentrations and skin hydroxyproline and biotinidase levels while decreasing skin elastase activity (p &lt; 0.05) and malondialdehyde (MDA) concentration (p &lt; 0.001). Moreover, ASI+MgB treatment increased skin levels of biotin-dependent carboxylases (ACC1, ACC2, PC, PCC, MCC) and decreased mammalian target of rapamycin (mTOR) pathways and matrix metalloproteinase protein levels by the regulation of the activator protein 1 (AP-1), and mitogen activated protein kinases (MAPKs) signaling pathways. In addition, ASI+MgB caused lower levels of inflammatory factors, including TNF-α, NFκB, IL-6, IL-8, and COX-2 in the skin samples (p &lt; 0.05). The levels of Bax and caspase-3 were increased, while anti-apoptotic protein Bcl-2 was decreased by UVB exposure, which was reversed by ASI+MgB treatment. These results show that treatment with ASI and MgB protects against skin damage by improving skin appearance, elasticity, inflammation, apoptosis, and overall health

Laying performance, digestibility and plasma hormones in laying hens exposed to chronic heat stress as affected by betaine, vitamin C, and/or vitamin E supplementation

Heat stress had a negative effect on laying hens' performance, thus this research was to study the influences of betaine (Bet, 1000 mg/kg betaine), vitamin C (VC, 200 mg/kg ascorbic acid), and vitamin E (VE, 150 mg/kg a-Tocopherol acetate) and their possible combinations on egg production, digestibility of nutrients, plasma hormones and reproductive organs of dual-purpose hens exposed to chronic heat stress. Two hundred and eighty eight hens and thirty-six cocks from 32 to 48 weeks of age were divided into nine treatment groups of four replicates, each containing eight hens and one cock. One group was kept under thermo-natural condition and the eight others were kept under chronic heat stress (CHS). One of these eight was used as a negative control, while the others were supplemented with VC, VE and/or betaine and their possible combinations. Body weights, laying rate, feed intake, and feed conversion ratio in hens reared under CHS rooster without any supplementation during 32 to 48 weeks of impairment (P = 0.0052) were recorded. Hens reared under heat stress and fed a diet supplemented with either Bet, VC, VE or combination of the supplements increased production traits. However, hens supplemented with VC showed the greatest production traits. Plasma glucose, estradiol-17 (E-2), progesterone (P-4), tri-iodothyronine (T-3) and thyroxine (T-4) decreased in hens reared under CHS and fed a diet with no supplementation compared to the other treatments (P = 0.001). Liver weights, spleen weights, thyroid gland weights, ovary weights, oviduct weights and oviduct lengths were lowest in hens reared under CHS and fed a diet with no supplementation (P = 0.0480). In conclusion, dual purpose hens reared under CHS and supplemented with VC at 200 mg/kg diet and Bet at 1000 mg/kg enhanced the laying performance and combated CHS

Nuclear Targeting of IGF-1 Receptor in Orbital Fibroblasts from Graves' Disease: Apparent Role of ADAM17

Insulin-like growth factor-1 receptor (IGF-1R) comprises two subunits, including a ligand binding domain on extra- cellular IGF-1Rα and a tyrosine phosphorylation site located on IGF-1Rβ. IGF-1R is over-expressed by orbital fibroblasts in the autoimmune syndrome, Graves' disease (GD). When activated by IGF-1 or GD-derived IgG (GD-IgG), these fibroblasts produce RANTES and IL-16, while those from healthy donors do not. We now report that IGF-1 and GD-IgG provoke IGF-1R accumulation in the cell nucleus of GD fibroblasts where it co-localizes with chromatin. Nuclear IGF-1R is detected with anti-IGF-1Rα-specific mAb and migrates to approximately 110 kDa, consistent with its identity as an IGF-1R fragment. Nuclear IGF-1R migrating as a 200 kDa protein and consistent with an intact receptor was undetectable when probed with either anti-IGF-1Rα or anti-IGF-1Rβ mAbs. Nuclear redistribution of IGF-1R is absent in control orbital fibroblasts. In GD fibroblasts, it can be abolished by an IGF-1R-blocking mAb, 1H7 and by physiological concentrations of glucocorticoids. When cell-surface IGF-1R is cross-linked with 125I IGF-1, 125I-IGF-1/IGF-1R complexes accumulate in the nuclei of GD fibroblasts. This requires active ADAM17, a membrane associated metalloproteinase, and the phosphorylation of IGF-1R. In contrast, virally encoded IGF-1Rα/GFP fusion protein localizes equivalently in nuclei in both control and GD fibroblasts. This result suggests that generation of IGF-1R fragments may limit the accumulation of nuclear IGF-1R. We thus identify a heretofore-unrecognized behavior of IGF-1R that appears limited to GD-derived fibroblasts. Nuclear IGF-1R may play a role in disease pathogenesis

Influence of dietary genistein and polyunsaturated fatty acids on lipid peroxidation and fatty acid composition of meat in quail exposed to heat stress.

This experiment was conducted to investigate the effects of polyunsaturated fatty acids (PUFA) and genistein on performance and meat fatty acid profiles in quail exposed to heat stress. A total of 360 Japanese quail were divided into 12 groups in a 2 x 2 x 3 factorial design; each group comprised 30 quail with five replicates and were kept either at 22 +/- 2 degrees C for 24 h/day (Thermoneutral, TN) or 34 +/- 2 degrees C for 8 h/day (08:00 to 17:00 h) followed by 22 degrees C for 16 h (heat stress, HS) conditions. The diet contained either two levels of PUFA at 15 or 45% of total fat or three levels of genistein at 0, 400, or 800 mg/kg. Bodyweight gain, feed intake, and feed efficiency were lower (p >= 0.01) for quail reared under heat stress and fed low PUFA. Increasing dietary genistein in a linear manner improved the productive performance (p = 0.006) with no regard to genistein supplementation. This study revealed that genistein with greater doses along with greater PUFA inclusion to the diet of quail reared under heat stress is recommended for alleviating adverse effects of heat stress and for yielding healthier meat for human consumption