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n-3 Polyunsaturated fatty acids alter benzo[a]pyrene metabolism and genotoxicity in human colon epithelial cell models.
Tylichová, Z, Neča, J, Topinka, J, Milcová, A, Hofmanová, J, Kozubík, A, Machala, M, Vondráček, J
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2019;:374-384
Abstract
Dietary carcinogens, such as benzo[a]pyrene (BaP), are suspected to contribute to colorectal cancer development. n-3 Polyunsaturated fatty acids (PUFAs) decrease colorectal cancer risk in individuals consuming diets rich in PUFAs. Here, we investigated the impact of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid on metabolism and genotoxicity of BaP in human cell models derived from the colon: HT-29 and HCT-116 cell lines. Both PUFAs reduced levels of excreted BaP metabolites, in particular BaP-tetrols and hydroxylated BaP metabolites, as well as formation of DNA adducts in HT-29 and HCT-116 cells. However, EPA appeared to be a more potent inhibitor of formation of some intracellular BaP metabolites, including BaP-7,8-dihydrodiol. EPA also reduced phosphorylation of histone H2AX (Ser139) in HT-29 cells, which indicated that it may reduce further forms of DNA damage, including DNA double strand breaks. Both PUFAs inhibited induction of CYP1 activity in colon cells determined as 7-ethoxyresorufin-O-deethylase (EROD); this was at least partly linked with inhibition of induction of CYP1A1, 1A2 and 1B1 mRNAs. The downregulation and/or inhibition of CYP1 enzymes by PUFAs could thus alter metabolism and reduce genotoxicity of BaP in human colon cells, which might contribute to known chemopreventive effects of PUFAs in colon epithelium.
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2.
Molecular mechanisms of curcumin and its analogs in colon cancer prevention and treatment.
Selvam, C, Prabu, SL, Jordan, BC, Purushothaman, Y, Umamaheswari, A, Hosseini Zare, MS, Thilagavathi, R
Life sciences. 2019;:117032
Abstract
Colorectal cancer remains to be the most prevalent malignancy in humans and 1.5 million men and women living in the United States are diagnosed with colorectal cancer, with a predicted 145,600 new cases to be diagnosed in 2019. Curcuminoids and its synthetic analogs are now of interest due to their bioactive attributes, especially their action as anticancer activity in various cancer cell line models. Several in vivo and in vitro studies have substantially proved their anticancer activities against colon cancer cell lines. Curcumin analogues like IND-4, FLLL, GO-Y030 and C086 have demonstrated to produce greater cytotoxicity when experimentally studied and study results from many have been suggested to be the same. Combination of curcumin with therapeutic cancer agents like tolfenamic acid, 5-fluorouracil, resveratrol and dasatinib showed improved cytotoxicity and chemotherapeutic effect. The results propose that employment of curcumin with novel drug delivery systems like liposome, micelles and nanoparticle have been performed which could improve the therapeutic efficacy against colon cancer. The present review highlights the mechanism of action, synergistic effect and novel delivery methods to improve the therapeutic potential of curcumin.
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Molecular Mechanisms Underlying Cancer Preventive and Therapeutic Potential of Algal Polysaccharides.
Sajadimajd, S, Momtaz, S, Haratipour, P, El-Senduny, FF, Panah, AI, Navabi, J, Soheilikhah, Z, Farzaei, MH, Rahimi, R
Current pharmaceutical design. 2019;(11):1210-1235
Abstract
BACKGROUND Algal polysaccharide and oligosaccharide derivatives have been shown to possess a variety of therapeutic potentials and drug delivery applications. Algal polysaccharides contain sulfated sugar monomers derived from seaweed including brown, red, and green microalgae. Here, in this review, the recent progress of algal polysaccharides' therapeutic applications as anticancer agents, as well as underlying cellular and molecular mechanisms was investigated. Moreover, recent progress in the structural chemistry of important polysaccharides with anticancer activities were illustrated. METHODS Electronic databases including "Scopus", "PubMed", and "Cochrane library" were searched using the keywords "cancer", or "tumor", or "malignancy" in title/abstract, along with "algae", or "algal" in the whole text until July 2018. Only English language papers were included. RESULTS The most common polysaccharides involved in cancer management were sulfated polysaccharides, Fucoidans, Carageenans, and Ulvan from different species of algae that have been recognized in vitro and in vivo. The underlying anticancer mechanisms of algal polysaccharides included induction of apoptosis, cell cycle arrest, modulation of transduction signaling pathways, suppression of migration and angiogenesis, as well as activation of immune responses and antioxidant system. VEGF/VEGFR2, TGFR/Smad/Snail, TLR4/ROS/ER, CXCL12/ CXCR4, TGFR/Smad7/Smurf2, PI3K/AKT/mTOR, PBK/TOPK, and β-catenin/Wnt are among the main cellular signaling pathways which have a key role in the preventive and therapeutic effects of algal polysaccharides against oncogenesis. CONCLUSION Algal polysaccharides play a crucial role in the management of cancer and may be considered the next frontier in pharmaceutical research. Further well-designed clinical trials are mandatory to evaluate the efficacy and safety of algal polysaccharides in patients with cancer.
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Mechanisms of action of vitamin D in colon cancer.
Ferrer-Mayorga, G, Larriba, MJ, Crespo, P, Muñoz, A
The Journal of steroid biochemistry and molecular biology. 2019;:1-6
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Abstract
Colorectal cancer (CRC) is the neoplasia that is most frequently associated with vitamin D deficiency in epidemiological and observational studies in terms of incidence and mortality. Many mechanistic studies show that the active vitamin D metabolite (1α,25-dihydroxyvitamin D3 or calcitriol) inhibits proliferation and promotes epithelial differentiation of human colon carcinoma cell lines that express vitamin D receptor (VDR) via the regulation of a high number of genes. A key action underlining this effect is the multilevel inhibition of the Wnt/β-catenin signaling pathway, whose abnormal activation in colon epithelial cells initiates and promotes CRC. Recently, our group has shown that calcitriol modulates gene expression and inhibits protumoral properties of patient-derived colon cancer-associated fibroblasts (CAFs). Accordingly, high VDR expression in tumor stromal fibroblasts is associated with longer survival of CRC patients. Moreover, many types of immune cells express VDR and are regulated by calcitriol, which probably contributes to its action against CRC. Given the role attributed to the intestinal microbiota in CRC and the finding that it is altered by vitamin D deficiency, an indirect antitumoral effect of calcitriol is also plausible at this level. In summary, calcitriol has an array of potential protective effects against CRC by acting on carcinoma cells, CAFs, immune cells and probably also the gut microbiota.
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Resveratrol and other dietary polyphenols are inhibitors of estrogen metabolism in human breast cancer cells.
Poschner, S, Maier-Salamon, A, Thalhammer, T, Jäger, W
The Journal of steroid biochemistry and molecular biology. 2019;:11-18
Abstract
Polyphenols in foods and dietary supplements are commonly used for the prevention and treatment of a variety of malignancies, including breast cancer. However, daily intake by patients with breast cancer is controversial, as these compounds may stimulate cancer growth. Estrogens serve key roles in breast cancer cell proliferation; therefore, understanding the interaction between endogenous steroid hormones and natural dietary polyphenols is essential. Currently, comprehensive knowledge regarding these effects remains limited. The current review summarizes the dose-dependent in vitro and in vivo interactions of resveratrol and other dietary polyphenols with estrogen precursors, active estrogens, catechol estrogens and their respective glucuronidated, sulfated, glutathionated or O-methylated metabolites in estrogen receptor alpha negative (ERα-) and positive (ERα+) breast cancer. Which estrogen-metabolizing enzymes are affected by polyphenols is also reviewed in detail. Furthermore, the impacts of dose and therapy duration on disease development and progression in patients with breast cancer are discussed. The present article is part of a Special Issue titled 'CSR 2018'.
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Dietary Compounds for Targeting Prostate Cancer.
Noh, S, Choi, E, Hwang, CH, Jung, JH, Kim, SH, Kim, B
Nutrients. 2019;(10)
Abstract
Prostate cancer is the third most common cancer worldwide, and the burden of the disease is increased. Although several chemotherapies have been used, concerns about the side effects have been raised, and development of alternative therapy is inevitable. The purpose of this study is to prove the efficacy of dietary substances as a source of anti-tumor drugs by identifying their carcinostatic activities in specific pathological mechanisms. According to numerous studies, dietary substances were effective through following five mechanisms; apoptosis, anti-angiogenesis, anti-metastasis, microRNA (miRNA) regulation, and anti-multi-drug-resistance (MDR). About seventy dietary substances showed the anti-prostate cancer activities. Most of the substances induced the apoptosis, especially acting on the mechanism of caspase and poly adenosine diphosphate ribose polymerase (PARP) cleavage. These findings support that dietary compounds have potential to be used as anticancer agents as both food supplements and direct clinical drugs.
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Genistein reduces proliferation of EP3-expressing melanoma cells through inhibition of PGE2-induced IL-8 expression.
Venza, I, Visalli, M, Oteri, R, Beninati, C, Teti, D, Venza, M
International immunopharmacology. 2018;:86-95
Abstract
Genistein, a natural isoflavone found in soybean products, is considered as a powerful anti-cancer agent, although the involved mechanisms are not fully understood. There is a growing body of evidence that, among the genes inhibited by genistein and responsible for cell cycle progression, invasion, metastasis, and angiogenesis, IL-8 occupies a relevant place. On the other hand, it is equally well documented that IL-8 is upregulated by prostaglandin E2 (PGE2) in different pathological conditions, particularly in neoplastic disease. Here we investigated whether genistein could affect cell growth in a panel of oral, uveal and cutaneous melanoma cell lines by interfering with basal or PGE2-induced IL-8 production. To this end, experiments were performed to evaluate the effect of PGE2 treatment on IL-8 levels, the expression and the role of PGE2 receptors and whether genistein could be able to interfere with these events. Finally, it was evaluated whether the inhibition of oral, uveal and cutaneous melanoma cell proliferation in the presence of genistein could be related to a reduction of IL-8 levels. We show that PGE2 enhances IL-8 synthesis via the EP3 receptor and that genistein is able to down-regulate the latter, as well as to decrease IL-8 mRNA and protein expression, thereby inhibiting oral, uveal and cutaneous melanoma cell proliferation. Taken together, our data provide new insights into the anti-cancer properties of genistein by showing that this flavonoid may affect the development and growth of melanoma at oral, uveal and cutaneous sites. Moreover, these results provide evidence that genistein may exert its therapeutic activity through its ability to prevent PGE2-mediated IL-8 induction.
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Differences in risk factor-colorectal adenoma associations according to non-steroidal anti-inflammatory drug use.
Mujtaba, S, Bostick, RM
European journal of gastroenterology & hepatology. 2018;(11):1318-1326
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Abstract
OBJECTIVE Because multiple observational studies and large, randomized controlled trials indicate that NSAIDs strongly reduce the risk of colorectal neoplasms, we investigated whether NSAID use masks associations of various other risk factors with colorectal neoplasms. MATERIALS AND METHODS Using pooled data from three case-control studies of incident, sporadic colorectal adenoma (pooled n=789 cases, 2035 polyp-free controls), using multivariable logistic regression, we investigated various risk factor-colorectal adenoma associations stratified by NSAID use. RESULTS Example multivariable-adjusted odds ratios [95% confidence intervals (CI)] for those in the highest relative to the lowest quartiles of exposure, by regular nonaspirin NSAID nonuse/use, respectively, were 1.57 (95% CI: 0.96-2.55) versus 1.14 (95% CI: 0.37, 3.49) for total fat, 1.37 (95% CI: 0.86-2.18) versus 0.70 (95% CI: 0.23-2.25) for saturated fat, 0.93 (95% CI: 0.68-1.28) versus 1.30 (95% CI: 0.61-2.75) for calcium, 0.89 (95% CI: 0.64-1.23) versus 1.38 (95% CI: 0.65-2.94) for total fruits and vegetables, and 0.85 (95% CI: 0.65-1.11) versus 0.94 (95% CI: 0.52-1.71) for physical activity. For current versus never smokers, the odds ratios (95% CIs) among regular non-NSAID users/nonusers were 2.91 (95% CI: 2.22-3.82) versus 1.75 (95% CI: 0.90-3.41), respectively, and for those who were obese versus those who were normal weight, they were 1.67 (95% CI: 1.28-2.17) versus 1.19 (95% CI: 0.69-2.04), respectively. CONCLUSION Our findings suggest that regular nonaspirin NSAID use may mask, beyond simple confounding, associations of major risk factors with colorectal adenoma, and support routinely assessing such associations stratified by regular nonaspirin NSAID use.
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[Efficacy of lycopene intake in primary prevention of prostate cancer: a systematic review of the literature and meta-analysis.].
Cataño, JG, Trujillo, CG, Caicedo, JI, Bravo-Balado, A, Robledo, D, Mariño-Alvarez, AM, Pedraza, A, Arcila, MJ, Plata, M
Archivos espanoles de urologia. 2018;(2):187-197
Abstract
OBJECTIVE To evaluate the efficacy of lycopene intake in primary prevention of prostate cancer (PCa). METHODS A systematic search of the literature was conducted in March 2015 and the articles published between the years 1990-2015 were reviewed. The following search terms were used: prostate cancer, prostatic neoplasm, lycopene, prevention, effectiveness and efficacy (MeSH). Publications including research in humans, written in English and whose texts were accessible were reviewed. The types of studies included were: clinical trials, cohort and case-control studies. We found 343 articles; of these, 27 were included in the systematic review. After the latter were rigorously analyzed, 23 were included in the meta-analysis using the pooled odds ratios (OR) and risk ratios (RR) of case-control and cohort studies, respectively, and their confidence intervals (95% CI), using random-effects models with Review Manager 5.2. RESULTS Out of the 27 articles included in the systematic review, 22 were case-control and 5 were cohort studies. For the case-control studies, the total number of patients with PCa was 13,999 and the total number of controls 22,028. Cohort studies included 187,417 patients and PCa was diagnosed in 8,619 of these. The metaanalysis determined an OR = 0.94 (IC 95% 0.89-1.00) and RR = 0.9 (IC 95% 0.85-0.95) of PCa related with lycopene and/or raw or cooked tomatoes intake. CONCLUSIONS Although our study found that there is a statistically significant inverse association between lycopene intake and PCa, the magnitude of this association is weak and comes solely from observational studies, which do not allow recommending its use as a standard of practice. High-quality randomized clinical trials are required to clarify current evidence.
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Anticarcinogenic activities of sulforaphane are influenced by Nerve Growth Factor in human melanoma A375 cells.
Arcidiacono, P, Stabile, AM, Ragonese, F, Pistilli, A, Calvieri, S, Bottoni, U, Crisanti, A, Spaccapelo, R, Rende, M
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2018;:154-161
Abstract
Melanoma is a severe form of cancer, resistant to conventional therapies. According to in vitro studies, sulforaphane, a dietary component, has been considered a promising antineoplastic candidate. The present study analyzes the in vitro biological effects of sulforaphane in A375 melanoma cell line with or without the addition of Nerve Growth Factor. For the first time, our results show that a supplementation of Nerve Growth Factor partially reverses the sulforaphane-induced: i) inhibition of cell migration, ii) pro apoptotic changes in cell cycle and iii) modulation of active caspase-3. Furthermore, we report the sulforaphane-induced modulation in the expression of Nerve Growth Factor receptors TrKA and p75NTR, shifting their ratio from pro survival to pro apoptotic. In conclusion, the present study evidences that in vivo the antineoplastic effects of sulforaphane may be reduced by the contemporaneous presence of other biological elements such as Nerve Growth Factor and it contributes to a better definition of the real in vivo potentiality of sulforaphane as antineoplastic candidate.