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1.
Anti-Cancer Activity of Phytochemicals Targeting Hypoxia-Inducible Factor-1 Alpha.
Yun, BD, Son, SW, Choi, SY, Kuh, HJ, Oh, TJ, Park, JK
International journal of molecular sciences. 2021;(18)
Abstract
Hypoxia-inducible factor-1 alpha (HIF-1α) is overexpressed in cancer, leading to a poor prognosis in patients. Diverse cellular factors are able to regulate HIF-1α expression in hypoxia and even in non-hypoxic conditions, affecting its progression and malignant characteristics by regulating the expression of the HIF-1α target genes that are involved in cell survival, angiogenesis, metabolism, therapeutic resistance, et cetera. Numerous studies have exhibited the anti-cancer effect of HIF-1α inhibition itself and the augmentation of anti-cancer treatment efficacy by interfering with HIF-1α-mediated signaling. The anti-cancer effect of plant-derived phytochemicals has been evaluated, and they have been found to possess significant therapeutic potentials against numerous cancer types. A better understanding of phytochemicals is indispensable for establishing advanced strategies for cancer therapy. This article reviews the anti-cancer effect of phytochemicals in connection with HIF-1α regulation.
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2.
(‒)-Cannabidiolic Acid, a Still Overlooked Bioactive Compound: An Introductory Review and Preliminary Research.
Formato, M, Crescente, G, Scognamiglio, M, Fiorentino, A, Pecoraro, MT, Piccolella, S, Catauro, M, Pacifico, S
Molecules (Basel, Switzerland). 2020;(11)
Abstract
Cannabidiolic acid (CBDA) is the main phytocannabinoid in fiber and seed-oil hemp (Cannabis sativa L.) plants, but its potential health-related capabilities have been masked for years by a greater scientific interest towards its neutral derivative cannabidiol (CBD). This review aims to collect from the literature and critically discuss all the information about this molecule, starting from its biosynthesis, and focusing on its bioactivity, as an anti-inflammatory, anti-emetic, anti-convulsant, and anti-cancerogenic drug. Furthermore, in the awareness that, despite its multiple bioactive effects, currently poor efforts have been made to achieve its reliable purification, herein, we propose a relatively simple, fast, and inexpensive procedure for its recovery from pollen of industrial hemp cultivars. Spectroscopic and spectrometric techniques allowed us to unequivocally identify pure isolated CBDA and to distinguish it from the constitutional isomer tetrahydrocannabinolic acid (THCA-A).
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3.
Leukoplakia and Immunology: New Chemoprevention Landscapes?
Grigolato, R, Bizzoca, ME, Calabrese, L, Leuci, S, Mignogna, MD, Lo Muzio, L
International journal of molecular sciences. 2020;(18)
Abstract
Oral potentially malignant disorders (OPMDs) comprise a range of clinical-pathological alterations frequently characterized by an architectural and cytological derangements upon histological analysis. Among them, oral leukoplakia is the most common type of these disorders. This work aims to analyze the possible use of drugs such as immunochemopreventive agents for OPMDs. Chemoprevention is the use of synthetic or natural compounds for the reversal, suppression, or prevention of a premalignant lesion conversion to malignant form. Experimental and in vivo data offer us the promise of molecular prevention through immunomodulation; however, currently, there is no evidence for the efficacy of these drugs in the chemoprevention action. Alternative ways to deliver drugs, combined use of molecules with complementary antitumor activities, diet influence, and better definition of individual risk factors must also be considered to reduce toxicity, improve compliance to the protocol treatment and offer a better individualized prevention. In addition, we must carefully reconsider the mode of action of many traditional cancer chemoprevention agents on the immune system, such as enhancing immunosurveillance and reversing the immune evasion. Several studies emphasize the concept of green chemoprevention as an alternative approach to accent healthy lifestyle changes in order to decrease the incidence of HNSCC.
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4.
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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5.
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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6.
[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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Soy Consumption and the Risk of Prostate Cancer: An Updated Systematic Review and Meta-Analysis.
Applegate, CC, Rowles, JL, Ranard, KM, Jeon, S, Erdman, JW
Nutrients. 2018;(1)
Abstract
Prostate cancer (PCa) is the second most commonly diagnosed cancer in men, accounting for 15% of all cancers in men worldwide. Asian populations consume soy foods as part of a regular diet, which may contribute to the lower PCa incidence observed in these countries. This meta-analysis provides a comprehensive updated analysis that builds on previously published meta-analyses, demonstrating that soy foods and their isoflavones (genistein and daidzein) are associated with a lower risk of prostate carcinogenesis. Thirty articles were included for analysis of the potential impacts of soy food intake, isoflavone intake, and circulating isoflavone levels, on both primary and advanced PCa. Total soy food (p < 0.001), genistein (p = 0.008), daidzein (p = 0.018), and unfermented soy food (p < 0.001) intakes were significantly associated with a reduced risk of PCa. Fermented soy food intake, total isoflavone intake, and circulating isoflavones were not associated with PCa risk. Neither soy food intake nor circulating isoflavones were associated with advanced PCa risk, although very few studies currently exist to examine potential associations. Combined, this evidence from observational studies shows a statistically significant association between soy consumption and decreased PCa risk. Further studies are required to support soy consumption as a prophylactic dietary approach to reduce PCa carcinogenesis.
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Chemoprevention and Treatment of Pancreatic Cancer: Update and Review of the Literature.
Benzel, J, Fendrich, V
Digestion. 2018;(4):275-287
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma is one of the most lethal types of cancer with a 5-year survival rate of around 7%. Due to the relatively poor prognosis, the potential need of an effective chemoprevention is highly needed. SUMMARY Different risk factors like smoking or hereditary tumour syndromes should be known for early detection of pancreatic intraepithelial neoplasia. Chemopreventive dietary agents include curcumin, capsaicin and flavonoid, whereas potential chemopreventive drugs compromise aspirin, metformin or statins. This review aims to give an overview on potential risk factors for the development of pancreatic cancer. Furthermore, we try to summarise known chemopreventive agents to support the fight against this lethal disease. Key Messages: On the one hand, there are natural agents that exhibit preventive properties and can lead to the prohibition of pancreatic cancer. On the other hand, there are drugs and agents that are currently used in other contexts and are thus already approved and studied in terms of their mechanisms of effects and the related secondary effects.
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9.
Melanoma Chemoprevention: Current Status and Future Prospects.
Chhabra, G, Ndiaye, MA, Garcia-Peterson, LM, Ahmad, N
Photochemistry and photobiology. 2017;(4):975-989
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Abstract
The incidence of skin cancers, both nonmelanoma and melanoma, is increasing in the United States. The ultraviolet radiation, mainly from sun, is considered the major cause for these neoplasms. While nonmelanoma skin cancers are far more numerous, melanoma remains the most challenging. This is because melanoma can become extremely aggressive and its incidence is increasing worldwide due to lack of effective early detection, as well as disease recurrence, following both surgery and chemotherapy. Therefore, in addition to better treatment options, newer means are required to prevent melanomas from developing. Chemoprevention is a reasonable cost-effective approach to prevent carcinogenesis by inhibiting the processes of tumor initiation, promotion and progression. Melanoma is a progressive disease, which makes it very suitable for chemopreventive interventions, by targeting the processes and molecular pathways involved in the progression of melanoma. This review discusses the roles of various chemopreventive agents such as NSAIDs, statins, vitamins and dietary agents in melanoma and highlights current advancements and our perspective on future of melanoma chemoprevention. Although considerable preclinical data suggest that melanoma may be prevented or delayed by a numerous chemopreventive agents, we realize there are insufficient clinical studies evaluating their efficacy and long-term safety for human use.
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10.
Cellular and Molecular Targets of Resveratrol on Lymphoma and Leukemia Cells.
Frazzi, R, Guardi, M
Molecules (Basel, Switzerland). 2017;(6)
Abstract
Resveratrol (RSV) is a well known chemopreventive molecule featuring anti-cancer properties. Our paper describes the main molecular targets of RSV linked to its antiproliferative activity on lymphoma and leukemia experimental models. It discusses further the most recent and most promising among these molecular targets for a translational application.