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Cancer Chemoprevention: A Strategic Approach Using Phytochemicals.

Cancer chemoprevention approaches are aimed at preventing, delaying, or suppressing tumor incidence using synthetic or natural bioactive agents. Mechanistically, chemopreventive agents also aid in mitigating cancer development, either by impeding DNA damage or by blocking the division of premalignant cells with DNA damage. Several pre-clinical studies have substantiated the benefits of using various dietary components as chemopreventives in cancer therapy. The incessant rise in the number of cancer cases globally is an issue of major concern. The excessive toxicity and chemoresistance associat

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… | Mutagen | Head and neck cancer, Cancers of urogenital tract | ( Cai et al., 2018 , Sabatini and Chiocca 2020 ) Hepatitis B virus | Mutagen | Liver Cancer | MacLachlan et al. (2015) Asbestos | Mutagen | Pleural Mesothelioma | Tossavainen (2004) Alcohol | Dietary factor | Breast cancer, liver cancer … Studies on the effect of resveratrol on three mutagens namely, aflatoxin B1, 2-amino-3-methylimidazo (4,5-f) quinoline and N-nitroso-N-methyl urea have established that resveratrol significantly decreased the mutagenicity of all three mutagens ( Langová et al., 2005 ). …

Genetic Variants That Predispose to DNA Double-Strand Breaks in Lymphocytes From a Subset of Patients With Familial Colorectal Carcinomas.

BACKGROUND & AIMS: DNA structural lesions are prevalent in sporadic colorectal cancer. Therefore, we proposed that gene variants that predispose to DNA double-strand breaks (DSBs) would be found in patients with familial colorectal carcinomas of an undefined genetic basis (UFCRC). METHODS: We collected primary T cells from 25 patients with UFCRC and matched patients without colorectal cancer (controls) and assayed for DSBs. We performed exome sequence analyses of germline DNA from 20 patients with UFCRC and 5 undiagnosed patients with polyposis. The prevalence of identified variants in genes

A novel Phex mutation in a new mouse model of hypophosphatemic rickets.

X-linked hypophosphatemic rickets (XLH) is a dominantly inherited disease characterized by renal phosphate wasting, aberrant vitamin D metabolism, and defective bone mineralization. It is known that XLH in humans and in certain mouse models is caused by inactivating mutations in PHEX/Phex (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). By a genome-wide N-ethyl-N-nitrosourea (ENU)-induced mutagenesis screen in mice, we identified a dominant mouse mutation that exhibits the classic clinical manifestations of XLH, including growth retardation, skeletal abnormali

Computational study of SENP1 in cancer by novel natural compounds and ZINC database screening.

Introduction: Sentrin-specific protease 1 (SENP1) is a protein whose main function is deSUMOylation. SENP1 inhibits apoptosis, and increases angiogenesis, estrogen and androgen receptor transcription and c-Jun transcription factor, proliferation, growth, cell migration, and invasion of cancer. The in vivo and in vitro studies also demonstrated which natural compounds, especially phytochemicals, minerals, and vitamins, prevent cancer. More than 3,000 plant species have been reported in modern medicine. Natural compounds have many anti-cancerous andanti-turmeric properties such as antioxidative,

Final report on the safety assessment of octoxynol-1, octoxynol-3, octoxynol-5, octoxynol-6, octoxynol-7, octoxynol-8, octoxynol-9, octoxynol-10, octoxynol-11, octoxynol-12, octoxynol-13, octoxynol-16, octoxynol-20, octoxynol-25, octoxynol-30, octoxynol-33, octoxynol-40, octoxynol-70, octoxynol-9 carboxylic acid, octoxynol-20 carboxylic acid, potassium octoxynol-12 phosphate, sodium octoxynol-2 ethane sulfonate, sodium octoxynol-2 sulfate, sodium octoxynol-6 sulfate, and sodium octoxynol-9 sulfate.

Octoxynols are ethoxylated alkylphenols in which the size of the molecule is related to the number of moles of ethylene oxide used in synthesis. Reactions are performed at elevated temperature, under pressure, and in the presence of NaOH. It is possible that the synthesis may leave trace amounts of ethylene oxide, 1,4-dioxane, and unreacted C9 phenols. Octoxynols of various chain lengths as well as octoxynol salts and organic acids function in cosmetics either as surfactants--emulsifying agents, surfactants--cleansing agents, surfactant--solubilizing agents, or surfactants--hydrotropes in a wi

NTP Toxicology and Carcinogenesis Studies of Chlorinated Paraffins (C23, 43% Chlorine) (CAS No. 108171-27-3) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Toxicology and carcinogenesis studies of chlorinated paraffins (C23, 43% chlorine), an extreme-pressure lubricant and flame retardant, were conducted by administering the chemical in corn oil by gavage to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex, 5 days per week for 103 weeks. Additional groups of 10 rats per sex and dose were examined at 6 and at 12 months. Male rats received doses of 0, 1,875, or 3,750 mg/kg body weight; female rats were given 0, 100, 300, or 900 mg/kg. Male and female mice received 0, 2,500, or 5,000 mg/kg. Doses selected for the 2-year studies were based on

Final report on the safety assessment of methoxyisopropanol and methoxyisopropyl acetate as used in cosmetics.

Methoxyisopropanol and Methoxyisopropyl Acetate, commonly known as propylene glycol monomethyl ether (PGME) and propylene glycol monomethyl ether acetate (PGMEA), respectively, have fragrance, solvent, and viscosity-decreasing functions in cosmetics, although only Methoxyisopropanol is in current use at concentrations ranging from 4% to 35%. Methoxyisopropanol is easily absorbed into the bloodstream upon inhalation or ingestion. The acetate ester is readily metabolized to Methoxyisopropanol in the body, which is excreted unchanged in the expired breath or in the urine as free or conjugated Met

NTP Toxicology and Carcinogenesis Studies of Isoprene (CAS No. 78-79-5) in F344/N Rats (Inhalation Studies).

Isoprene, the monomeric unit of natural rubber and naturally occurring terpenes and steroids, is primarily obtained as a by-product of naphtha cracking for ethylene production. It is emitted from plants and trees, has been detected in tobacco smoke and automobile exhaust, and was identified as a major endogenous hydrocarbon in human breath. Isoprene was selected for toxicologic evaluation because of its structural similarity to 1,3-butadiene, a potent, multi-organ, rodent carcinogen, and the potential for human exposure due to its large annual production volume. A previous 26-week inhalation s

NTP Toxicology and Carcinogenesis Studies of Acetaminophen (CAS No. 103-90-2) in F344 Rats and B6C3F1 Mice (Feed Studies).

Acetaminophen is a widely consumed analgesic found in several nonprescription pharmaceuticals. Toxicology and carcinogenesis studies were conducted by administering acetaminophen (purity >99%) in feed to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary cells. 14-DAY STUDIES: Rats were fed diets containing 0, 800, 1,600, 3,100, 6,200, or 12,500 ppm acetaminophen, and mice were fed diets containing 0, 250, 500, 1,000, 2,000, or 4,000 ppm acetaminophen. There were no

Molecular mechanisms of the preventable causes of cancer in the United States.

Annually, there are 1.6 million new cases of cancer and nearly 600,000 cancer deaths in the United States alone. The public health burden associated with these numbers has motivated enormous research efforts into understanding the root causes of cancer. These efforts have led to the recognition that between 40% and 45% of cancers are associated with preventable risk factors and, importantly, have identified specific molecular mechanisms by which these exposures modify human physiology to induce or promote cancer. The increasingly refined knowledge of these mechanisms, which we summarize here,

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… Alternatively, the mutational changes can be extrinsic, (i.e., caused by external carcinogens that are mutagenic). … While many carcinogens are mutagens, some of these mutagens are rapidly detoxified in the body; conversely, some nonmutagenic substances are converted to mutagens. …

The Role of Myrrh Metabolites in Cancer, Inflammation, and Wound Healing: Prospects for a Multi-Targeted Drug Therapy.

BackgroundMyrrh extract is a well-known medicinal plant with significant therapeutic benefits attributed to the activity of its diverse metabolites. It has promising activity against cancer and inflammatory diseases, and could serve as a potential therapeutic alternative since most therapeutic agents have severe side effects that impair quality of life.MethodThe current study identified the active metabolites from the myrrh resin methanolic extract. Then, the extracts were tested for in vitro anti-inflammatory and anti-cancer activity using cancer cell lines and Tamm-Horsfall Protein 1 (Thp-1)

Chemopreventive Potential of Caryophyllane Sesquiterpenes: An Overview of Preliminary Evidence.

Chemoprevention is referred to as a strategy to inhibit, suppress, or reverse tumor development and progression in healthy people along with high-risk subjects and oncologic patients through using pharmacological or natural substances. Numerous phytochemicals have been widely described in the literature to possess chemopreventive properties, although their clinical usefulness remains to be defined. Among them, caryophyllane sesquiterpenes are natural compounds widely occurring in nature kingdoms, especially in plants, fungi, and marine environments. Several structures, characterized by a commo

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… In these conditions, β-caryophyllene oxide exhibited the higher antimutagenic potency in reversing the CSC mutagenicity. … Particularly, their ability to counteract the mutagenicity of cigarette butt and condensed smoke has been partly ascribed to a possible enzyme inhibition, being the mutagens activated in the presence of the metabolic activator S9 [ 161 , 174 ]. …

Global ethylene oxide uses in foods and considerations for food safety.

Ethylene oxide (EtO) is a sterilant widely used for medical devices, but its use is controversial due to its carcinogenicity. In some countries, EtO is also used to fumigate food to eliminate foodborne pathogens, though this practice is banned in others. National regulations on EtO use in food vary widely; exporting countries prioritize trade facilitation and prevention of foodborne illness, while importing countries emphasize maintaining food safety and promoting domestic public health. These divergent public health priorities present challenges to establishing universal maximum residue limit

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Biphosphonates-associated osteonecrosis of the jaw: the role of gene-environment interaction.

Biphosphonate (BPN) are widely used in clinics to treat metastatic cancer and osteoporosis thus representing a problem not only for patients but also for workers involved in their preparation and administration. A similar exposure occurred years ago in match-making workers undergoing bone alterations similar to those consequent to BPN exposure. Osteonecrosis of the jaw (ONJ) is a main adverse effect related to BPN administration, which is performed in millions of patients worldwide for osteoporosis and cancer therapy, thus representing an emerging problem in public health. In susceptible patie

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… Environmental mutagens and oral osteonecrosis Bisphosphonates and DNA damage BPNs realize their antiosteoclast effects through modification of the Rho family GTPases, which include Rac GTPases [ 37 ]. … Both compounds induced a two-fold increase in his+ revertants in S. typhimurium TA1535 following metabolic activation with subcellular liver fractions, thus demonstrating the mutagenic attitude of BPNs. …

Does childhood obesity foreshadow a future time-bomb of early and more aggressive cancers?

There has been a global explosion in the prevalence of childhood obesity with 20% of children worldwide now growing up with excess weight and, despite many calls for interventions to redress the costs to health and society, rates continue to rise. It has also recently been observed that there is a global trend with the incidence of early-onset cancers, diagnoses prior to age 50, increasing. We outline the different lines of evidence implicating that these two trends may be linked. Conclusive proof will only be obtained when longitudinal studies, initiated after the current surge in childhood o

NTP Toxicology and Carcinogenesis Studies of Technical Grade Sodium Xylenesulfonate (CAS No. 1300-72-7) in F344/N Rats and B6C3F1 Mice (Dermal Studies).

Sodium xylenesulfonate is used as a hydrotrope, an organic compound that increases the ability of water to dissolve other molecules. Sodium xylenesulfonate is a component in a variety of widely used shampoos and liquid household detergents where it can constitute up to 10% of the total solution. Because of its widespread use, the potential for human exposure to sodium xylenesulfonate is great. Male and female F344/N rats and B6C3F1 mice were administered sodium xylenesulfonate in water or 50% ethanol dermally for 17 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmo

Chemical Patterns of Proteasome Inhibitors: Lessons Learned from Two Decades of Drug Design.

Drug discovery now faces a new challenge, where the availability of experimental data is no longer the limiting step, and instead, making sense of the data has gained a new level of importance, propelled by the extensive incorporation of cheminformatics and bioinformatics methodologies into the drug discovery and development pipeline. These enable, for example, the inference of structure-activity relationships that can be useful in the discovery of new drug candidates. One of the therapeutic applications that could benefit from this type of data mining is proteasome inhibition, given that mult

Oxyphenbutazone ameliorates carfilzomib induced cardiotoxicity in rats via inhibition of oxidative free radical burst and NF-κB/IκB-α pathway.

Carfilzomib (CFZ), a chemotherapeutic agent used for multiple myeloma treatments reported to cause high incidence of cardiac events either new onset and/or exacerbate formerly diagnosed heart failure with ventricular and myocardial dysfunction. Purpose: Current research designed to explore and examine the preventive effect of oxyphenbutazone in the CFZ -instigated cardiotoxicity. Methodology: Female Wistar Rats weighing 200-250 g selected randomly and grouped as follows: Group 1 designated as the Normal control and receive normal saline only. Group 2 served toxic control and exposed to CFZ (4

APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression.

Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) DNA cytosine deaminase 3B (A3B) is a DNA editing enzyme which induces genomic DNA mutations in multiple myeloma and in various other cancers. APOBEC family proteins are highly homologous so it is especially difficult to investigate the biology of specifically A3B in cancer cells. To easily and comprehensively investigate A3B function in myeloma cells, we used CRISPR/Cas9 to generate A3B reporter cells that contain 3×FLAG tag and IRES-EGFP sequences integrated at the end of the A3B gene. These reporter cells stably express

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… A3 proteins were originally identified as factors of the innate immunity due to their mutagenic activity on viral genomes, and have recently joined the growing list of key intrinsic mutagens that play a part in oncogenesis [ 1 ]. … APOBEC Enzymes: Mutagenic Fuel for Cancer Evolution and Heterogeneity . Cancer Discov . 2015 ; 5 ( 7 ): 704 – 12 . 10.1158/2159-8290.CD-15-0344 26091828 PMC4497973 4 Gao J , Choudhry H , Cao W . …