Phytochemical Regulation of UDP-Glucuronosyltransferases: Implications for Cancer Prevention

Saracino, Misty; Lampe, Johanna W.

doi:10.1080/01635580701458178

Cited by 41 publications

(28 citation statements)

References 296 publications

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“…of disease (Vincent et al, 2010;Mirmiran et al, 2012). Despite the protective effects of whole plant foods against the risk of breast cancer remain unclear (Nicodemus at al., 2001;Egeberg et al, 2009Masala at al., 2012, in the recent years, there have been growing evidences that phytochemicals and natural bioactive components in plant foods could have preventive effects in the incidence and development of different type of cancers (Loo et al, 2003;Saracino et al, 2007); moreover there is new approach to phytochemicals as standard complementary treatment of cancers (Sak et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Dietary Phytochemical Index and the Risk of Breast Cancer: A Case Control Study in a Population of Iranian Women

Bahadoran

Karimi²,

Houshiarrad³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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In this study we assessed the dietary phytochemical index in relation to the risk of breast cancer in women. This case-control study was conducted on 100 incident breast cancer cases and 175 healthy controls. Data regarding socio-demographic factors, medical history, medications, and anthropometric measurements were collected. Dietary data were obtained using a validated food frequency questionnaire and a energy-adjusted dietary phytochemical index (PI) was calculated. The odds ratios of breast cancer were assessed across energyadjusted PI quartile categories. The mean age of participants was 46.2±8.9 and 45.9±9.4 years in cases and controls, respectively. The mean PI across quartile categories was 13.9±2.6, 21.1±1.8, 26.7±2.1, 41.6±10.2 in the first, second, third and fourth quartiles, respectively. After adjustment for all potential confounders, the risk of breast cancer in the forth quartile of dietary PI was significantly decreased (OR=0.08, 95%CI=0.01-0.84). Higher intake of phytochemical-rich foods is associated with lower risk of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Dietary Phytochemical Index and the Risk of Breast Cancer: A Case Control Study in a Population of Iranian Women

Bahadoran

Karimi²,

Houshiarrad³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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“…In contrast, we detected strong associations between UGT2B15 genotype, diet, and APAP glucuronidation and sulfation. Two weeks of a controlled diet supplemented with citrus fruits, cruciferous vegetables, and soy foods, dietary sources of phytochemicals that increase UGT activity (Saracino and Lampe, 2007), had minor effects on salivary APAP pharmacokinetics but significantly increased urinary excretion of APAPG as a percentage of excreted metabolites, and decreased excretion of APAPS, particularly among carriers of the UGT2B15*1/*1 genotype.…”

Section: Discussionmentioning

confidence: 99%

“…The F&V diet included components of the basal diet supplemented with cruciferous vegetables (broccoli, cabbage, and daikon radish sprouts), soy foods (soy milk, veggies slices, tofu, and roasted soy nuts), and citrus fruits (grapefruit and orange juices, orange/grapefruit segments, and dried orange peel). We chose plant foods that were shown in previous animal and human studies to induce UGT genotypes (Saracino and Lampe, 2007). The amount of fruits and vegetables provided to the participants was at levels equivalent to approximately 10 servings daily; however, we dosed on the basis of participant's body weight (i.e., per 5 kg of body weight); details are provided elsewhere (Chang et al, 2007).…”

Section: Methodsmentioning

confidence: 99%

“…Bioactive food components in plants (e.g., phytochemicals such as isoflavones, flavonoids, coumarins, monoterpenes, allyl sulfides, isothiocyanates, and those found in green-tea extract) increase hepatic UGT activity in rodents (for review, see Saracino and Lampe, 2007), and several lines of evidence support an effect of diet on UGT activity in humans (Pantuck et al, 1984;Navarro et al, 2009). Thus, both dietary habits and genetic polymorphisms in UGTs may affect the toxicity of xenobiotics and the potency of drugs and steroid hormones by altering the amounts and activities of UGTs in the liver and other tissues.…”

Section: Introductionmentioning

confidence: 99%

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UGT1A6andUGT2B15Polymorphisms and Acetaminophen Conjugation in Response to a Randomized, Controlled Diet of Select Fruits and Vegetables

Navarro

Chen

et al. 2011

Drug Metab Dispos

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ABSTRACT:Acetaminophen (APAP) glucuronidation is thought to occur mainly by UDP-glucuronosyltransferases (UGT) in the UGT1A family. Interindividual variation in APAP glucuronidation is attributed in part to polymorphisms in UGT1As. However, evidence suggests that UGT2B15 may also be important. We evaluated, in a controlled feeding trial, whether APAP conjugation differed by UGT1A6 and UGT2B15 genotypes and whether supplementation of known dietary inducers of UGT (crucifers, soy, and citrus) modulated APAP glucuronidation compared with a diet devoid of fruits and vegetables (F&V). Healthy adults (n ‫؍‬ 66) received 1000 mg of APAP orally on days 7 and 14 of each 2-week feeding period and collected saliva and urine over 12 h. Urinary recovery of the percentage of the APAP dose as free APAP was higher (P ‫؍‬ 0.02), and the percentage as APAP glucuronide (APAPG) was lower (P ‫؍‬ 0.004) in women. The percentage of APAP was higher among UGT1A6*1/*1 genotypes, relative to *1/*2 and *2/*2 genotypes (P ‫؍‬ 0.045). For UGT2B15, the percentage of APAPG decreased (P < 0.0001) and that of APAP sulfate increased (P ‫؍‬ 0.002) in an allelic dosedependent manner across genotypes from *1/*1 to *2/*2. There was a significant diet ؋ UGT2B15 genotype interaction for the APAPG ratio (APAPG/total metabolites ؋ 100) (P ‫؍‬ 0.03), with *1/*1 genotypes having an approximately 2-fold higher F&V to basal diet difference in response compared with *1/*2 and *2/*2 genotypes. Salivary APAP maximum concentration (C max ) was significantly higher in women (P ‫؍‬ 0.0003), with F&V (P ‫؍‬ 0.003), and among UGT1A6*2/*2 and UGT2B15*1/*2 genotypes (P ‫؍‬ 0.02 and 0.002, respectively). APAP half-life was longer in UGT2B15*2/*2 genotypes with F&V (P ‫؍‬ 0.009). APAP glucuronidation was significantly influenced by the UGT2B15*2 polymorphism, supporting a role in vivo for UGT2B15 in APAP glucuronidation, whereas the contribution of UGT1A6*2 was modest. Selected F&V known to affect UGT activity led to greater glucuronidation and less sulfation.

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“…Commonly induced phase II enzymes include glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase (NQO-1), and UDP-glucuronosyltransferase (UGT). GSTs generally catalyze the nucleophilic addition of GSH to electrophilic groups of a broad spectrum of xenobiotics (26) while UGTs catalyze the transfer of glucuronic acid to hydrophobic chemicals, facilitating their detoxification and excretion (27). NQO-1 catalyzes the beneficial two-electron reduction of quinones to Fig.…”

Section: Induction Of Phase II Dmesmentioning

confidence: 99%

Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

Cheung

Kong

2009

AAPS J

325

289

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Abstract. Development of cancer is a long-term and multistep process which comprises initiation, progression, and promotion stages of carcinogenesis. Conceivably, it can be targeted and interrupted along these different stages. In this context, many naturally occurring dietary compounds from our daily consumption of fruits and vegetables have been shown to possess cancer preventive effects. Phenethyl isothiocyanate (PEITC) and sulforaphane (SFN) are two of the most widely investigated isothiocyanates from the crucifers. Both have been found to be very potent chemopreventive agents in numerous animal carcinogenesis models as well as cell culture models. They exert their chemopreventive effects through regulation of diverse molecular mechanisms. In this review, we will discuss the molecular targets of PEITC and SFN potentially involved in cancer chemoprevention. These include the regulation of drugmetabolizing enzymes phase I cytochrome P450s and phase II metabolizing enzymes. In addition, the signaling pathways including Nrf2-Keap 1, anti-inflammatory NFκB, apoptosis, and cell cycle arrest as well as some receptors will also be discussed. Furthermore, we will also discuss the similarities and their potential differences in the regulation of these molecular targets by PEITC and SFN.

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Phytochemical Regulation of UDP-Glucuronosyltransferases: Implications for Cancer Prevention

Cited by 41 publications

References 296 publications

Dietary Phytochemical Index and the Risk of Breast Cancer: A Case Control Study in a Population of Iranian Women

Dietary Phytochemical Index and the Risk of Breast Cancer: A Case Control Study in a Population of Iranian Women

UGT1A6andUGT2B15Polymorphisms and Acetaminophen Conjugation in Response to a Randomized, Controlled Diet of Select Fruits and Vegetables

Molecular Targets of Dietary Phenethyl Isothiocyanate and Sulforaphane for Cancer Chemoprevention

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