β-Carotene Regulates NF-κB DNA-Binding Activity by a Redox Mechanism in Human Leukemia and Colon Adenocarcinoma Cells

Palozza, Paola; Serini, Simona; Torsello, Angela; Nicuolo, Fiorella Di; Piccioni, Elisabetta; Ubaldi, Vanessa; Pioli, Claudio; Wolf, Federica I.; Calviello, Gabriella

doi:10.1093/jn/133.2.381

Cited by 127 publications

(63 citation statements)

References 45 publications

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“…53 The same group of investigators reported earlier that ␤-carotene at doses responsible for growth-inhibitory effects in HT-29 cells, was able to regulate the redox regulation of NF-B and the subsequent expression of proteins, such as c-myc, involved in the induction of apoptosis. 54 However, it was discussed that the concentrations responsible for the prooxidant and the growth-inhibitory effects of ␤-carotene in this in vitro study would be reached in vivo in the serum of humans only with supplements containing very high doses of the carotenoids. 54 These in vitro studies clearly demonstrated that ␤-carotene and possibly other carotenoids inhibit colon cancer cells by their capability to induce apoptosis.…”

Section: Discussionmentioning

confidence: 90%

“…54 However, it was discussed that the concentrations responsible for the prooxidant and the growth-inhibitory effects of ␤-carotene in this in vitro study would be reached in vivo in the serum of humans only with supplements containing very high doses of the carotenoids. 54 These in vitro studies clearly demonstrated that ␤-carotene and possibly other carotenoids inhibit colon cancer cells by their capability to induce apoptosis.…”

Section: Discussionmentioning

confidence: 90%

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Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence

Raju

Swamy

Cooma

et al. 2004

Intl Journal of Cancer

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Epidemiological studies suggest that carotenoids such as ␤-carotene and lutein play an important role in reducing the risk for several cancers. However, in colon cancer there is ambiguity with regard to the role of these compounds in that both preventive effects and tumor promotion have been observed. In the present study we observed that male F344 rats were able to tolerate up to 2,500 ppm of ␤-carotene as well as of lutein. We have then assessed the chemopreventive efficacy of ␤-carotene and lutein at dose levels of ϳ4 and 8% of the 2,500 ppm tolerated dose (TD) and also ϳ40 and 80% of the TD on azoxymethane (AOM)-induced colon carcinogenesis, using aberrant crypt foci (ACF) as a surrogate biomarker for colon cancer. Throughout the experiments, 5-weekold male F344 rats were fed the control diet (modified AIN-76A) or experimental diets containing 100 or 200 ppm (ϳ4 or 8% of the 2,500 ppm TD), or 1,000 or 2,000 ppm (ϳ40 or 80% of the 2,500 ppm TD) of ␤-carotene and lutein (n‫01؍‬ rats/group). After 2 weeks on the experimental or control diets, all animals were injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). At 14 weeks of age, all rats were killed, and their colons were evaluated for ACF. Administration of 100 or 200 ppm of ␤-carotene inhibited AOM-induced total colonic ACF formation by 24% (p<0.01) and 36% (p<0.001), respectively, whereas lutein at 200 ppm produced a 27% inhibition (p<0.01) yet had no significant effect at the 100 ppm dose level. Surprisingly, administration of 1,000 or 2,000 ppm of ␤-carotene and lutein increased colonic ACF formation in a dose-dependent manner, i.e., to 124% and 144% for the former and 110% and 159% for the latter. These results clearly suggest that further studies are warranted to determine whether the increase in ACF incidence by high doses of ␤-carotene and lutein will also lead to an increase in tumor outcome. Taken together these data indicate that the chemopreventive activity of ␤-carotene and lutein against colon carcinogenesis depends on the dose level. © 2004 Wiley-Liss, Inc. Key words: colon cancer; aberrant crypt foci; chemoprevention; ␤-carotene; lutein Colorectal cancer is one of the leading causes of cancer deaths in both men and women in Western countries, including the United States. 1 Evidence from epidemiological studies and laboratory animal assays suggests a relationship between colon cancer risk and several dietary factors. 2,3 Identification of naturally occurring carcinogens and anti-carcinogens should lead not only to an understanding of carcinogenesis but should also provide strategies for cancer prevention. Several epidemiological studies have consistently demonstrated that people who have a high intake of vegetables and fruits that are rich in carotenoids had low risk of cancer. 4 -7 Possible cancer preventive effects of carotenoids have been established in several epidemiological and clinical studies by comparing serum levels of carotenoids in normal and cancer patients. 8 -10 Some studies also pointed to a possible relationshi...

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 90%

Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence

Raju

Swamy

Cooma

et al. 2004

Intl Journal of Cancer

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“…Blocking the NF-ĸB pathway stops cell proliferation, induces apoptosis and makes the cancer cell more susceptible to antitumor agents. Preliminary studies have demonstrated that β-carotene as well has the ability to modulate NF-ĸB signaling pathway by means of a redox mechanism to tumor cells (Palozza et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

Cytotoxic Potential of Antioxidants from Tomatoes on Tumoral Cells

Cenariu¹,

Pintea²,

Fischer‐Fodor³

et al. 2015

BUASVMCN-VM

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Tomatoes (Lycopersicon esculentum Mill.) are known to contain various antioxidants such as lycopene and other carotenoids, which were proven to have antineoplastic activity. The aim of the present study was to obtain and characterize a whole tomato extract in order to show the amount and type of antioxidants contained, as well as to assess the cytotoxic potential of such extracts on the HepG2 tumoral cell line. Tomato extracts were obtained using the light petroleum/ethyl acetate/methanol method and characterized by HPLC. HepG2 liver hepatocellular carcinoma cell line was grown in Eagle's Minimum Essential Medium (EMEM) supplemented with 10% FBS. As soon as subconfluency was reached cells were transferred into 96 well plates and treated with serial dilutions of the tomato extract. Cytotoxicity of the extracts was assessed using the MTT dye, in comparison with untreated cells and IC50 was established. The extraction method proved to be a very efficient one, yielding significant amounts of carotenoid pigments, including lycopene, β-carotene, γ-carotene and others, as shown by the HPLC analysis. The antioxidants contained by the extracts showed significant cytotoxicity on HepG2 liver hepatocellular carcinoma cell line, being able to visibly inhibit cellular development in vitro. The present study showed the cytotoxic influence that antioxidants extracted from tomatoes exert on the in vitro development of a hepatocellular carcinoma cell line, opening new perspectives for in vivo studies, involving patients with hepatic cancer.

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“…31,32) The anti-oxidative/anti-inflammatory effects of thiol molecules (glutathione and N-acetyl-L-cysteine), and dietary polyphenols (quercetin and resveratol) have all been shown to play a role in controlling NF-kB activation with subsequent effects on inflammatory gene expression. 33,34) Our recent study reported that betaine suppressed the redox-sensitive transcription factor, NF-kB, in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Betaine Modulates Age-Related NF-.KAPPA.B by Thiol-Enhancing Action

Go¹,

Jung²,

Kim³

et al. 2007

Biological & Pharmaceutical Bulletin

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Oxidative stress is a condition where the reduction and oxidation (redox) balance between reactive species (RS) such as superoxide anion ( · O 2 Ϫ ), hydrogen peroxide (H 2 O 2 ), peroxynitrite (ONOO Ϫ ), and hydroxyl radical ( · OH) and antioxidant species such as glutathione (GSH) and thioredoxin (Trx) is disrupted. 1-3)Oxidant-related reactions and cellular redox imbalance are implicated in a number of human diseases and aging. 4,5) Further, biological systems are protected against oxidative stress by a diversity of mechanisms designed to suppress the pernicious oxidative pathway. Numerous antioxidants are known to forestall oxidative damage or to limit its propagation. GSH, is a most abundant and an important intracellular thiol redox regulator that plays a major role in both the maintenance of redox status and in the protection of cells from electrophilic and oxidative attacks. 6) Many researchers who are interested in studying changes in the redox status rely on GSH levels as a reliable indicator of an organism's redox status. GSH depletion causes various biochemical and pathological changes, including mitochondrial dysfunction and swelling. 7,8) GSH depletion also is linked to aging processes, cardiovascular and neurodegenerative diseases. [9][10][11] A gradual rise of oxidative stress due to disrupted redox regulation during aging can influence the gene transcription and signal transduction pathways. The gene response to oxidative stress is seen due to the redox-sensitive transcription factors that modulate gene regulation. NF-kB is among the most important transcription factors shown to be exquisitely sensitive to oxidative stress conditions. 12) NF-kB regulates the activity of many genes, such as cyclooxygenase-2 (COX-2), TNFa, inducible NO synthase, and adhesion molecules. 13,14) Most of genes activated by NF-kB transcription factor are shown to be pro-inflammatory and involved in inflammation processes. In aged organisms, inflammatory reactions lead to a chronic pro-inflammatory state as evidenced from the activation of pro-inflammatory gene expression. 15,16) Betaine was first discovered in the juice of sugar beets (Beta vulgaris) in the 19th century and now found widely in various microorganisms, plant, and animals. 17) In Southeast Asia, this water-soluble component of Lycium chinensis has been used in traditional oriental medicine for the treatment of hepatic disorders.18) The biological function of betaine is proposed to act as an osmolyte to protect cells under stress 19) as a catabolic source of methyl through transmethylation in many biochemical pathways.17) As a methyl donor, betaine participates in methionine metabolism by its ability to convert homocysteine (Hcy) to methionine. 17,20) Recently, our lab published a paper on betaine's ability to suppress NF-kB during aging.15) However, this paper did not fully address how betaine exerts its regulatory role in the suppression of NF-kB.In the present study, we attempt to document that betaine decreases NF-kB through modulation of the cellular ...

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β-Carotene Regulates NF-κB DNA-Binding Activity by a Redox Mechanism in Human Leukemia and Colon Adenocarcinoma Cells

Cited by 127 publications

References 45 publications

Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence

Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence

Cytotoxic Potential of Antioxidants from Tomatoes on Tumoral Cells

Betaine Modulates Age-Related NF-.KAPPA.B by Thiol-Enhancing Action

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