Plant polyphenols mobilize nuclear copper in human peripheral lymphocytes leading to oxidatively generated DNA breakage: Implications for an anticancer mechanism

Shamim, Uzma; Hanif, Sarmad; Ullah, Mohammad Fahad; Azmi, Asfar S.; Bhat, Ramesa Shafi; Hadi, S. M.

doi:10.1080/10715760802302251

Cited by 44 publications

(68 citation statements)

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“…2B). Use of permeabilized lymphocytes allows the direct interaction of isoflavones with cell nuclei at physiological pH, eliminating the need to first lyse the cells at alkaline pH and then re-suspending them at neutral pH as we have done previously [31]. Thus, considerably greater DNA breakage should be observed in permeabilized lymphocytes as compared with the intact cells.…”

Section: Dna Breakage By Isoflavones In Cellular and Permeabilized Lymentioning

confidence: 87%

“…The FOX assay [35] 31 ion to the ferric-sensitive dye xylenol orange, yielding an orange to purple complex, which is measured at 560 nm. The reaction mixture contained the isoflavones along with the incubation medium used in the treatment of lymphocytes.…”

Section: Detection Of H 2 O 2 In the Incubation Medium By Fox Assaymentioning

confidence: 99%

“…The reaction mixture contained the isoflavones along with the incubation medium used in the treatment of lymphocytes. After incubation for 2 h at 371C, an aliquot of 200 mL was analyzed for H 2 O 2 formation [31].…”

Section: Detection Of H 2 O 2 In the Incubation Medium By Fox Assaymentioning

confidence: 99%

“…The slides were allowed to gel at 41C for 10 min. The layered lymphocytes on slides were then subjected to treatment with isoflavones and processed further for Comet assay as already described [31].…”

Section: Viability Assessment Of Lymphocytesmentioning

confidence: 99%

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Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A

Ullah

Shamim

Hanif

et al. 2009

Molecular Nutrition Food Res

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Epidemiological studies have indicated that populations with high isoflavone intake through soy consumption have lower rates of breast, prostate, and colon cancer. The isoflavone polyphenol genistein in soybean is considered to be a potent chemopreventive agent against cancer. In order to explore the chemical basis of chemopreventive activity of genistein, in this paper we have examined the structure-activity relationship between genistein and its structural analogue biochanin A. We show that both genistein and its methylated derivative biochanin A are able to mobilize nuclear copper in human lymphocyte, leading to degradation of cellular DNA. However, the relative rate of DNA breakage was greater in the case of genistein. Further, the cellular DNA degradation was inhibited by copper chelator (neocuproine/bathocuproine) but not by compounds that specifically bind iron and zinc (desferrioxamine mesylate and histidine, respectively). We also compared the antioxidant activity of the two isoflavones against tert-butylhydroperoxide-induced oxidative breakage in lymphocytes. Again genistein was found to be more effective than biochanin A in providing protection against oxidative stress induced by tert-butylhydroperoxide. It would therefore appear that the structural features of isoflavones that are important for antioxidant properties are also the ones that contribute to their pro-oxidant action through a mechanism that involves redox cycling of chromatin-bound nuclear copper.

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Section: Dna Breakage By Isoflavones In Cellular and Permeabilized Lymentioning

confidence: 87%

Section: Detection Of H 2 O 2 In the Incubation Medium By Fox Assaymentioning

confidence: 99%

Section: Detection Of H 2 O 2 In the Incubation Medium By Fox Assaymentioning

confidence: 99%

Section: Viability Assessment Of Lymphocytesmentioning

confidence: 99%

See 2 more Smart Citations

Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A

Ullah

Shamim

Hanif

et al. 2009

Molecular Nutrition Food Res

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“…HCAs and their derivatives have a broad spectrum of biological activities including antitumoral [42][43][44][45], antimicrobial [46], antioxidant [47][48][49][50][51][52] and neuroprotective effects [53][54][55].…”

Section: Coo Hmentioning

confidence: 99%

Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships

Razzaghi‐Asl¹,

Garrido²,

Khazraei³

et al. 2013

CMC

167

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Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties. Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxi-dant activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the car-boxylic function that include esterification and amidation process. Furthermore, reports that have addressed the influence of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activ-ity were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimiza-tion of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be use-ful for management of oxidative stress-related diseases.Keywords: Antioxidant, hydroxycinnamic acids, in vitro, ROS, structure-activity relationships. OXIDATIVE STRESS AND ANTIOXIDANTSReactive oxygen species (ROS) are oxygen derived molecules that readily react with other compounds and macromolecules and oxidize them. Some representative exam-ples of these species include superoxide (O2•-), hydroxy (HO • ) and peroxy (ROO • ) radicals, hydrogen peroxide (H2O2) and singletROS are involved in important physiological processes such as immune response, gene expression, signal transduc-tion and growth regulation [5,6]; however if they are not kept under tight control by physiological antioxidant systems they will be able to oxidize and damage various biological molecules leading to a condition called oxidative stress [1,7,8]. In this regard, oxidative stress has been reported to be in-volved in the pathogenesis of diseases such as cancer [9], neurodegenerative diseases [10], stroke [11], and others [12,13].Since an important source of ROS comes from environment [14], with the industrial development and the change in life style, oxidative stress related diseases need a special attention [15].Antioxidants operate by preventing or slowing the progression of oxidative damage reactions [16,17]. An antioxidant has been defined as "any substance that delays, p...

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Chemical composition, antioxidant, antimicrobial and cytotoxic activities of Tagetes minuta and Ocimum basilicum essential oils

Shirazi

Gholami

Kavoosi

et al. 2014

Food Science & Nutrition

126

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Chemical composition, antioxidant, antimicrobial and cytotoxic activities of Tagetes minuta (TM) essential oil (TMO) and Ocimum basilicum (OB) essential oil (OBO) were examined. The main components for TMO were dihydrotagetone (33.9%), E-ocimene (19.9%), tagetone (16.1%), cis-β-ocimene (7.9%), Z-ocimene (5.3%), limonene (3.1%) and epoxyocimene (2.03%). The main components for OBO were methylchavicol (46.9%), geranial (19.1%), neral (15.15%), geraniol (3.0%), nerol (3.0%), caryophyllene (2.4%). Inhibitory concentrations (IC50) for reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavenging were 12–17 and 200–250 μg/mL of TMO and OBO, respectively. Minimal inhibitory concentration (MIC) against Salmonella typhi,Escherichia coli,Staphylococcus aureus,Bacillus subtilis,Aspergillus niger, and Candida albicans were 150 ± 8, 165 ± 9, 67 ± 8, 75 ± 7, 135 ± 15, and 115 ± 8 μg/mL of TMO, respectively. MIC for S. typhi,E. coli,S. aureus,B. subtilis,A. niger, and C. albicans were 145 ± 8, 160 ± 7, 45 ± 4, 40 ± 3, 80 ± 9, and 95 ± 7 μg/mL of OBO, respectively. IC50 for nasopharyngeal cancer cell line (KB) and liver hepatocellular carcinoma cell line (HepG2) were 75 ± 5 and 70 ± 4 μg/mL of TMO, respectively. IC50 for KB and HepG2 were 45 ± 4 and 40 ± 3 μg/mL of OBO, respectively. Thus, they could be used as an effective source of natural antioxidant and antibacterial additive to protect foods from oxidative damages and foodborne pathogens. Furthermore, they could be promising candidate for antitumor drug design.

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Plant polyphenols mobilize nuclear copper in human peripheral lymphocytes leading to oxidatively generated DNA breakage: Implications for an anticancer mechanism

Cited by 44 publications

References 50 publications

Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A

Cellular DNA breakage by soy isoflavone genistein and its methylated structural analogue biochanin A

Antioxidant Properties of Hydroxycinnamic Acids: A Review of Structure- Activity Relationships

Chemical composition, antioxidant, antimicrobial and cytotoxic activities of Tagetes minuta and Ocimum basilicum essential oils

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