Studies on the anticlastogenic effect of turmeric and curcumin on cyclophosphamide and mitomycin C in vivo.
TL;DR: Although curcumin is reported to be the active chemopreventive principle in turmeric effective against a number of potential carcinogens in several experimental systems, it was virtually ineffective against the clastogenicity of CP or MMC at the doses tested.
About: This article is published in Food and Chemical Toxicology.The article was published on 1998-01-01. It has received 32 citations till now. The article focuses on the topics: Curcumin & Chromosome aberration.
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TL;DR: It is suggested that formaldehyde induced genotoxicity through its ROS and lipid peroxidase activity and caused DPCs effects in A549 cells.
Abstract: Formaldehyde is ubiquitous in the environment. It is known to be a genotoxic substance. We hypothesized that reactive oxygen species (ROS) and lipid peroxidation are involved in formaldehyde-induced genotoxicity in human lung cancer cell lines A549. To test this hypothesis, we investigated the effects of antioxidant on formaldehyde-induced genotoxicity in A549 Cell Lines. Formaldehyde exposure caused induction of DNA-protein cross-links (DPCs). Curcumin is an important antioxidant. Formaldehyde significantly increased malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity. In addition, the activation of NF-κB and AP-1 were induced by formaldehyde treatment. Pretreatment with curcumin counteracted formaldehyde-induced oxidative stress, ameliorated DPCs and attenuated activation of NF-κB and AP-1 in A549 Cell Lines. These results, taken together, suggest that formaldehyde induced genotoxicity through its ROS and lipid peroxidase activity and caused DPCs effects in A549 cells.
29 citations
Cites background from "Studies on the anticlastogenic effe..."
...However, curcumin was weakly clastogenic in bone marrow cells of acutely treated mice (Mukhopadhyay et al., 1998)....
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TL;DR: The present commentary is a call to proceed slowly and with extreme caution in administering an oncofetal protein to human adult patients, a protein whose precise function and physiological roles are not yet fully understood.
Abstract: Dear Editor, In the course of the last decade, the possibility of employing full-length human alpha-fetoprotein (AFP) (FL-AFP) as a therapeutic agent for autoimmune diseases in clinical patients has become a reality in ongoing clinical trials. This is due, in part, to advances in both recombinant protein technology and improved methodologies in the isolation and large scale purification of naturally-occurring proteins. Although it is now possible to produce FL-AFP in scaled-up quantities, does this justify its use as a therapeutic agent (protein) in adult diseases and disorders? Are there safety issues involved with its use in patients, of what do they consist, and what are the possible risks, if any? The present commentary is a call to proceed slowly and with extreme caution in administering an oncofetal protein to human adult patients, a protein whose precise function and physiological roles are not yet fully understood. Even though the literature is replete with the biological activities ascribed to the FL-AFP, little is known regarding the administration of pharmacologic doses to human adults that normally display scant (5–8 ng/ml) levels in their bloodstream. Unless a patient has liver/germ cell cancer, hepatitis, cirrhosis, or a genetic disorder (i.e., ataxia telangiectasia), low AFP concentrations remain relatively constant throughout life. In contrast, the AFP levels in embryonic and fetal life can range from 20 ug/ml in amniotic fluids to 5 mg/ml in fetal serum. These concentrations, however, occur in cells and tissues undergoing frequent cell proliferation, adhesion, migration, differentiation and growth in the constantly changing milieu of the embryonic/fetal organism. Thus, FL-AFP exists and flourishes in fluctuating fetal environments requiring both molecular flexibility and adaptability. This is in dire contrast to albumin which interacts mostly with fully-differentiated cells and tissues of the adult organism. The potential risks involved with administering FL-AFP to clinical patients have, as root concerns, AFP’s ability to transition into multiple conformational variant states depending on its environmental surroundings such as pH, temperature, osmolality, excess ligand concentrations, oxidation and heat/ glucose shock. The silent danger of treating adult human patients with therapeutic doses of FL-AFP lies in its reversible and transient denaturation (conformational) states which bestow on AFP a rigid-to-flexible vacillation that exits between a compactly-folded form and an extended or open form. HAFP has a remarkably hydrophilicexposed molecular surface at neutral pH and possesses extensive hydrophobic binding sites located in concealed molecular crevices. The immunochemistry of the FL-AFP molecule has further revealed clusters of five major antigenic epitopes and one major occult epitope which gives rise to open and cryptic forms of AFP depending on its natured versus denatured state, respectively. Finally, FL-AFP has also been demonstrated to dimerize with other proteins, such as nuclear receptors (i.e., retinoic receptor), transcription factors and caspases all of which can result in promoting growth of tumor cells. FL-AFP has been reported to transition through a molten globule form dependent on extremes of pH, a situation commonly found in the cytoplasm of cells following protein uptake. The FL-AFP molecule is known to undergo a slight denaturation and unfolding through a molten globule state, which encompasses a loosening of the tertiary packing while leaving the secondary structure of the molecule intact. In contrast, the unfolding–refolding transition states are less common with human albumin, due to its more rigid compact structure resulting from a higher number of disulfide bridges in the molecule. AFP’s tertiary form is known to be under ligand binding control; thus, ligand concentration can affect its biological activities. Moreover, a relationship exists between the conformational state and the biological activity of AFP as exemplified in a report that tumor and fetal forms of AFP were found to differ in their conformationally-dependent expressions of epitope variants. Such transitional variants could conceivably be formed following the injection of FL-AFP into clinical patients and could result in unwanted targeting and aberrant signal transduction of AFP leading to conditions of inappropriate and untimely cell growth inhibition and/or enhancement. A further potential risk in the therapeutic use of FL-AFP, especially after multiple treatments, is the long-term effects on the growth, development and progression of small tumor foci which may not always be observable during human clinical trials. An effect that might result from extended administration of pharmacologic doses of FL-AFP is the initiation of tumor formation as previously described. This induction could result from the transformation of pretumor to tumor cells which have evaded immune surveillance in cancer-susceptible individuals, such as in hepatitis or cirrhotic patents; such groups are at risk for developing hepatomas (see later). FL-AFP has also been reported to promote or up-regulate tumor cell proliferation, cell cycle progression, angiogenesis Le tt er s to th e E di to r
23 citations
Cites background from "Studies on the anticlastogenic effe..."
...ligand binding control; thus, ligand concentration can affect its biological activities.(10,11) Moreover, a relationship exists...
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TL;DR: It is concluded from the present study that turmeric and ginger can be helpful in the therapy of chronic arsenic toxicity in calves and give protection from possible damage caused by arsenic exposure.
15 citations
TL;DR: Os efeitos de curcuma e curcumina na frequencia de aberracoes cromossomicas induzidas pelo agente radiomimetico bleomicina foram investigados em celulas do ovario de hamster chines.
Abstract: Antioxidantes de ocorrencia natural tem sido exaustivamente estudados quanto a sua capacidade de proteger organimos e celulas contra danos oxidativos. Muitos constituintes das plantas, incluindo curcuma e curcumina, parecem ser potentes antimutagenos e antioxidantes. Os efeitos de curcuma e curcumina na frequencia de aberracoes cromossomicas induzidas pelo agente radiomimetico bleomicina (BLM) foram investigados em celulas do ovario de hamster chines (CHO). Tres concentracoes de cada droga, curcuma (100, 250 e 500 mg/ml) e curcumina (2,5, 5,0 e 10 mg/ml), foram combinadas com BLM (10 mg/ml) em celulas CHO tratadas durante as fases G1/S, S ou G2/S do ciclo celular. Nem curcuma nem curcumina evitaram o dano cromossomico induzido pela BLM em fase alguma do ciclo celular. Ao contrario, a potenciacao da clastogenicidade da BLM pelo curcumina foi nitidamente observada em celulas tratadas durante as fases S e G2/S. A curcumina tambem se mostrou clastogenica na dose de 10 mg/ml nos protocolos de tratamento de 9 e 13 h. Contudo, o mecanismo exato pelo qual a curcumina produziu efeitos potenciadores e clastogenicos permanece desconhecido.
15 citations
Cites background from "Studies on the anticlastogenic effe..."
...However, curcumin and turmeric could not inhibit cyclophosphamide- or mitomycin-C-induced chromosomal aberrations in mice (Mukhopadhyay et al., 1998)....
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...Mukhopadhyay et al. (1998) reported a slight increase in the number of chromosomal aberrations in acutely treated mice by curcumin....
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...However, it induced chromosomal damage in plant systems (Abraham et al., 1976) and was weakly clastogenic in acutely treated mice (Mukhopadhyay et al., 1998)....
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References
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Book•
09 Jan 2018
TL;DR: Indian medicinal plants/, Indian medicinal plants /, مرکز فناوری اطلاعات و اصاع رسانی, کδاوρزی
Abstract: Indian medicinal plants / , Indian medicinal plants / , مرکز فناوری اطلاعات و اطلاع رسانی کشاورزی
8,252 citations
831 citations
Journal Article•
TL;DR: Investigation of the chemopreventive action of dietary curcumin on azoxymethane-induced colon carcinogenesis and also the modulating effect of this agent on the colonic mucosal and tumor phospholipase A2, phospholIPase C gamma 1, lipoxygenase, and cyclo oxygengenase activities in male F344 rats indicates that dietary administration ofCurcumin significantly inhibited incidence of colon adenocarcinomas.
Abstract: Human epidemiological and laboratory animal model studies have suggested that nonsteroidal antiinflammatory drugs reduce the risk of development of colon cancer and that the inhibition of colon carcinogenesis is mediated through the alteration in cyclooxygenase metabolism of arachidonic acid. Curcumin, which is a naturally occurring compound, is present in turmeric, possesses both antiinflammatory and antioxidant properties, and has been tested for its chemopreventive properties in skin and forestomach carcinogenesis. The present study was designed to investigate the chemopreventive action of dietary curcumin on azozymethaneinduced colon carcinogenesis and also the modulating effect of this agent on the colonic mucosal and tumor phospholipase A 2 , phospholipase Cγ1, lipoxygenase, and cyclooxygenase activities in male F344 rats. At 5 weeks of age, groups of animals were fed the control (modified AIN-76A) diet or a diet containing 2000 ppm of curcumin. At 7 weeks of age, all animals, except those in the vehicle (normal saline)-treated groups, were given two weekly s.c. injections of azoxymethane at a dose rate of 15 mg/kg body weight. All groups were continued on their respective dietary regimen until the termination of the experiment at 52 weeks after the carcinogen treatment. Colonic tumors were evaluated histopathologically. Colonic mucosa and tumors were analyzed for phospholipase A 2 , phospholipase Cγ1, ex vivo prostaglandin (PG) E 2 , cyclooxygenase, and lipoxygenase activities. The results indicate that dietary administration of curcumin significantly inhibited incidence of colon adenocarcinomas ( P P P P 57% compared to the control diet. Animals fed the curcumin diet showed decreased activities of colonic mucosal and tumor phospholipase A 2 (50%) and phospholipase Cγ1 (40%) and levels of PGE 2 (>38%). The formation of prostaglandins such as PGE 2 , PGF 2α , PGD 2 , 6-keto PGF 1α , and thromboxane B 2 through the cyclooxygenase system and production of 5( S )-, 8( S )-, 12( S )-, and 15( S )-hydroxyeicosatetraenoic acids via the lipoxygenase pathway from arachidonic acid were reduced in colonic mucosa and tumors of animals fed the curcumin diet as compared to control diet. Although the precise mechanism by which curcumin inhibits colon tumorigenesis remains to be elucidated, it is likely that the chemopreventive action, at least in part, may be related to the modulation of arachidonic acid metabolism.
706 citations
TL;DR: Salmonella/microsome tests (Ames tests) and chromosomal aberration tests in vitro using a Chinese hamster fibroblast cell line were carried out on 190 synthetic food additives and 52 food additives derived from natural sources, all of which are currently used in Japan.
634 citations