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ABSTRACT: OBJECTIVES: Small aromatic compounds like flavonoids can intercalate with DNA molecules bringing about conformational changes leading to reduced replication and transcription. Here, we have examined one dietary flavonoid, quercetin (found in many fruit and vegetables), for possible anti-cancer effects, on HeLa cells originally derived from a case of human cervical cancer.
MATERIAL AND METHODS: By circular dichroism spectroscopy we tested whether quercetin effectively interacted with DNA to bring about conformational changes that would strongly inhibit proliferation and migration of the HeLa cells. Cytotoxic effects of quercetin on cancer/normal cells, if any, were determined by MTT assay and such depolarization of mitochondrial membrane potential, as a consequence of quercetin treatment, and accumulation of reactive oxygen species (ROS) also were studied, by FACS analysis and expression profiles of different anti- and pro-apoptotic genes and their products were determined.
RESULTS: Quercetin intercalated with calf thymus cell DNA and HeLa cell DNA and inhibition of anti-apoptotic AKT and Bcl-2 expression were observed. Levels of mitochondrial cytochrome-c were elevated and depolarization of mitochondrial membrane potential occurred with increase of ROS; upregulation of expression of p53 and caspase-3 activity were also noted. These alterations in signalling proteins and externalization of phosphotidyl serine residues were involved with initiation of apoptosis. Reduced AKT expression suggested reduction in cell proliferation and metastasis potential, with arrest of the cell cycle at G2/M.
CONCLUSION: Quercetin would have potential for use in cervical cancer chemotherapy.
Cell Proliferation 04/2013; 46(2):153-163. · 2.52 Impact Factor
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ABSTRACT: Objective: To examine if potentized homeopathic drug Arsenicum Album 30C (Ars Alb 30C) can reduce sodium arsenite-induced toxicity in Escherichia coli.
METHODS:
E. coli were exposed to low arsenite insult after they grew up to log phase in standard Luria-Bertani medium. E. coli were treated with 1 or 2 mmol/L sodium arsenite alone (control), or Ars Alb 30C was added to the medium of a subset of sodium arsenite-treated bacteria (drug-treated), or homeopathically agitated alcohol was added to the medium containing a subset of sodium arsenite-treated bacteria (placebo-treated). A sub-set of untreated E. coli served as the negative control. Glucose uptake, specific activities of hexokinase, lipid peroxidase (LPO), superoxide dismutase (SOD) and catalase, intra- and extra-cellular sodium arsenite content, cell growth, cell membrane potential, DNA damage, intracellular reactive oxygen species (ROS), adenosine triphosphate (ATP) and free glutathione content and expressions of arsB and ptsG gene in normal control, sodium arsenite-treated, drug-treated and placebo-treated E. coli were analyzed. Treatments were blinded and randomized.
RESULTS:
In sodium arsenite-treated E. coli, glucose uptake, intracellular ROS, LPO and DNA damage increased along with decrease in the specific activities of hexokinase, SOD and catalase, intracellular ATP and free glutathione contents and cell membrane potential and growth, and there were increases in expression levels of arsB gene and ptsG gene. Ars Alb 30C administration reduced arsenic toxicity in E. coli by inhibiting generation of ROS and increasing tolerance to arsenite toxicity and cell growth.
CONCLUSION:
Ars Alb 30C ameliorated arsenic toxicity and DNA damage, validating efficacy of ultra-highly diluted remedies used in homeopathy.
Journal of Chinese Integrative Medicine 01/2012; 10(2-3):210-227.
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ABSTRACT: A highly selective and sensitive fluorescent Zn(2+) sensor, 2,6-bis(2-hydroxy-benzoic acid hydrazide)-4-methylphenol (1), was designed and synthesized. In aqueous THF (4 : 6 v/v) ligand 1 induces a 2 : 1 complex formation with respect to Zn(2+) at physiological pH. This probe features visible light excitation(390 nm) and emission (490 nm) profiles, excellent selectivity responses for Zn(2+)over other competing biological metal ions with K(d) < 1 pM(2), LOD < 1 ng L(-1) and about 680 fold enhancement in fluorescent intensity upon Zn(2+) binding. It also exhibits cell permeability and intracellular Zn(2+) sensing in A375 human melanoma cancer cell.
Organic & Biomolecular Chemistry 01/2012; · 3.70 Impact Factor
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ABSTRACT: Arsenic toxicity induces type 2 diabetes via stress mediated pathway. In this study, we attempt to reveal how sodium arsenite (iAs) could induce stress mediated impaired insulin signaling in mice and if an isolated active fraction of ginger, [6]-gingerol could attenuate the iAs intoxicated hyperglycemic condition of mice and bring about improvement in their impaired insulin signaling. [6]-Gingerol treatment reduced elevated blood glucose level and oxidative stress by enhancing activity of super oxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and GSH. [6]-Gingerol also helped in increasing plasma insulin level, brought down after iAs exposure. iAs treatment to primary cell culture of β-cells and hepatocytes in vitro produced cyto-degenerative effect and accumulated reactive oxygen species (ROS) in pancreatic β-cells and hepatocytes of mice. [6]-Gingerol appeared to inhibit/intervene iAs induced cyto-degeneration of pancreatic β-cells and hepatocytes, helped in scavenging the free radicals. The over-expression of TNFα and IL6 in iAs intoxicated mice was down-regulated by [6]-gingerol treatment. iAs intoxication reduced expression levels of GLUT4, IRS-1, IRS-2, PI3K, AKT, PPARγ signaling molecules; [6]-gingerol mediated its action through enhancing the expressions of these signaling molecules, both at protein and mRNA levels. Thus, our results suggest that [6]-gingerol possesses an anti-hyperglycemic property and can improve impaired insulin signaling in arsenic intoxicated mice.
Toxicology Letters 01/2012; 210(1-1):34-43. · 3.23 Impact Factor
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ABSTRACT: Mesoporous phosphosilicate nanoparticles of hollow sphere architecture have been prepared hydrothermally for the first time under acidic pH conditions and this material is found to be efficient in encapsulating an antibiotic drug and its controlled release at physiological pH for possible cargo delivery applications.
Chemical Communications 01/2012; 48(23-2):2891-3. · 6.17 Impact Factor