Study on the Interactions of Kaempferol and Quercetin with Intravenous Immunoglobulin by Fluorescence Quenching, Fourier Transformation Infrared Spectroscopy and Circular Dichroism Spectroscopy

Abstract

Initially used as replacement therapy for patients with primary and secondary immune deficiencies, intravenous immunoglobulin (IVIG), the human serum immunoglobulin (Ig) fraction that is mainly composed of normal human polyclonal IgG obtained from plasma pools from a large number of healthy blood donors, is now widely used for the treatment of a large number of autoimmune and systemic inflammatory diseases. 1,2) Recently, great attention has been paid to IVIG potential use as adjuvant anti-neoplastic agent.3-5) Studies on the anticancer alkaloid vindesine (VDS) conjugates of the anti-CEA (carcinoembryonic antigen) antibodies against a colorectal tumor xenograft revealed that antibody 14.95.55 (IgG2a) suppressed tumor growth both alone and as a VDS conjugate, while 11.285.14 (IgG1) produced only a slight effect alone but an almost complete and lasting suppression of tumor growth as a VDS conjugate. Acute studies showed that VDS-11.285.14 conjugate was considerably less toxic than free VDS in Balb/c mice.6) It has been revealed that there are different transfer mechanism between the drug-protein conjugates and free drugs transferred into cells, and the conjugates can reduce the toxicity of drugs, resulting in a prolongation of survival time.7) Studies on the efficacy of an IgG F(ab) 2 preparation against taxol-induced C activation revealed that at a therapeutically relevant dose level (10 mg/ml), this Fc-depleted IgG caused significant suppression of taxol-induced SC5b-9 formation, but replacing IVIG with 10 mg/ml human serum albumin (HSA) caused no inhibition of taxolinduced rise of SC5b-9. 8) Also, it is reported that within a range of molar concentration ratio of taxol to IVIG, the interaction of IVIG with taxol can inhibit taxol from crystallizing in aqueous solution.9) Studies in vitro have revealed that IVIG may stimulate the production of IL-12, an anti-tumor and anti-angiogenic cytokine, and enhanced NK cell activity.4) Studies also revealed that IVIG can decrease the level of matrix metalloproteinase-9 (MMP-9) expression in the U937 monocyte line with a decrease in the m-RNA level of MMP-9 that participates in basement membrane degradation, a vital step in the invasion of metastatic cancer cells. So, IVIG may serve as an adjuvant therapy in cancer due to its anti-neoplastic properties that may synergize with more specific MMP inhibitors and other anti-cancer drugs. 10,11) In addition, IgG presents itself in the blood of adults at 9.5-12.5 mg/ml, and as one of human plasma proteins, it is capable of binding an extraordinarily diverse range of metabolites, drugs, organic compounds and relevant antigens. [12][13][14] With the remarkable binding properties, IVIG can serve as an important transport protein for drugs, which may have important roles in the discovery of novel drug delivery system and targeted drug therapy. By using its high-safety profile, clinicians may construct new protocols for patients.Flavonols are plant pigments that are ubiquitous in nature. Kaempferol (3,4Ј,5,7-pentahydroxyflavone), quer...

Mono-Ubiquitination of Nuclear Annexin A1 and Mutagenesis

“…However, recent studies have shown that the downregulation of annexins in certain types of malignant cancers is mainly attributable to epigenetic regulation by DNA methylation and histone acetylation, and to deletion of the annexin genes due to chromosomal instability following malignant transformation (Lim & Pervaiz, 2007). In esophageal epithelial carcinoma cells, nuclear annexin A1 is increased by its translocation from the cytosol, and cytosolic annexin A1 is consequently decreased (Liu et al, 2008). Therefore, it is proposed that nuclear annexin A1 rather than cytosolic annexin A1 is more closely associated with cell transformation, namely, cancer initiation¸ while changes of annexin A1 expression may not be involved in tumorigenesis.…”

Carboxylate-Dependent Gelation of a Monoclonal Antibody

“…The smaller bundles were made up of straight single filaments with an average diameter of 4 nm in agreement with the hydrodynamic size of unassembled MAb monomers measured by dynamic light scattering (not shown). FTIR and Raman spectroscopy, which are sensitive to the secondary structure of proteins (35,36), suggested that the assembly of MAb does not feature a significant change in secondary structure before and after the addition of citrate (not shown).…”

Crystal structures, antioxidation and DNA binding properties of Eu(III) complexes with Schiff-base ligands derived from 8-hydroxyquinoline-2-carboxyaldehyde and three aroylhydrazines

“…2 and the quenching data collected from the good linear relationship with P < 0.05 are listed in Table 3 [23]. All of the current values of K q are much greater than that of K q(max) (2.0 Â 10 10 M À1 s À1 ), the maximum quenching rate constant of bimolecular diffusion collision, which are indicative of static types of quenching mechanisms arisen from the formations of dark complexes between the fluorophores and quenching agents [50,51]. The EtBr-DNA quenching results also indicate that most of the EtBr molecules have been displaced from EtBr-DNA complex by every quencher at the approximate titration end point and that the intercalation takes place between the compound with DNA [26].…”

“…In the present study, the chelation between phenolic hydroxyl group and carbonyl group of 2-hydroxybenzoylhydrazine side chain of ligand 1b with free Fe 2+ (as catalyst [30]) in iron-EDTA reaction system may make the concentration of free Fe 2+ much lower so that the catalysis becomes very poor and the OH Å formation has been suppressed, thus the inhibitive effect of 1b detected for OH Å is higher than those of other ligands. On the other hand, the values of IC 50 with a notably different order of 2c < 2a < 2b. These results suggest that there are different mechanisms between scavenging or inhibiting OH Å and O ÀÅ 2 , which should be further studied in the future work.…”