Antibacterial activity of Cuscuta reflexa stem and Corchorus olitorius seed.
The methanol extracts of Cuscuta reflexa stem and Corchorus olitorius seed showed a broad spectrum of antibacterial activity.
Anti-Bacterial Agents↗
Biomedical subjects
M Mandal
Publications and source records attributed to M Mandal.
The Akt inhibitor KP372-1 suppresses Akt activity and cell proliferation and induces apoptosis in thyroid cancer cells.
The phosphatidylinositol 3' kinase (PI3K)/phosphatase and tensin homologue deleted on chromosome ten/Akt pathway, which is a critical regulator of cell proliferation and survival, is mutated or activated in a wide variety of cancers. Akt appears to be a key central node in this pathway and thus is an attractive target for targeted molecular therapy. We demonstrated that Akt is highly phosphorylated in thyroid cancer cell lines and human thyroid cancer specimens, and hypothesised that KP372-1, an Akt inhibitor, would block signalling through the PI3K pathway and inhibit cell proliferation while inducing apoptosis of thyroid cancer cells. KP372-1 blocked signalling downstream of Akt in thyroid tumour cells, leading to inhibition of cell proliferation and increased apoptosis. As thyroid cancer consistently expresses phosphorylated Akt and KP372-1 effectively blocks Akt signalling, further preclinical evaluation of this compound for treatment of thyroid cancer is warranted.
Apoptosis↗
Removal of arsenic from water using hardened paste of Portland cement.
Portland cement has been used as a new low-cost adsorbent for the removal of arsenic from the water environment. In the batch experiments conducted at an initial concentration of 0.2 mg l(-1) of arsenate, it was found that up to 95% of arsenate could be removed. Kinetic profiles were developed for various conditions. The effect of adsorbent dose, effects of common ions such as Ca2+, Mg2+, Fe3+/Fe2+, Cl-, SO4(2-), NO3(-), PO4(3-) and the effect of pH was studied. Adsorption isotherm studies were performed and it was observed that the Freundlich isotherm was followed with a better correlation than the Langmuir isotherm. Arsenite could also be removed up to approximately 88% using the same material. A new detection method for arsenate/arsenite was developed for routine analysis of arsenic and used during the entire study.
Adsorption↗
Antibacterial activities and conformations of bovine beta-defensin BNBD-12 and analogs:structural and disulfide bridge requirements for activity.
Structure and biological activities of synthetic peptides corresponding to bovine neutrophil beta-defensin BNBD-12, GPLSC(1)GRNGGVC(2)IPIRC(3) PVPMRQIGTC(4) FGRPVKC(5) C(6)RSW with disulfide connectivities C(1)-C(5), C(2)-C(4) and C(3)-C(6) and its variants with one, two and three disulfide bridges have been investigated. Selective protection of cysteine thiols was necessary in the four and six cysteine containing peptides for the formation of disulfide connectivities as observed in BNBD-12. Circular dichroism (CD) spectra indicate that in aqueous medium, only a small fraction of molecules populate turn-like conformations. In the presence of micelles and lipid vesicles, the single, two and three disulfide containing peptides adopt beta-hairpin or beta-sheet structures. Antibacterial activity was observed for all the peptides, irrespective of the number of disulfide bridges or how they were connected. Our results suggest that a rigid beta-sheet structure or the presence of three disulfide bridges does not appear to be stringent requirements for antibacterial activity in beta-defensins.
Amino Acid Sequence↗
Antibacterial activities and conformations of synthetic alpha-defensin HNP-1 and analogs with one, two and three disulfide bridges.
Structure and biological activities of synthetic peptides corresponding to human alpha-defensin HNP-1, AC1YC2RIPAC3IAGERRYGTC4IYQGRLWAFC5C6 with the S-S connectivities: C1-C6, C2-C4, C3-C5, and its variants with one, two and three disulfide bridges were investigated. Oxidation of synthetic, reduced HNP-1 yielded a peptide with S-S connectivities C1-C3, C2-C4 and C5-C6, and not with the S-S linkages as in naturally occurring HNP-1. Selective protection of cysteine sulfhydryls was necessary for the formation of S-S bridges as in native HNP-1. Likewise, oxidation of peptide encompassing the segment from C2 to C5, resulted in the S-S linkages C2-C3 and C4-C5 instead of the expected linkage C2-C4 and C3-C5. Antibacterial activities were observed for all peptides, irrespective of how the S-S bridges were linked. Linear peptides without S-S bridges were inactive. Circular dichroism (CD) spectra suggest that peptides constrained by one and two S-S bridges do not form rigid beta-sheet structures in an aqueous environment. The spectrum of HNP-1 in an aqueous environment suggests the presence of a beta-hairpin conformation. In the presence of lipid vesicles, the S-S constrained peptides tend to adopt a beta-structure. Although the S-S connectivities observed in HNP-1 may be necessary for other physiological activities, such as chemotaxis, they are clearly not essential for antibacterial activity.
Amino Acid Sequence↗
Sex-specific finger-length patterns linked to behavioral variables: consistency across various human populations.
In humans, as in nonhuman primates, the digits of the hands are similar in length during early fetal development. Subsequently, differentiation leads to a patter of unequal finger lengths, described by George as the finger-length pattern. Recent work by Manning and colleagues suggested that digit length patterns are due to early influences of sex hormones. Most importantly for psychology, such patterns might also relate to cognitive activities that are influenced by early organizing actions of sex hormones. The exciting possibility of having an easily measurable indicator of early action of sex hormones that relates to behavior led us to examine the universality of digit length patterns. With samples from Brazil, Canada, India, Turkey, and Korea, we showed that patterns of distal extent of finger tips are similar across different human populations. Consistent sex differences were found across the samples, showing that the index finger in males extends less far distally relative to the middle finger than is the case for females and that the difference in distal extent between index and ring fingers, relative to the middle finger, is smaller in females than in males.
Adult↗
R-factor in Proteus vulgaris from ulcerative disease of fish, Channa punctatus.
A Proteus vulgaris isolated from external ulcers of the fresh water fish Channa punctatus showed multidrug resistance and heavy metal tolerance. The isolate from the ulcer showed resistance to chloramphenicol (Ch), nalidixic acid (Nx), streptomycin (Str) and tetracycline (Tet) with minimum inhibitory concentration (MIC) values of 750, 150, 75 and 125 microg/ml, respectively. The isolate showed growth in medium containing cadmium (Cd2+), up to a concentration of 2.5 mM indicating its heavy metal tolerance. Resistance to Ch, Str, Tet and Cd2+ of the isolate was lost after plasmid curing. Presence of plasmid DNA in the wild type and its absence in the cured P. vulgaris suggested that the resistance were plasmid mediated.
Animals↗
Growth factor regulation of the molecular chaperone calnexin.
Heregulin-beta1 (HRG) is a regulatory polypeptide having several distinct biological effects in mammary epithelial cells. To address the hypothesis that HRG selectively regulates gene expression, we performed differential display screening using cells grown in the presence or absence of HRG. One cDNA clone upregulated by HRG was identical to human calnexin, a protein with molecular chaperone function. This is the first demonstration of the regulation of calnexin mRNA and protein expression by a physiologically relevant polypeptide factor in human breast cancer cells. HRG stimulation also caused a rapid redistribution of calnexin from vesicle-like structures in the cell cytoplasm to the perinuclear area and to the cell membrane. Furthermore, HRG induced colocalization and physical interaction of calnexin with the HER2 growth factor receptor. Finally, calnexin protein levels were increased in progressive stages of human breast cancer. These findings suggest that stimulation of calnexin expression by HRG may constitute a mechanism of protein redistribution and facilitate downstream signaling events in growth-factor-activated cells.
Breast Neoplasms↗
Dynamic chromatin remodeling on the HER2 promoter in human breast cancer cells.
Deregulation of the HER2 oncogene occurs in 30% of human breast cancers and correlates with poor prognosis and increased propensity for metastasis. Since the molecular basis of HER2 overexpression in human cancers is not known, we sought to determine whether chromatin remodeling pathways are involved in the regulation of HER2 expression. We report that compared with breast cancer cells expressing a low level of HER2, HER2-overexpressing breast cancer cells contained significantly higher levels of acetylated and phosphorylated histone H3, and acetylated histone H4 associated with the HER2 promoter. Decreased recruitment of histone deacetylases in the promoter is also noted in the HER2-overexpressing cell. The association of acetylated histone H4 with HER2 gene chromatin and HER2 expression in breast cancer cells was upregulated by an inhibitor of histone deacetylases. Treatment with histone deacetylase inhibitor also reduced the association of histone deacetylase-1 and -2 with the HER2 promoter. In addition, the tumor promoters 12-O-tetradecanoylphorbol-13-acetate and okadaic acid stimulated the association of phosphorylated histone H3 on serine 10 with the HER2 promoter and also stimulated HER2 expression. These findings identify histone acetylation and histone phosphorylation as novel regulatory modifications that target HER2 gene chromatin, and suggest that elevated levels of these chromatin-relaxing components in the vicinity of the HER2 gene promoter may constitute an important non-genomic mechanism of HER2 overexpression in human breast cancer.
Acetylation↗
Asymmetric synthesis of trifluoromethylated allylic amines using alpha,beta-unsaturated N-tert-butanesulfinimines.
[reaction: see text]. The trifluoromethide ion generated in situ from TMSCF(3) and TBAT (tetrabutylammonium triphenyldifluorosilicate), as well as TMAF (tetramethylammonium fluoride), adds to the alpha,beta-unsaturated N-tert-butanesulfinimines exclusively in a 1,2 fashion with high diastereoselectivities, affording the first examples of chiral trifluoromethylated allylic amines.
Journal Article↗
Etk/Bmx tyrosine kinase activates Pak1 and regulates tumorigenicity of breast cancer cells.
Etk/Bmx, a member of the Tec family of nonreceptor protein-tyrosine kinases, is characterized by an N-terminal pleckstrin homology domain and has been shown to be a downstream effector of phosphatidylinositol 3-kinase. P21-activated kinase 1 (Pak1), another well characterized effector of phosphatidylinositol 3-kinase, has been implicated in the progression of breast cancer cells. In this study, we characterized the role of Etk in mammary development and tumorigenesis and explored the functional interactions between Etk and Pak1. We report that Etk expression is developmentally regulated in the mammary gland. Using transient transfection, coimmunoprecipitation and glutathione S-transferase-pull down assays, we showed that Etk directly associates with Pak1 via its N-terminal pleckstrin homology domain and also phosphorylates Pak1 on tyrosine residues. The expression of wild-type Etk in a non-invasive human breast cancer MCF-7 cells significantly increased proliferation and anchorage-independent growth of epithelial cancer cells. Conversely, expression of kinase-inactive mutant Etk-KQ suppressed the proliferation, anchorage-independent growth, and tumorigenicity of human breast cancer MDA-MB435 cells. These results indicate that Pak1 is a target of Etk and that Etk controls the proliferation as well as the anchorage-independent and tumorigenic growth of mammary epithelial cancer cells.
Animals↗
Transcriptional repression of oestrogen receptor by metastasis-associated protein 1 corepressor.
Activation of the heregulin/HER2 pathway in oestrogen receptor (ER)-positive breast-cancer cells leads to suppression of oestrogen-receptor element (ERE)-driven transcription and disruption of oestradiol responsiveness, and thus contributes to progression of tumours to more invasive phenotypes. Here we report the identification of metastatic-associated protein 1 (MTA1), a component of histone deacetylase (HDAC) and nucleosome-remodelling complexes, as a gene product induced by heregulin-beta1 (HRG). Stimulation of cells with HRG is accompanied by suppression of histone acetylation and enhancement of deacetylase activity. MTA1 is also a potent corepressor of ERE transcription, as it blocks the ability of oestradiol to stimulate ER-mediated transcription. The histone-deacetylase inhibitor trichostatin A blocks MTA1-mediated repression of ERE transcription. Furthermore, MTA1 directly interacts with histone deacetylase-1 and -2 and with the activation domain of ER-alpha. Overexpression of MTA1 in breast-cancer cells is accompanied by enhancement of the ability of cells to invade and to grow in an anchorage-independent manner. HRG also promotes interaction of MTA1 with endogenous ER and association of MTA1 or HDAC with ERE-responsive target-gene promoters in vivo. These results identify ER-mediated transcription as a nuclear target of MTA1 and indicate that HDAC complexes associated with the MTA1 corepressor may mediate ER transcriptional repression by HRG.
Acetylation↗
Butyric acid induces apoptosis by up-regulating Bax expression via stimulation of the c-Jun N-terminal kinase/activation protein-1 pathway in human colon cancer cells.
BACKGROUND & AIMS: The colonic epithelial cells near the top of the crypt have been shown to undergo apoptosis. Because butyric acid (BA) is the major short-chain fatty acid produced by fermentation of dietary fiber in the large bowel, it may be an important regulator of apoptosis in colorectal cancer. We investigated which signaling pathway is triggered by BA to undergo apoptosis in human colorectal cancer cells. METHODS: Human DiFi and FET colorectal cells were treated with BA to undergo apoptosis and were assayed for activation of c-Jun N-terminal kinase (JNK), transcription factor activation protein 1 (AP1) and NF-kappaB, and the proapoptotic molecule Bax. The contribution of specific pathways was assessed by examining the effects of dominant-negative mutants of JNK/AP1 or NF-kappaB on BA-induced Bax expression and apoptosis. RESULTS: BA-mediated DNA fragmentation and Bax induction were preceded by early stimulation of JNK, and the DNA-binding activities of AP1 and NF-kappaB. BA-induced enhancement of DNA fragmentation and stimulation of Bax promoter activity were blocked by the expression of dominant-negative mutants of JNK1 or AP1 but not NF-kappaB. CONCLUSIONS: These findings suggest that apoptosis triggered by BA involves transcriptional stimulation of the Bax gene via activation of the JNK/AP1 pathway in colonic epithelial cells.
Apoptosis↗
A study on the activities of a few free radicals scavenging enzymes present in five roadside plants.
The road side plants are continuously exposed to the high levels of oxides of nitrogen and sulphur dioxide, emitted from automobile. Resistance to automobile exhaust pollution was studied with Nerium indicum Mill, Boerhaavia diffusa L., Amaranthus spinosus L., Cephalandra indica Naud., and Tabernaemontana divaricata L., growing on the edges of Delhi Road, National Highway 2 (NH 2) near Dankuni, West Bengal. By analysing the activities of a few enzymes like superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase and phenolic peroxidase, it appears that among the five plants examined,Amaranthus and Cephalandra are equipped with a very good scavenging system to combat effects of air pollution.
Air Pollutants↗
Growth factors regulate heterogeneous nuclear ribonucleoprotein K expression and function.
Epidermal growth factor (EGF) family of growth factors and their receptors regulate normal and cancerous epithelial cell proliferation, a process that can be suppressed by antireceptor blocking antibodies. To identify genes whose expression may be modulated by antireceptor blocking antibodies, we performed a differential display screen with cells grown in the presence or absence of antireceptor blocking antibodies; isolates from one cDNA clone were 100% identical to human heterogeneous nuclear ribonucleoprotein K (hnRNP K), a protein with a conserved KH motif and RGG boxes, has been implicated in such functions as sequence-specific DNA binding, transcription, RNA binding, and nucleocytoplasmic shuttling. Both EGF and heregulin-beta1 induced expression of hnRNP K mRNA and protein in human breast cancer cells. This growth factor-mediated hnRNP K expression was effectively blocked by pretreatment of cultures with humanized anti-EGF receptor (EGFR) antibody C225, or anti-human epidermal growth factor receptor-2 (HER2) antibody. Anti-EGFR monoclonal antibody also caused regression of human tumor xenografts and reduction in hnRNP K levels in athymic mice. Samples from grade III human breast cancer contained more hnRNP K protein than samples from grade II cancer. Finally, overexpression of hnRNP K in breast cancer cells significantly increased target c-myc promoter activity and c-Myc protein, hnRNP K protein levels, and enhanced breast cancer cell proliferation and growth in an anchorage-independent manner. These results suggested that the activity of human EGF receptor family members regulates hnRNP K expression by extracellular growth promoting signals and that therapeutic humanized antibodies against EGFR and HER2 can effectively block this function.
Animals↗
Regulation of elongation factor-1alpha expression by growth factors and anti-receptor blocking antibodies.
The epidermal growth factor (EGF) family and its receptors regulate normal and cancerous epithelial cell proliferation, a process that could be suppressed by anti-receptor blocking antibodies. Polypeptide elongation factor-1alpha (EF-1alpha) is a multifunctional protein whose levels are positively correlated with the proliferative state of cells. To identify genes, whose expression may be modulated by anti-receptor blocking antibodies, we performed a differential display screening and isolated differentially expressed cDNAs. Isolates from one clone were 100% identical to human EF-1alpha. Both EGF and heregulin-beta1 (HRG) induced EF-1alpha promoter activity and mRNA and protein expression. Growth factor-mediated EF-1alpha expression was effectively blocked by pretreatment with humanized anti-EGF receptor antibody C225 or anti-human epidermal growth factor receptor-2 (HER2) antibody herceptin. Mutants and pharmacological inhibitors of p38(MAPK) and MEK, but not phosphatidylinositol 3-kinase, suppressed both constitutive and HRG-induced stimulation of EF-1alpha promoter activity in MCF-7 cells. Deletion analysis of the promoter suggested the requirement of the -393 to -204 region for growth factor-mediated transcription of EF-1alpha. Fine mapping and point mutation studies revealed a role of the SP1 site in the observed HRG-mediated regulation of the EF-1alpha promoter. In addition, we also provide new evidence to suggest that HRG stimulation of the EF-1alpha promoter involves increased physical interactions with acetylated histone H3 and histone H4. These results suggest that regulation of EF-1alpha expression by extracellular signals that function through human EGF receptor family members that are widely deregulated in human cancers and that growth factor regulation of EF-1alpha expression involve histone acetylation.
Acetylation↗
Regulatable expression of p21-activated kinase-1 promotes anchorage-independent growth and abnormal organization of mitotic spindles in human epithelial breast cancer cells.
Stimulation of growth factor signaling has been implicated in the development of invasive phenotypes and the activation of p21-activated kinase (Pak1) in human breast cancer cells (Adam, L., Vadlamudi, R., Kondapaka, S. B., Chernoff, J., Mendelsohn, J., and Kumar, R. (1998) J. Biol. Chem. 273, 28238-28246; Adam, L., Vadlamudi, R., Mandal, M., Chernoff, J., and Kumar, R. (2000) J. Biol. Chem. 275, 12041-12050). To study the role of Pak1 in the regulation of motility and growth of breast epithelial cells, we developed human epithelial MCF-7 clones that overexpressed the kinase-active T423E Pak1 mutant under an inducible tetracycline promoter or that stably expressed the kinase-active H83L,H86L Pak1 mutant, which is deficient in small GTPase binding sites. The expression of both T423E and H83L,H86L Pak1 mutants in breast epithelial cells was accompanied by increased cell motility without any apparent effect on the growth rate of cells. The T423E Pak1 mutant was primarily localized to filopodia, and the H83L,H86L Pak1 mutant was primarily localized to ruffles. Cells expressing T423E Pak1 exhibited a regulatable stimulation of mitogen-activated protein kinase and Jun N-terminal kinase activities. The expression of kinase-active Pak1 mutants significantly stimulated anchorage-independent growth of cells in soft agar in a preferential mitogen-activated protein kinase-sensitive manner. In addition, regulatable expression of kinase-active Pak1 resulted in an abnormal organization of mitotic spindles characterized by appearance of multiple spindle orientations. We also provide evidence to suggest a close correlation between the status of Pak1 kinase activity and base-line invasiveness of human breast cancer cells and breast tumor grades. This study is the first demonstration of Pak1 regulation of anchorage-independent growth, potential Pak1 regulation of invasiveness, and abnormal organization of mitotic spindles of human epithelial breast cancer cells.
Breast Neoplasms↗
A facile stereocontrolled synthesis of anti-alpha-(trifluoromethyl)-beta-amino alcohols.
A short stereocontrolled preparation of anti-alpha-(trifluoromethyl)-beta-amino alcohols is described, involving an initial CF(3) transfer to cinnamaldehyde and a one-step, three-component condensation of 3,3,3-trifluorolactic aldehyde, an alkenyl (aryl) boronic acid, and an amine. Applying this methodology to chiral 3,3,3-trifluorolactic aldehyde allowed us to generate an amino alcohol enantioselectively in 92% ee.
Acrolein↗