Chromomycin A(2) induces apoptosis of HepG2 cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of chromomycin A(2) in inducing apoptosis of HepG2 cells and explore the molecular mechanism.</p><p><b>METHODS</b>HepG2, MCF-7, A549, and 7901 cells were exposed to chromomycin A(2) and the changes in the cell viability were detected using MTT assay. The changes in the chromatins were observed with laser scanning confocal microscope after incubation of the cells with chromomycin A(2) (60 nmol/L) for 24 h. The changes in cell morphology were examined with a phase-contrast microscope, and the apoptotic cell populations, fluorescent intensity of reactive oxygen species (ROS) and mitochondrial membrane potential were determined using flow cytometry.</p><p><b>RESULTS</b>Chromomycin A(2) significantly inhibited the proliferation of the cells in a time- and dose-dependent manner, and caused changes in the cell morphology and cell apoptosis. Exposure of the cells to chromomycin A(2) resulted in chromatin condensation, ROS generation, and reduction of the mitochondrial membrane potential.</p><p><b>CONCLUSION</b>Increased ROS and mitochondria damage may importantly contribute to chromomycin A(2)-induced apoptosis in HepG2 cells.</p>

Interactions of chromomycin A3 and mithramycin with the sequence d(TAGCTAGCTA)2.

Anti-cancer antibiotics, chromomycin A3 (CHR) and mithramycin (MTR) inhibit DNA directed RNA synthesis in vivo by binding reversibly to template DNA in the minor groove with GC base specificity, in the presence of divalent cations like Mg2+. Under physiological conditions, (drug)2Mg2+ complexes formed by the antibiotics are the potential DNA binding ligands. Structures of CHR and MTR differ in their saccharide residues. Scrutiny of the DNA binding properties reveal significant differences in their sequence selectivity, orientation and stoichiometry of binding. Here, we have analyzed binding and thermodynamic parameters for the interaction of the antibiotics with a model oligonucleotide sequence, d(TAGCTAGCTA)2 to understand the role of sugars. The oligomer contains two potential binding sites (GpC) for the ligands. The study illustrates that the drugs bind differently to the sequence. (MTR)2Mg2+ binds to both sites whereas (CHR)2Mg2+ binds to a single site. UV melting profiles for the decanucleotide saturated with the ligands show that MTR bound oligomer is highly stabilized and melts symmetrically. In contrast, with CHR, loss of symmetry in the oligomer following its association with a single (CHR)2Mg2+ complex molecule leads to a biphasic melting curve. Results have been interpreted in the light of saccharide dependent differences in ligand flexibility between the two antibiotics.

Interaction of mithramycin with chromatin.

Mithramycin (MTR) is an anti-cancer antibiotic that blocks the macromolecular biosynthesis via reversible interaction with DNA template in the presence of bivalent metal ion such as Mg2+. In absence of DNA, mithramycin forms two types of complexes with Mg2+, complex I (with 1:1 stoichiometry in terms of MTR: Mg2+) and complex II (with 1:2 stoichiometry in terms of MTR: Mg2+). In an eukaryotic system, the drug would interact with chromatin, a protein-DNA complex. We have employed the spectroscopic techniques such as absorption and fluorescence to study the interaction of MTR: Mg2+ complexes with rat liver chromatin. In this report, we have shown that the two types of ligands have different binding potentials with the same chromatin. This supports our proposition that complexes I and II, are different molecular species. We have also shown that the histone protein(s) reduce the binding potential and the number of available sites for both ligands.

Hypercalcemia Associated with Bone Metastasis / 대한정형외과학회잡지

Hypercalcemia is a relatively common complication of cancer that is clinically important because, left unattended, it is associated with symptomatic deterioration and even death. So hypercalcemia can afflict the quality of life and complicate management of the cancer patients with anorexia, lethargic, stuporous mentality, and severely dehydrated. Nonetheless, most cancers are at an advanced stage by the time hyperclacemia develops, many clinicians share doubts about the role of antihypercalcemic therapy in this situation. Furthermore, because the symptoms of hypercalcemia may mimic that of progressive malignant disease or the toxic effects of chemotherapy and radiation therapy, this may not always be recognized. So concerns are needed for active management of patients with malignant hypercalcemia. The authors reviewed the morbidity and mortality in 20 patients with malignant hypercalcemia out of 219 patients with bone metastasis, who were treated at the department of orthopaedic surgery, Catholic University Medical College from January 1989 through December 1992. The results were as follows. 1. The overall incidence of malignant hypercalcemia was 8.6% of bone metastases (20 out of 219 cases).: lung cancer 11.2% (10 out of 89 cases), breast cancer 22.5% (7 out of 31 cases), stomach cancer 6.3% (3 out of 47 cases). 2. The underlying diseases associated with hyprecalcemia were 10 cases of lung cancer(50%), 7 cases of breast cancer(35%) and 3 cases of stomach cancer(15%). Out of lung cancers, 8 cases were squamous cell cancers, the other 2 cases were oat cell cancers. 3. Only 7 out of 20 patients were treated with hydration, diuretics, steroid, calcitonin and mithramycin. And the mean survival duration after recognition of hypercalcemia was 11.3 weeks independent of treatment. In conclusion, the authors emphasize that inspite of grave prognosis, when treated actively, calcium lowering therapy may allow patients to be discharged during terminal period of their illness.

Emergências oncológicas mais frequentes na prática clínica / Oncologic emergencies frequency in clinical practice

Os autores fazem uma revisäo bibliográfica, sintetizando de forma clara e concisa os principais aspectos etiológicos e terapêuticos das emergências oncológicas mais frequentemente encontradas na prática clínica diária: hipercalcemia, síndrome da veia cava superior e compressäo medular

Búsquedas de nuevas sustancias antitumorales: VIII evaluación de la afinidad de enlace con el receptor de estradiol uterino de la rata, del aureol y algunos derivados / The search for new antitumoral drugs: VIII assessment of binding affinity with the receptor of rat uterine estradiol, aureol and some derivatives

Se obtuvieron algunos derivados del aureol y se evaluó la capacidad de éstos de competir con el estradiol por enlazarse con el receptor de estradiol de útero de rata. Se comprobó que al igual que el aureol, todos los compuestos desplazan al estradiol; el dibromo aureol es el que presenta mayor afinidad por el receptor y se compara su afinidad con la del antiestrógeno tamoxifén