OBJECTIVETo study the effect of chromomycin A(2) in inducing apoptosis of HepG2 cells and explore the molecular mechanism.

METHODSHepG2, 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.

RESULTSChromomycin 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.

CONCLUSIONIncreased ROS and mitochondria damage may importantly contribute to chromomycin A(2)-induced apoptosis in HepG2 cells.

Apoptosis ; drug effects ; Cell Survival ; Hep G2 Cells ; drug effects ; Humans ; Membrane Potential, Mitochondrial ; Mitochondria ; pathology ; Plicamycin ; analogs & derivatives ; pharmacology ; Reactive Oxygen Species ; metabolism

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.
Anorexia ; Avena ; Breast ; Breast Neoplasms ; Calcitonin ; Calcium ; Diuretics ; Drug Therapy ; Humans ; Hypercalcemia ; Incidence ; Lung ; Lung Neoplasms ; Mortality ; Neoplasm Metastasis ; Neoplasms, Squamous Cell ; Plicamycin ; Prognosis ; Quality of Life ; Stomach ; Stomach Neoplasms ; Stupor