OBJECTIVETo investigate the effect of total flavonoids of Hedysarum polybotry on the proliferation, cell cycle, and expressions of p21(Ras) and proliferating cell nuclear antigen (PCNA) gene in erythroleukemia cell line K562.

METHODSThe effect of total flavonoids of Hedysarum polybotry on K562 cell line survival was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) reduction assay. The time- and dose-dependent manner was also observed. The cell cycle and apoptosis were analyzed with flow cytometry (FCM). The immunocytochemistry method was applied to quantitatively analyze the effects of flavonoids of Hedysarum polybotry on changes p21(Ras) and PCNA gene expressions.

RESULTSFlavonoids of Hedysarum polybotry (20-100 μg/mL) significantly inhibited the proliferation of K562 cells in a time- and dose-dependent manner. After K562 cells were cultured for 48 h, total flavonoids of Hedysarum polybotry had no significant effect on the apoptosis of K562 cells but showed significantly inhibition (P<0.01), indicating that total flavonoids of Hedysarum polybotry could induce K562 cells arrested at G(0)/G(1) and G(2)/M phases. Compared with the control group, p21(Ras) and PCNA gene expressions were decreased significantly in K562 cells treated with total flavonoids of Hedysarum polybotry (40 and 80 μg/mL, respectively) for 48 h.

CONCLUSIONThe inhibitory effect on proliferation of K562 cells was observed in the groups treated with flavonoids of Hedysarum polybotry, which might be related to cells arresting.

Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Flavonoids ; pharmacology ; Gene Expression Regulation, Leukemic ; drug effects ; Humans ; K562 Cells ; Leukemia, Erythroblastic, Acute ; drug therapy ; genetics ; pathology ; Oncogene Protein p21(ras) ; genetics ; Proliferating Cell Nuclear Antigen ; genetics ; Ranunculaceae ; chemistry

AML relapsing as ALL has rarely been reported. We describe the case of a 62-yr-old man who was diagnosed with erythroleukemia with a complex karyotype and achieved complete hematologic and cytogenetic remission after induction chemotherapy. However, 4 months after the initial diagnosis, he showed relapse with blasts showing a different morphology and immunophenotype and was diagnosed with precursor B-cell ALL. The relapsing precursor B-cell ALL presented with the same leukemic clones as the primary erythroleukemia. Cytogenetic analysis of his bone marrow (BM) at the time of the primary erythroleukemia showed complex karyotypic abnormalities, including monosomy 5 and monosomy 7. At relapse, his BM showed reemergence of these leukemic clones of complex karyotypic abnormalities with clonal switch. To our knowledge, this is the first case of a lineage switch from erythroleukemia to ALL.
Acute Disease ; Antimetabolites, Antineoplastic/therapeutic use ; Bone Marrow Cells/pathology ; Cell Lineage ; Cell Transformation, Neoplastic ; Chromosome Deletion ; Chromosomes, Human, Pair 5 ; Chromosomes, Human, Pair 7 ; Cytarabine/therapeutic use ; Drug Therapy, Combination ; Humans ; Immunophenotyping ; Karyotyping ; Leukemia, Erythroblastic, Acute/*diagnosis/drug therapy ; Male ; Middle Aged ; Monosomy ; Naphthacenes/therapeutic use ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/pathology ; Recurrence

OBJECTIVETo explore the mechanism of matrine (Mat) induced human erythroleukemia TF-1 cell apoptosis and its effect on SALL4 expression.

METHODDifferent concentrations of the Mat (0.5, 1.0, 1.5, 2.0 g x L(-1) ) were cultured in vitro in TF-1 cells at different time (24, 48, 72 h). Cell proliferation was assayed by MTT. Cell cycle was determined by flow cytometry (FCM). Cell apoptosis was detected by Annexin V and PI double staining method. SALL4 mRNA expression was detected by reverse transcription RT-PCR (RTT-PCR).

RESULTAdministrated with Mat (0.5-2.0 g x L(-1)) after 24, 48, 72 h, the proliferation of TF-1 cells were inhibited (P < 0.01) , and in dose- and time-dependent manner. Half inhibitory concentration (IC50 ) was 1.0 g L(-1) at 48 h. After 48 h that the Mat acted on TF-1 cells, the proportion of G0/G1 phase cells increased while compared with the control group, and S phase cells decreased (P < 0.01). Apoptosis were 8.6% , 11.21%, 15.26% , 17.63%, which showed statistically significant difference (P < 0.01) compared with the control group (5.05%). RT-PCR results showed the ratio between SALL4 mRNA expression and beta-actin (internal reference) expression significantly decreased (P < 0.01) with Mat dose increased.

CONCLUSIONIn a certain range of concentration and time, Mat can inhibit TFT-1 cells proliferation. The mechanism is to make the cells G0/G1 phase blocked, to inhibit SALL4 gene expression and induce cell apoptosis.

Alkaloids ; pharmacology ; Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Gene Expression ; drug effects ; Humans ; Leukemia, Erythroblastic, Acute ; drug therapy ; genetics ; metabolism ; physiopathology ; Quinolizines ; pharmacology ; Transcription Factors ; genetics ; metabolism

Tanshinone II-A is a derivative of phenanthrene-quinone isolated from Salvia miltiorrhiza BUNGE, a traditional herbal medicine that is known to induce antiinflammatory, anti-oxidative and cytotoxic activity. We have examined cellular effects of Tanshione II-A on HL60 human promyelocytic leukemic cells and K562 human erythroleukemic cells. Tanshione II-A induced a dose- and time-dependent DNA fragmentation into the multiples of 180 bp and specific proteolytic cleavage of poly(ADP-ribose) polymerase in both cell lines. PI-staining and flow cytometry analysis of K562 cells following Tanshione II-A treatment showed an increase of the cells possessing hypodiploid DNA indicative of apoptotic state of cells. Caspase-3 activity was significantly increased during Tanshinone II-A treatment of both HL60 and K562 cells, whereas caspase-1 activity was not changed. These results suggest that Tanshione II-A induced HL60 and K562 cellular apoptosis that may be associated with the selective members of caspase family. Copyright 2000 Academic Press.
Antineoplastic Agents, Phytogenic/pharmacology* ; Antineoplastic Agents, Phytogenic/chemistry ; Apoptosis/physiology* ; Caspases/metabolism* ; Caspases/drug effects* ; Cell Cycle/drug effects ; DNA Fragmentation/drug effects ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal/pharmacology* ; Drugs, Chinese Herbal/chemistry ; Enzyme Activation/drug effects ; HL-60 Cells/pathology ; HL-60 Cells/metabolism ; HL-60 Cells/drug effects ; Human ; Lamiaceae/chemistry ; Leukemia/pathology* ; Leukemia/metabolism ; Leukemia/drug therapy ; Leukemia, Erythroblastic, Acute/pathology ; Leukemia, Erythroblastic, Acute/metabolism ; Leukemia, Erythroblastic, Acute/drug therapy ; Phenanthrenes/pharmacology* ; Phenanthrenes/chemistry ; Tumor Cells, Cultured

Pulmonary alveolar proteinosis is a rare disease, which hallmark is a dense accumulation of PAS positive phospholipid material within alveolar sac. Pulmonary alveolar proteinosis is classified as primary form of unknown etiology and secondary form associated with other diseases. We report a case of secondary pulmonary alveolar proteinosis associated with acute erythroleukemia. A C year old male patient complained of nonproductive cough and general weakness, and presented fine inspiratory crackles at both lower lung field. Chest radiographs and high resolution CT scans showd a lobular pattern of ground-grass opacity with interlobular septal thickening in the center field of the both lungs, Bone marrow aspiration and biopsy revealed acute erythroleukemia. Open lung biopsy revealed PAS positive eosinophilic granular material filled in alveoli. He was treated with TAD chemotherapy, but died from multiorgan failure with pneumonia 22days after chemotherapy.
Biopsy ; Bone Marrow ; Cough ; Drug Therapy ; Eosinophils ; Humans ; Leukemia, Erythroblastic, Acute* ; Lung ; Male ; Pneumonia ; Pulmonary Alveolar Proteinosis* ; Radiography, Thoracic ; Rare Diseases ; Respiratory Sounds ; Tomography, X-Ray Computed

A 13 years old girl came to our department with complaints of multiple ulcerating and non-ulcerating nodules on her back and buttocks since 1 month prior to visit. Skin biopsy specimen showed diffuse monomorphous infiltration of leukemic cells in the dermis and subcutis. Bone marrow biopsy specimen showed changes of erythroleukemia. Treatment was initiated with combined chemotherapy which was a combination of cytosine arabinoside, adriamyein and 6 thioguanine. When combined chemotherapy was finished, she was in complete remission state and the nodules cured after 1 month of combined chemotherapy.
Adolescent ; Biopsy ; Bone Marrow ; Buttocks ; Cytarabine ; Dermis ; Drug Therapy ; Female ; Humans ; Leukemia* ; Leukemia, Erythroblastic, Acute* ; Skin ; Thioguanine ; Ulcer