Flow Cytometric Analysis of the Cell Cycle of the Leukemic Cell Lines Treated with Etoposide and Cytosine Arabinoside.

Abstract

(2), 95-107 Effects of etoposide (VP-16) and cytosine arabinoside (Ara-C) on the cell cycle of HL-60 and THP-1 cells were studied by flow cytometry using the bromodeoxyuridine (BrdU)/DNA assay technique to investigate the efficacy of VP-16 for monocytic leukemia cells. VP-16 inhibited the proliferation of THP-1 cells more strongly than that of HL-60 cells at any concentrations used at 24 and 48 hr. VP-16 arrested HL-60 and THP-1 cells in the G2 /M phase and reduced them in the Go/G1 and early S phase at higher concentrations. There was no significant difference in the percentage of G2/M phase cells at the same concentration between both cells. However, reduction in the Go/G, and early S phase cells was more marked in THP-1 than HL-60 cells significantly. On the other hand, Ara-C perturbed the cell cycle of HL-60 cells more than that of THP-1 cells at 24 and 48 hr. These results suggest that the effects of VP-16 on the cell cycle may be more intense in THP-1 than HL-60 cells, and support the efficacy of VP-16 for treating monocytic leukemia in vivo. flow cytometry; cell cycle; bromodeoxyuridine (BrdU); etoposide (VP-16); cytosine arabinoside (Ara-C) Etoposide (VP-16), a newly developed semisynthetic derivative of podophyllotoxin (Loike and Horwitz 1976;Roberts et al. 1980), is recently available for the treatment of acute leukemias and malignant lymphomas, and has been found useful for relapsed or refractory cases (Mathe et al. 1974;Bishop et al. 1990). This drug is considered more effective for patients with monocytic leukemia than for those with other types of leukemia (Mathe et al. 1974;Bernasconi et al. 1982;

Culture of human cell lines by a pathogen-inactivated human platelet lysate

“…In fact, it seems that the presence of FBS rendered these cells more sensitive to the drug, likely altering the real capacity of these effectors to induce growth arrest and cell death. Moreover, regarding this aspect, it has been reported that primary leukemic cells showed an S-phase ranging from 20 to 45 %, which is the same range that we found in PL cultures, which may more likely resemble the kinetic behaviour of these primary cells (Ishiyama et al 1994). However, a proper dose-response curve was also observed for cells cultured in PL, indicating a preserved cell sensitivity to the drug, with differences that did not reach statistical significance at any dose-point, except for HL-60 at 0.005 and 0.01 lg/ml (p \ 0.05).…”

Usefulness of PKH fluorescent labelling to study leukemic cell proliferation with various cytostatic drugs or acetyl tetrapeptide – AcSDKP

“…We did not observe any modification of cell cycle distribution in the presence of these drugs. These two drugs were reported as inducing cell accumulation in G2+M [24,25]. …”

The effect of quercetin on oxidative DNA damage and myelosuppression induced by etoposide in bone marrow cells of rats.

“…The second serious side effect caused by etoposide is myelosuppression (Kobayashi & Ratain, 1994), which limits its application and may be a cause of the failure of chemotherapy. Etoposide inhibits proliferation of cells in the G2/M phase of the cell cycle (Ishiyama et al, 1994). The development of bone marrow hypoplasia induced by etoposide could also partially be attributed to the pro-oxidant action of its radicals.…”