homoharringtonine and 10-hydroxycamptothecin

The effects of lycobetaine (LBT) on DNA single strand break and chromatin conformation were examined by in-situ nick translation method. It was found that LBT did not cause DNA single strand break. After 2-h incubation of murine hepatoma cells with 1-50 micrograms/ml LBT in vitro, the chromatin transcription activity was inhibited gradually. This effect was time- and dose-dependent. Actinomycin D produced a similar effect; 10-hydroxycamptothecin not only caused DNA single strand break, but also altered chromatin conformation; homoharringtonine had no marked influence on either. By molecular hybridization technique, it was found that the effect of LBT on individual genes was somewhat different. After 2-h incubation of the cells with LBT, the sensitivities of c-myc, N-ras, and beta 2-microglobulin genes to DNase I were decreased from 75 +/- 6, 66 +/- 4, 70 +/- 8% to 28 +/- 8, 25 +/- 5, 28 +/- 7%, respectively, while that of c-myb and beta-globin genes (8 + 6%, 6 + 5%) did not change obviously.

Topics: Alkaloids; Amaryllidaceae Alkaloids; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Camptothecin; Chromatin; Dactinomycin; DNA Damage; DNA, Neoplasm; Harringtonines; Homoharringtonine; Indolizines; Liver Neoplasms, Experimental; Mice; Oncogenes; Time Factors; Tumor Cells, Cultured

Topics: Alkaloids; Amaryllidaceae Alkaloids; Antineoplastic Agents, Phytogenic; Camptothecin; Colony-Forming Units Assay; Fluorouracil; Harringtonines; Homoharringtonine; Humans; Indolizines; KB Cells; Vincristine

Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Camptothecin; Cattle; Circular Dichroism; Dactinomycin; DNA; Harringtonines; Homoharringtonine; Nucleic Acid Conformation

The influence of homoharringtonine, hydroxycamptothecin and lycobetaine on the cell cycle progression of murine erythroleukemia cells was studied by using flow microfluorometry (FMF) technique and centrifugal elutriation to obtain specific fractions of the cell cycle. FMF histogram analysis showed that homoharringtonine could strongly arrest cells in the G1 phase of the immediate cell cycle. This effect was more pronounced and persisted longer with G1 cells than with S or G2 cells. Hydroxycamptothecin mainly delayed the progression of S cells of the subsequent cell cycle (daughter cells). Lycobetaine caused a marked accumulation of G2 cells. These 3 compounds possess a relatively specific action on cell progression through the cell cycle. Homoharringtonine and hydroxycamptothecin can inhibit the cell proliferation of murine erythroleukemia cells (MELC) at low concentrations (ng/ml) whereas lycobetaine, cantharidin and oxalysine are less potent. Among them only hydroxycamptothecin had a weak activity to induce MELC differentiation. These results may provide some basic knowledge for designing new protocols of the combination treatment of neoplastic diseases.

Topics: Alkaloids; Amaryllidaceae Alkaloids; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Camptothecin; Cell Cycle; Cell Differentiation; Cell Division; Cell Separation; Cells, Cultured; Flow Cytometry; Harringtonines; Homoharringtonine; Indolizines; Leukemia, Erythroblastic, Acute; Mice