homoharringtonine and ungeremine

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

Growth inhibition in the Chinese hamster cell line V79 and in the human lymphoid cell line Raji and induction of sister chromatid exchange(s) (SCE) in V79 cells after treatment with six anticancer drugs [harringtonine (HRT), homoharringtonine (HHRT), camptothecin (CPT), hydroxycamptothecin (HCPT), lycobetaine (LBT), and oxalysine (OXL)] developed in the People's Republic of China were studied. OXL is a new antibiotic; all other drugs are plant extracts. All drugs caused a dose-dependent growth inhibition in both cell types, as evidenced by decreases in plating efficiencies of V79 cells and in viable cell counts of Raji. However, the degree of inhibition differed widely among the drugs. HRT, HHRT, CPT, and HCPT were the most potent growth inhibitors, LBT was next, and OXL was the least effective inhibitor. SCE analyses were made in V79 cells treated with a drug in the presence or absence of the metabolic activation system S9 mixture (S9 mix), except for the HRT assay in which the S9 mix was not used. CPT, HCPT, and LBT induced a dose-dependent increase in SCE frequencies, while HRT, HHRT, and OXL caused no SCE induction at any dose level used. CPT was the most powerful SCE inducer. HCPT induced SCE but at a much reduced rate when compared to that of CPT. LBT was a weak SCE inducer; SCE induction was seen only in cultures treated with 40 micrograms or more LBT/ml. Addition of the S9 mix did not alter SCE frequencies, indicating that the drugs were direct-acting agents. HRT and HHRT were highly toxic, but they induced no increases in SCE frequency, indicating that cytotoxicity of a compound does not necessarily correlate with SCE induction.

Topics: Alkaloids; Amaryllidaceae Alkaloids; Amino Acids, Dicarboxylic; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Camptothecin; Cell Division; Cell Line; China; Cricetinae; Cricetulus; Crossing Over, Genetic; Harringtonines; Homoharringtonine; Humans; Indolizines; Lung; Lymphoid Tissue; Mutagenicity Tests; Serine; Sister Chromatid Exchange

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