mezerein and Leukemia

Since plants are an important source of anticancer drugs, we have carried out a random screening for selective anticancer activity of 57 extracts from 45 plants collected in Grazalema Natural Park, an area in the South of Spain of high plant diversity and endemism. Using lung cancer cells (A549) and lung non-malignant cells (MRC-5), we found that several extracts were more cytotoxic and selective against the cancer cells than the standard anticancer agent cisplatin. Five active extracts were further tested in cancer and normal cell lines from other tissues, including three skin cell lines with increasing degree of malignancy. An extract from the leaves of

Topics: A549 Cells; Antineoplastic Agents; Cell Line; Cell Line, Tumor; Daphne; Diterpenes; Humans; Leukemia; Lung Neoplasms; Plant Extracts; Spain; Thymelaeaceae

Biological assay guided fractionation of a dichloromethane extract of Synaptolepis kirkii led to the isolation of four new and five known daphnane-type diterpene orthoesters, whose structure was established by spectroscopic data. Full spectroscopic data of the new and known natural products are reported here for the first time. Pronounced neurotrophic and substantial antileukaemia activities of these compounds were found in in vitro assays.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Survival; Chick Embryo; Diterpenes; Ganglia, Spinal; Humans; Leukemia; Models, Molecular; Molecular Structure; Nerve Growth Factors; Neurons; Terpenes; Thymelaeaceae; Triterpenes; Tumor Cells, Cultured

Freshly isolated human peripheral blood lymphocytes from leukemia (AML, ALL, CML) subjects, showed a 2.5-3.5-fold increase in the poly ADPR transferase (poly ADPRT) activity whereas ovarian cancers showed a 2-fold increase. This was accompanied by a drop in NAD levels of 45%-63% in leukemia cells and 40% in ovarian cancers. Tumour promoters phorbol-12-myristate-13-acetate (PMA) and mezerein produced an increase in poly ADPRT activity in both normal and CML lymphocytes, but the increase was more marked in the case of normals. This was accompanied by a drop in NAD levels. The results presented show a marked increase in poly ADP-ribosylation in malignant cells but normal lymphocytes showed a greater response to tumour promoters as compared to CML lymphocytes.

Topics: Adolescent; Adult; Biomarkers, Tumor; Carcinogens; Cell Division; Diterpenes; DNA Damage; Female; Humans; Kinetics; Leukemia; Lymphocytes; Middle Aged; NAD; Ovarian Neoplasms; Poly(ADP-ribose) Polymerases; Terpenes; Tetradecanoylphorbol Acetate