Sanguinarine, chelerythrine and chelidonine are isoquinoline alkaloids derived from the greater celandine. They possess a broad spectrum of pharmacological activities. It has been shown that their anti-tumor activity is mediated via different mechanisms, which can be promising targets for anti-cancer therapy. We focused our study on the differential effects of these alkaloids upon cell viability, DNA damage effect and nucleus integrity in mouse primary spleen cells and mouse lymphocytic leukemic cells, L1210. Sanguinarine and chelerythrine produce a dose-dependent increase in DNA damage and cytotoxicity in both primary mouse spleen cells and L1210 cells. Chelidonine did not show a significant cytotoxicity or damage DNA in both cell types, but completely arrested growth of L1210 cells. Examination of nuclear morphology revealed more cells with apoptotic features upon treatment with chelerythrine and sanguinarine, but not chelidonine. In contrast to primary mouse spleen cells, L1210 cells showed slightly higher sensitivity to sanguinarine and chelerythrine treatment. This suggests that cytotoxic and DNA damaging effects of chelerythrine and sanguinarine are more selective against mouse leukemic cells and primary mouse spleen cells, whereas chelidonine blocks proliferation of L1210 cells. The action of chelidonine on normal and tumor cells requires further investigation.

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Transforming growth factor beta-1 (TGFbeta-1) is a regulator of cell proliferation, differentiation and apoptosis. Doxorubicin (adriamycin), an anthracycline drug causing double-strand DNA breaks, is widely used in anticancer chemotherapy. Here we demonstrated that TGFbeta-1 enhanced cytotoxic (proapoptotic) action of doxorubicin towards cultured human lung carcinoma A549 cells. Western-blot analysis and immunocytochemistry were used to show that doxorubicin induced PARP degradation in A549 cells, and TGFbeta-1 enhanced that action of the drug. The obtained results suggest a possibility of biomodulating effect of TGFbeta-1 on tumor cell treatment with doxorubicin.

The genetic transformation of target cells is a key tool in modern biological research, as well as in many gene therapy and biotechnology applications. Here we describe a new method for delivery of DNA into several industrially important species of yeast, including Saccharomyces cerevisiae. Our method is based on the use of a novel nanoscale oligoelectrolyte polymer possessing a comb-like structure as a carrier molecule. Direct comparisons to standard transformation methods clearly show that our approach: (i) yields two times more transformants of Hansenula polymorpha NCYC 495 compared to electroporation approaches and 15 times more transformants compared to lithium acetate protocols, as well as (ii) 5 times more Pichia pastoris GS115 transformants compared to electroporation and 79 times more transformants compared to lithium acetate. Taken together, these results clearly indicate genetic transformation of yeasts using oligoelectrolyte polymer carriers is a highly effective means of gene delivery.