Green tea, red wine and lemon extracts reduce experimental tumor growth and cancer drug toxicity.

AIM: To evaluate antitumor effect of plant polyphenol extracts from green tea, red wine lees and/or lemon peel alone and in combination with antitumor drugs on the growth of different transplanted tumors in experimental animals. MATERIALS AND METHODS: Green tea extract (GTE) was prepared from green tea infusion. GTE-based composites of red wine (GTRW), lemon peel (GTRWL) and/or NanoGTE as well as corresponding nanocomposites were prepared. The total polyphenolics of the different GTE-based extracts ranged from 18.0% to 21.3%. The effects of GTE-based extracts were studied in sarcoma 180, Ehrlich carcinoma, B16 melanoma, Ca755 mammary carcinoma, P388 leukemia, L1210 leukemia, and Guerin carcinoma (original, cisplatin-resistant and doxorubicin-resistant variants). The extracts were administered as 0.1% solution in drinking water (0.6-1.0 mg by total polyphenolics per mouse per day and 4.0-6.3 mg per rat per day). RESULTS: Tumor growth inhibition (TGI) in mice treated with NanoGTE, cisplatin or cisplatin + NanoGTE was 27%, 55% and 78%, respectively, in Sarcoma 180%, 21%, 45% and 59%, respectively, in Ehrlich carcinoma; and 8%, 13% and 38%, respectively in B16 melanoma. Composites of NanoGTE, red wine, and lemon peel (NanoGTRWL) enhanced the antitumor effects of cyclophosphamide in mice with Ca755 mammary carcinoma. The treatment with combination of NanoGTE and inhibitors of polyamines (PA) synthesis (DFMO + MGBG) resulted in significant TGI of P388 leukemia (up to 71%) and L1210 leukemia. In rats transplanted with Guerin carcinoma (parental strain), treatment with GTRW or GTE alone resulted in 25-28% TGI vs. 55-68% TGI in cisplatin-treated animals. The inhibition observed in the case of combination of GTE or GTRW with cisplatin was additive giving 81-88% TGI. Similar effects were observed when combinations of the cytostatics with GTE (or NanoGTE) were tested against cisplatin- or doxorubicin-resistant Guerin carcinoma. Moreover, the plant extracts lowered side toxicity of the drugs. Treatment with GTE, NanoGTE, and NanoGTRW decreased the levels of malondialdehyde in heart, kidney and liver tissue of experimental animals, as well as the levels of urea and creatinine in blood serum, increased erythrocyte and platelet counts, hemoglobin content, and decreased leucocyte counts. CONCLUSION: The obtained data indicate the prospects for further development of GTE and corresponding nanocomposites as auxiliary agents in cancer chemotherapy.

Effect of polyamine metabolism inhibitors on Lewis lung carcinoma growth and metastasis.

AIM: To study the influence of polyamine metabolism inhibitors on the growth, metastasis and ornithine decarboxylase (ODC) activity of Lewis lung carcinoma. MATERIALS AND METHODS: Experiments were performed on female mice C57Bl/6 with Lewis lung carcinoma. Nω-hydroxy-nor-arginine (nor-NOHA) and α-difluoromethylornithine (DFMO) were used as arginase and ODC inhibitors, correspondently. Inhibition of tumor growth was calculated by comparison of tumor volume in the treated and control groups. The average number of metastases per animal in the group and the average volume of pulmonary metastases per animal in the group have been determined. Determination of ODC - the key enzyme of the polyamine synthesis - in the samples of experimental tumors was performed by method of Luqman S. RESULTS: Administration of DFMO or it's combination with nor-NOHA resulted in the decrease of tumor growth rate, number and volume of lung metastases and was accompanied with reduced ODC activity in tumor tissue. CONCLUSION: Modifiers of polyamine metabolism may be considered as promising targeted cancer therapy.

Anticancer substances of mushroom origin.

The present status of investigations about the anticancer activity which is inherent to medicinal mushrooms, as well as their biomedical potential and future prospects are discussed. Mushroom products and extracts possess promising immunomodulating and anticancer effects, so the main biologically active substances of mushrooms responsible for immunomodulation and direct cytoto-xicity toward cancer cell lines (including rarely mentioned groups of anticancer mushroom proteins), and the mechanisms of their antitumor action were analyzed. The existing to date clinical trials of mushroom substances are mentioned. Mushroom anticancer extracts, obtained by the different solvents, are outlined. Modern approaches of cancer treatment with implication of mushroom products, including DNA vaccinotherapy with mushroom immunomodulatory adjuvants, creation of prodrugs with mushroom lectins that can recognize glycoconjugates on the cancer cell surface, development of nanovectors etc. are discussed. The future prospects of mushroom anticancer substances application, including chemical modification of polysaccharides and terpenoids, gene engineering of proteins, and implementation of vaccines are reviewed.

Glycopeptide vaccine on DNA-histone carrier and its impact on Z-potential of effector cells during experimental treatment of lymphoblastic leukemia.

AIM: To increase the effectiveness of anticancer vaccine delivery and activity via its immobilization on reconstructed chromatin (RC). MATERIALS AND METHODS: The hybrid mice of CDF-1 line with transplanted P-388 leukemia were used. Reconstructed chromatin was obtained from the thymus of inbred rats. Glycopeptide cancer vaccine prepared from P-388 leukemia cells, was immobilized of RC. ζ-potential of thymocytes from tumor-bearing mice was calculated from Smoluchowski equation. RESULTS: The data have demonstrated the principal possibility of using the fragments of reconstructed chromatin of heterologous origin as a carrier of glycopeptide cancer vaccine prepared from the cells of P-388 leukemia. Preventive immunization with the correspondingly immobilized vaccine normalized ζ-potential of thymocytes in animals with transplanted P­388 leukemia. CONCLUSIONS: The use of immobilization of glycopeptide cancer vaccine on reconstructed chromatin improves anticancer activity of the vaccination.

Ribonucleases in tumor growth.

This review summarizes data on ambiguous biological functions of ribonucleases (RNases) at tumor growth. In some cases the raised level of enzyme activity in biological fluids can be regarded as an additional marker of malignant growth (pancreas cancer, chronic myeloid leukemia, etc.). At the same time the activity of RNases is often lowered in tumor tissue. High substrate specificity of particular RNases provides metabolic balance between various kinds of RNAs with various half-time exchange turn. RNases are the important factors of epigenetic regulation of gene activity in cells. The activity of RNases is adjustable by inhibitors and other factors, and defines time of existence of different kinds of RNAs. RNases (the modified variants of RNase A, RNases of semen fluid of the cattle, RNase of amphibia oocytes) can be used as anti-tumor therapeutic agents. On the other hand, some inhibitors of RNases of natural or synthetic origin were demonstrated to be perspective drugs that inhibit tumor growth.

Influence of aconitine-containing herbal extract BC1 on proliferative and electrokinetic characteristics of endothelial cells.

AIM: To evaluate the influence of new antitumor preparation BC1 produced on the base of Aconitum species on viability and electrokinetic properties of endothelial cells for estimation of mechanisms of its antitumor and antimetastatic activity. MATERIALS AND METHODS: Cytotoxic/cytostatic action of BC1 toward murine aorta endothelial cells (MAEC) and tumor LLC/R9 cells was studied using MTT-test. Apoptotic rate of MAEC was performed by flow cytometry. Electrokinetic properties of MAEC were determined by linear rate of their migration in electric field with the voltage of 20 V/cm. RESULTS: After 24 h of incubation with BC1, IC50 for actively proliferating was 0.95 -/+ 0.06 microg/ml and was 9-fold and 14-fold lower (p < 0.05) than that index for confluent endotheliocytes and LLC/R9 cells respectively. The ability of BC1 to alter electrokinetic characteristics of MAEC and to induce apoptosis has been demonstrated. At the concentration of IC50/10, 1 caused 2-fold decrease of zeta-potential and surface density of charge of compared to the control (p < 0.05) whilst at the concentration of IC50/20 - inversion of surface charge of the majority (80%) of the cells in association with BC1-induced apoptosis. CONCLUSION: High sensitivity of actively proliferating MAEC to the action of BC1 was revealed as well as the ability of that preparation to cause apoptosis and inversion of surface charge of endothelial cells.

Redox-dependent activation of 5'-nucleotidase in rat liver plasma membranes.

Addition of NADH, but not NAD+ or NADPH, to rat liver plasma membranes resulted in the increase of their 5'-nucleotidase activity. NADH-dependent activation of 5'-nucleotidase was significantly suppressed by atebrine, an inhibitor of NADH dehydrogenase of plasma membranes, and completely abolished by 2,4-dinitrophenol (2 X 10(-4)M) and Triton X-100 (2%). Inhibitors of electron transfer in the mitochondrial respiratory chain, rotenone and potassium cyanide, failed to affect 5'-nucleotidase activity in both the presence and absence of NADH. The data obtained give reasons to suggest a redox-dependent mechanism of 5'-nucleotidase activation in rat liver plasma membranes.