In the review, the use of the ribonucleases for cancer therapy is discussed. Using of epigenetic mechanisms of regulation — blocking protein synthesis without affecting the DNA structure — is a promising direction in the therapy. The ribonucleases isolated from different sources, despite of similar mechanism of enzymatic reactions, have different biological effects. The use of enzymes isolated from new sources, particularly from plants and fungi, shows promising results. In this article we discuss the new approach for the use of enzymes resistant to inhibitors and ribozymes, that is aimed at the destruction of the oncogene specific mRNA and the induction of apoptosis.
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 doxorubicinresistant 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 N anoGTE) 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 deve lopment of GTE and corresponding nanocomposites as auxiliary agents in cancer chemotherapy.
Summary. Prostate cancer (PCa), the most common solid malignant neoplasm in men, is characterized using the Gleason score and diagnosed using prostate-specific antigen (PSA) biomarker. However, Gleason score and PSA-based diagnostics are not universal and have significant limitations. It is supposed that the ornithine decarboxylase activity (AODC) could be a suitable auxiliary biomarker for the PCa diagnosis or monitoring the therapeutic efficacy. Aim: To assess the relation between AODC in PCa tissues and the level of serum PSA with the Gleason score (GS) and the clinical stage. Materials and Methods: 29 patients (48 to 79 years old) with prostate adenocarcinoma of different GS (6 to 10) and clinical stage (T1 to T4) were enrolled in the study. The AODC was analyzed in the PCa tissues by the modified spectrophotometric assay. Results: The patients with PCa were distributed into two groups: with low AODC < 0.3 and high AODC > 0.45. In group with AODC < 0.3, the highest value of AODC was recorded in patients with the lowest GS (= 6), while in group with AODC > 0.45, the highest value of AODC was recorded in the patients with the highest GS (= 9–10). Furthermore, in group with AODC > 0.45, the highest value of AODC was registered in the patients with T1 or T4 stage. The highest levels of serum PSA were detected in T3–T4 cases and in cases with the highest GS. Conclusion: The patterns of AODC and serum PSA can be used as supplementary indices useful for monitoring PCa course.
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