ABSTRACT
We studied cytotoxic activity of new tetranitrosyl NO-generating binuclear iron-sulfur [Fe-S] complexes containing different ligands in the molecule against tumor cells in vitro. Cytotoxic activity of the most active complex with cysteamine (CysAm) was compared with that of antitumor drug cisplatin. Caspase activation and morphological changes in cells were visualized by fluorescence microscopy. Fluorescence of active caspases 3 and 7 and changes in nuclear DNA in cells in the presence of CyAm were detected by using fluorochrome-labeled inhibitor of caspases (FLICA) and Hoechst and propidium iodide reagents. Similar cytotoxic activities of CyAm and cisplatin were demonstrated in various human tumor cell lines of different histogenesis. Therefore, a new class of NO-donating [Fe-S] complexes can provide the base of potential drugs for chemotherapy with a new mechanism of action.
Subject(s)
Antineoplastic Agents/pharmacology , Iron/pharmacology , Nitrogen Oxides/pharmacology , Sulfur/pharmacology , A549 Cells , Antineoplastic Agents/chemistry , Cell Line, Tumor , Drug Screening Assays, Antitumor , Humans , Iron/chemistry , K562 Cells , MCF-7 Cells , Nitrogen Oxides/chemistry , Sulfur/chemistryABSTRACT
We studied specific antitumor activity of a liposomal drug based on tetra-3-phenylthiophthalocyanine aluminum hydroxide (lipophthalocyan) intended for photodynamic therapy. The optimal dose and protocol for photodynamic therapy with lipophthalocyan were chosen in experiments on mice: single intravenous dose of 6 mg/kg with a 5-h interval between administration and laser exposure and irradiation energy density of 400 J/cm2. A wide spectrum antitumor activity of lipophthalocyan was demonstrated in vivo for various transplantable mouse tumors (Lewis lung epidermoid carcinoma, S37 sarcoma, and colon adenocarcinoma AKATOL). The results show the possibility of using lipophthalocyan for photodynamic therapy of tumors of surface localization (skin and mucosa tumors).
Subject(s)
Lasers , Liposomes/chemistry , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Animals , Carcinoma, Lewis Lung/therapy , Colonic Neoplasms/therapy , Female , Male , Mice , Mice, Inbred BALB C , Sarcoma/therapyABSTRACT
We performed an in vivo comparative study of activity of three substances of the nitrosourea group produced in Russia. All substances demonstrated high antitumor activity against various solid and leukemic tumors. Aranosa significantly enhanced life duration in mice with leukemia (by 65-194%) and inhibited the growth of solid tumors (by 49-99.6%). Lisomustine and ormustine showed higher activity than aranose. Single administration of lisomustine increased life span of mice (by 22-114%) and resulted in cure of all animals in four models: lymphoblastic leukemia L-1210, lymphocytic leukemia P-388, Lewis lung carcinoma, and cervical cancer RShM-5. After ormustine treatment, full recovery was observed only in groups with lymphocytic leukemia P-388 and cervical cancer RShM-5. These findings attest to higher activity of lisomustine in the studied models.
Subject(s)
Antineoplastic Agents/therapeutic use , Nitrosourea Compounds/therapeutic use , Animals , Female , Leukemia L1210/drug therapy , Leukemia P388/drug therapy , Male , Mice , Neoplasms, Experimental/drug therapy , Russia , Treatment Outcome , Uterine Cervical Neoplasms/drug therapyABSTRACT
The efficiency of photodynamic therapy with photosensitizer Tiosens (Russia) was evaluated in mono- and combined therapy of rats with malignant gliomas (glioblastoma 101/8, oligodendroglioma 14-4-9, and C6 glioma). The efficiency of photodynamic monotherapy was not high: the animals died from brain edema developing in tumor tissue and in the adjacent normal cerebral tissue. Pathomorphological studies of tumor tissue detected necrosis and apoptosis, destruction of vessels with hemorrhages, and vascular thrombosis. Combined therapy for malignant gliomas including Tiosens photodynamic therapy and subsequent temodal or lysomustine chemotherapy, was the most effective. In glioblastoma 101/8, combined therapy with lysomustine or temodal led to prolongation of the lifespan by 127 %; 62.5 and 50 % rats were cured, respectively; in oligodendroglioma 14-4-9, animal lifespan was prolonged by 80 and 60 %, with 43 and 45 % rats cured, respectively. Glioma C6 was least sensitive to therapy.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Glioblastoma/drug therapy , Oligodendroglioma/drug therapy , Photochemotherapy , Animals , Animals, Outbred Strains , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Dacarbazine/administration & dosage , Dacarbazine/analogs & derivatives , Drug Screening Assays, Antitumor , Humans , Indoles/administration & dosage , Neoplasm Transplantation , Nitrosourea Compounds/administration & dosage , Organometallic Compounds/administration & dosage , Photosensitizing Agents/administration & dosage , Rats, Wistar , TemozolomideABSTRACT
Cytestrole acetate (CA), in the structure of which the steroidal antiestrogen component is associated with bis-ß-cloroethylamino group, exhibits a strong cytotoxic activity against hormone-dependent cancer cell lines (CaOV, HeLa, MCF-7). In doxorubicin-resistant MCF-7 cells, CA potentiates the cytotoxic effect of etoposide and doxorubicin, and the IC50 for CA in these cells is 40 times lower than that for tamoxifen (TAM). In transplantable mice breast adenocarcinoma Ca-755, the therapeutic CA dose is 25 mg/kg when administered subcutaneously in oil solution for 5 days. On the DMBA-induced mammary tumors in rats, CA injected subcutaneously led to partial regressions 4 weeks after treatment in 75% of test rats, whereas TAM produced this effect in 43% of rats. Among various drug forms of CA, the most active were oil solution of CA in gelatin capsules for oral use and liposomal emulsion for intravenous administration, since these forms exhibited the highest values of Ca-755 tumor growth inhibition index (TGI = 97 - 98%).
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Agents, Hormonal/pharmacology , Breast Neoplasms/drug therapy , Cytostatic Agents/pharmacology , Estrogen Antagonists/pharmacology , Ethinyl Estradiol/analogs & derivatives , Adenocarcinoma/pathology , Animals , Breast Neoplasms/pathology , Cell Line, Tumor , Doxorubicin/pharmacology , Drug Administration Schedule , Drug Synergism , Ethinyl Estradiol/pharmacology , Etoposide/pharmacology , Female , Humans , Inhibitory Concentration 50 , Injections, Subcutaneous , Mice , Rats , Tamoxifen/pharmacology , Tumor Burden/drug effects , Xenograft Model Antitumor AssaysABSTRACT
Morphometric and electronmicroscopic studies of the capsule of a clear lens depending on the degree of myopia and age as compared with the capsule of a clear lens in emmetropia and myopia have shown that with age the anterior capsule of a clear lens becomes thicker, while the posterior capsule becomes thinner and increases in length. This is connected with the weakening of accommodation in the presence of different curvature of the anterior and posterior surfaces of the lens on the background of the lowering of the metabolic level in elderly persons. In myopia, with the development of age changes the thickness of the lens capsule remains almost unchanged. The degree of myopia doesn't influence the thickness and the length of the anterior capsule of the lens, while with the rise of myopia the thickness of the posterior capsules increases. No dystrophic changes in the structure of such a capsule in high myopia were revealed. Hypertrophy of the posterior capsule speaks about the increase of its mechanic strength in a clear lens and is connected with the weakness of accommodation. Such a capsule can serve as a support for IOL implants in patients with myopic refraction.