Mode of photoexcited C fullerene involvement in potentiating cisplatin toxicity against drug-resistant L1210 cells.

C fullerene has received great attention as a candidate for biomedical applications. Due to unique structure and properties, C fullerene nanoparticles are supposed to be useful in drug delivery, photodynamic therapy (PDT) of cancer, and reversion of tumor cells' multidrug resistance. The aim of this study was to elucidate the possible molecular mechanisms involved in photoexcited C fullerene-dependent enhancement of cisplatin toxicity against leukemic cells resistant to cisplatin.

Toxicity of C fullerene-cisplatin nanocomplex against Lewis lung carcinoma cells.

Cisplatin (Cis-Pt) is the cytotoxic agent widely used against tumors of various origin, but its therapeutic efficiency is substantially limited by a non-selective effect and high toxicity. Conjugation of Cis-Pt with nanocarriers is thought to be one option to enable drug targeting. The aim of this study was to estimate toxic effects of the nanocomplex formed by noncovalent interaction of C fullerene with Cis-Pt against Lewis lung carcinoma (LLC) cells in comparison with free drug.

C Fullerene Effects on Diphenyl-N-(trichloroacetyl)-amidophosphate Interaction with DNA In Silico and Its Cytotoxic Activity Against Human Leukemic Cell Line In Vitro.

New representative of carbacylamidophosphates - diphenyl-N-(trichloroacetyl)-amidophosphate (HL), which contains two phenoxy substituents near the phosphoryl group, was synthesized, identified by elemental analysis and IR and NMR spectroscopy, and tested as a cytotoxic agent itself and in combination with C fullerene.According to molecular simulation results, C fullerene and HL could interact with DNA and form a rigid complex stabilized by stacking interactions of HL phenyl groups with C fullerene and DNA G nucleotide, as well as by interactions of HL CCl group by ion-π bonds with C molecule and by electrostatic bonds with DNA G nucleotide.With the use of MTT test, the cytotoxic activity of HL against human leukemic CCRF-CM cells with IC value detected at 10 μM concentration at 72 h of cells treatment was shown.

Cytotoxic Effects of Dimorfolido-N-Trichloroacetylphosphorylamide and Dimorfolido-N-Benzoylphosphorylamide in Combination with C Fullerene on Leukemic Cells and Docking Study of Their Interaction with DNA.

Dimorfolido-N-trichloroacetylphosphorylamide (HL1) and dimorfolido-N-benzoylphosphorylamide (HL2) as representatives of carbacylamidophosphates were synthesized and identified by the methods of IR, H, and P NMR spectroscopy. In vitro HL1 and HL2 at 1 mM concentration caused cell specific and time-dependent decrease of leukemic cell viability. Compounds caused the similar gradual decrease of Jurkat cells viability at 72 h (by 35%).

Fullerene C Penetration into Leukemic Cells and Its Photoinduced Cytotoxic Effects.

Fullerene C as a representative of carbon nanocompounds is suggested to be promising agent for application in photodynamic therapy due to its unique physicochemical properties. The goal of this study was to estimate the accumulation of fullerene C in leukemic cells and to investigate its phototoxic effect on parental and resistant to cisplatin leukemic cells. Stable homogeneous water colloid solution of pristine C with average 50-nm diameter of nanoparticles was used in experiments.

Photocytotoxic effect of C60 fullerene against L1210 leukemic cells is accompanied by enhanced nitric oxide production and p38 MAPK activation.

Aim: To estimate the combined action of C60 fullerene and light irradiation on viability of L1210 leukemic cells, nitric oxide (NO) generation, p38 mitogen-activated protein kinase (MAPK) activity and cell cycle distribution.

Methods: Cell viability was assessed by MTT test. Light-emitting diode lamp (λ = 410-700 nm, 2.

COMPUTER PREDICTION OF BIOLOGICAL ACTIVITY OF DIMETHYL-N-(BENZOYL)AMIDOPHOSPHATE AND DIMETHYL-N-(PHENYLSULFONYL)AMIDOPHOSPHATE, EVALUATION OF THEIR CYTOTOXIC ACTIVITY AGAINST LEUKEMIC CELLS IN VITRO.

Structural analogues of β-diketones--dimethyl-N-(benzoyl)amidophosphate (HCP) and dimethyl-N-(phenylsulfonyl)amidophosphate (HSP) were synthesized and identified by the methods of IR, 1H and 31P NMR spectroscopy. Screening of biological activity and calculation of physicochemical parameters of HCP and HSP compounds were done with the use of PASS and ACD/Labs computer programs. A wide range of biological activity of synthesized compounds, antitumor activity in particular, has been found.

Modulation of cisplatin-induced reactive oxygen species production by fullerene C(60) in normal and transformed lymphoid cells.

The early response of normal (Wistar rat thymocytes) and transformed (mice lymphoid leukemia L1210) cells to treatment with anticancer drug cisplatin or to combined treatment with cisplatin and carbon nanostructure fullerene C60 was studied. We demonstrated with fluorescent probes DCFH-DA and TMRE that cisplatin at concentration 1 μg/ml induced reactive oxygen species (ROS) production and decreased the value of mitochondrial membrane potential in both cell types. The combined treatment with cisplatin (1 μg/ml) and fullerene C60 (7.

Enhanced cytotoxicity of photoexcited fullerene C60 and cisplatin combination against drug-resistant leukemic cells.

Aim: To evaluate the viability of leukemic cells sensitive (L1210S) and resistant (L1210R) to cisplatin, ROS production and free cytosolic Ca(2+) concentration under treatment with cisplatin or its combination with photoexcited fullerene C60.

Methods: Cell viability was assessed by the MTT reduction assay. Light-emitting diode lamp (2.

C60 fullerene as synergistic agent in tumor-inhibitory Doxorubicin treatment.

Background: Doxorubicin (Dox) is one of the most potent anticancer drugs, but its successful use is hampered by high toxicity caused mainly by generation of reactive oxygen species. One approach to protect against Dox-dependent chemical insult is combined use of the cytostatic drug with antioxidants. C60 fullerene has a nanostructure with both antioxidant and antitumor potential and may be useful in modulating cell responses to Dox.

Photoactivated fullerene C60 induces store-operated Ca2 entry and cytochrome c release in Jurkat cells.

The values of endoplasmic reticulum Ca(2+)-pool and store-operated Ca2+ entry (SOCE) were estimated in rat thymocytes and Jurkat cells loaded with indo-1 and treated with thapsigargin. It was shown that the relative value of SOCE in thymocytes was substantially lower than in Jurkat cells. Significant increase of SOCE in Jurkat cells preincubated with 10(-5) M C60 and exposed to uv/visible light irradiation was detected at 1-3 h after exposure.

Apoptosis photoinduction by C60 fullerene in human leukemic T cells.

The viability of normal (Wistar rat thymocytes) and transformed (human leukemia Jurkat cells) T cells after UV/Vis irradiation in the presence of pristine C60 fullerene was studied. The data obtained have shown that C60 fullerene exhibits cytotoxic effect against transformed T lymphocytes when combined with UV/Vis irradiation using mercury-vapor lamp (320-600 nm). C60 fullerene photocytotoxicity was not detected in thymocytes.

Using water-soluble C fullerenes in anticancer therapy.

Growth experiments of transplanted malignant tumors in the presence of water-soluble C fullerenes were performed on groups of mice. It was found that C fullerenes efficiently inhibit the growth of transplanted malignant tumors. This behavior can be explained through their high antioxidant activity and the blocking of the specific cell receptors (for example, endothelial growth factor).

Photoinduced cytotoxic effect of fullerenes C60 on transformed T-lymphocytes.

Aim: To estimate the viability of normal and transformed T-lymphocytes after UV/Vis irradiation in the presence of pristine fullerenes C(60).

Methods: Thymocytes were isolated from Wistar rats' thymus. Murine leukemia L1210 and human lymphoma Jurkat cells were used in this study.

Therapeutic reactive oxygen generation.

An increase of the intracellular reactive oxygen species (ROS) concentration leads to the development of oxidative stress and, thus, to the damage of cell components. The cause-and-effect relations between these processes have not been fully established yet. The ability of photo excited supramolecular composites containing fullerenes C60 immobilized at nanosilica particles to generate reactive oxygen species (ROS) in cells of two types (rat thymocytes, and transformed cells of ascite Erlich carcinoma, EAC, and leucosis L1210) is demonstrated.