Nanocomplex of Berberine with C Fullerene Is a Potent Suppressor of Lewis Lung Carcinoma Cells Invasion In Vitro and Metastatic Activity In Vivo.

Effective targeting of metastasis is considered the main problem in cancer therapy. The development of herbal alkaloid Berberine (Ber)-based anticancer drugs is limited due to Ber' low effective concentration, poor membrane permeability, and short plasma half-life. To overcome these limitations, we used Ber noncovalently bound to C fullerene (C).

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.

C Fullerene as an Effective Nanoplatform of Alkaloid Berberine Delivery into Leukemic Cells.

A herbal alkaloid Berberine (Ber), used for centuries in Ayurvedic, Chinese, Middle-Eastern, and native American folk medicines, is nowadays proved to function as a safe anticancer agent. Yet, its poor water solubility, stability, and bioavailability hinder clinical application. In this study, we have explored a nanosized carbon nanoparticle-C fullerene (C)-for optimized Ber delivery into leukemic cells.

Synergy of Chemo- and Photodynamic Therapies with C Fullerene-Doxorubicin Nanocomplex.

A nanosized drug complex was explored to improve the efficiency of cancer chemotherapy, complementing it with nanodelivery and photodynamic therapy. For this, nanomolar amounts of a non-covalent nanocomplex of Doxorubicin (Dox) with carbon nanoparticle C fullerene (C) were applied in 1:1 and 2:1 molar ratio, exploiting C both as a drug-carrier and as a photosensitizer. The fluorescence microscopy analysis of human leukemic CCRF-CEM cells, in vitro cancer model, treated with nanocomplexes showed Dox's nuclear and C's extranuclear localization.

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.

Correction to: Complexation with C Fullerene Increases Doxorubicin Efficiency against Leukemic Cells In Vitro.

Following publication of the original article [1], the authors flagged that there was unfortunately an error with Fig. 3 of the article.

Complexation with C Fullerene Increases Doxorubicin Efficiency against Leukemic Cells In Vitro.

Conventional anticancer chemotherapy is limited because of severe side effects as well as a quickly evolving multidrug resistance of the tumor cells. To address this problem, we have explored a C fullerene-based nanosized system as a carrier for anticancer drugs for an optimized drug delivery to leukemic cells.Here, we studied the physicochemical properties and anticancer activity of C fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin.

HPLC-ESI-MS method for C fullerene mitochondrial content quantification.

The presented dataset describes the quantification of carbon nanoparticle C fullerene accumulated in mitochondria of human leukemic cells treated with nanostructure. Firstly, the high performance liquid chromatography-electro spray ionization-mass spectrometry (HPLC-ESI-MS) method was developed for quantitative analysis of pristine C fullerene. Then, human leukemic cells were incubated with C fullerene, homogenized and subjected to the differential centrifugation to retrieve mitochondrial fraction.

C fullerene accumulation in human leukemic cells and perspectives of LED-mediated photodynamic therapy.

Recent progress in nanobiotechnology has attracted interest to a biomedical application of the carbon nanostructure C fullerene since it possesses a unique structure and versatile biological activity. C fullerene potential application in the frame of cancer photodynamic therapy (PDT) relies on rapid development of new light sources as well as on better understanding of the fullerene interaction with cells. The aim of this study was to analyze C fullerene effects on human leukemic cells (CCRF-CEM) in combination with high power single chip light-emitting diodes (LEDs) light irradiation of different wavelengths: ultraviolet (UV, 365 nm), violet (405 nm), green (515 nm) and red (632 nm).

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.

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.

[Generation of active oxygen forms in rat thymocytes under action of hydrogen peroxide and fullerene C60].

The dynamics of active oxygen forms (AOF) generation in rat thymocytes 50 min after treatment with 0.1 and 0.5 mM H2O2 was estimated with the use of fluorescent probe DCFDA.

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.

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.

[Change in concentration of cytosolic Ca2+ caused by extracellular ATP and ecto-ATP-ase activity in thymocytes and transformed MT-4 cells].

The comparative study of extracellular ATP (ATP0) effect on free cytosolic calcium concentration ([Ca2+]i) in normal (isolated rat thymocytes) and transformed (leukosis MT-4 line) T-cells was carried out. Addition of 1 mM ATP to Ca-free incubation medium of both types of cells, loaded with indo-1, had no effect on [Ca2+]i level. Upon subsequent addition of 1 mM CaCl2 to the incubation medium the rapid and significant increase of [Ca2+]i in MT-4 cells was registered.

[Change in glutathione content in rat thymocytes under apoptosis induced by H2O2 or irradiation].

Glutathione (GSH) content as well as GSH-peroxidase and GSH-reductase activity in isolated rat thymocytes X-irradiated in a dose of 4.5 Gy or treated with 0.1 mM H2O2 were studied in a period preceding the appearance of apoptosis morphological symptoms.

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.

[Oxidative properties of photoexcited fullerenes C60 and C60-containing composites in suspension of thymocytes and Ehrlich ascites carcinoma cells].

Biological effects of photoexcited in UV/VIS region water-soluble fullerenes C60 and synthesized C60-containing composites after its addition to cell incubation medium are studied. It is shown by EPR method, that in the presence of photoexcited C60 (10(-5) M) reactive oxygen species (ROS) are generated both in water solution and cell suspensions. ROS generation is accelerated if C60 is included into aminopropylaerosyl or antracenaliminopropylaerosyl.

Effect of the visible light irradiation of fullerene-containing composites on the ROS generation and the viability of tumor cells.

Aim: To study the effect of fullerene-containing composites, irradiated by visible light, on the radical oxygen species (ROS) generation in thymocytes, ascitic cells from Erlich's tumor and leukemia cells L1210; to investigate viability of these cells in the presence of fullerene-containing composites under irradiation conditions.

Materials And Methods: The viability of cells was evaluated by staining with 0.4% solution of the trypan blue; ROS were detected with the use of electron paramagnetic resonance (EPR) spectroscopy and spin traps; solutions of fullerene-containing composites were irradiated with mercury-vapor lamp.