Micellar Curcumin Substantially Increases the Antineoplastic Activity of the Alkylphosphocholine Erufosine against TWIST1 Positive Cutaneous T Cell Lymphoma Cell Lines.

Cutaneous T-cell lymphoma (CTCL) is a rare form of cancer with local as well as systemic manifestations. Concomitant bacterial infections increase morbidity and mortality rates due to impaired skin barrier and immune deficiency. In the current study, we demonstrated that the in vitro anti-lymphoma potential of erufosine is diminished by TWIST1 expression and micellar curcumin substantially increases its antineoplastic activity.

In Vitro Antineoplastic and Antiviral Activity and In Vivo Toxicity of L. Extracts.

This study evaluated the in vitro antineoplastic and antiviral potential and in vivo toxicity of twelve extracts with different polarity obtained from the herbaceous perennial plant L. (). In vitro cytotoxicity was determined by ISO 10993-5/2009 on bladder cancer, (T-24 and BC-3C), liver carcinoma (HEP-G2) and normal embryonic kidney (HEK-293) cell lines.

Antineoplastic effect of a novel nanosized curcumin on cutaneous T cell lymphoma.

Cutaneous T cell lymphomas (CTCLs) are a group of heterogeneous, life-threatening, extra-nodal and lymphoproliferative T cell neoplasms. Since chronic inflammation serves a key role in CTCL progression, curcumin, a natural pigment with proven anti-inflammatory and antineoplastic properties, as well as minimal toxicity, may be used as a therapeutic agent. In the present study, two formulations of curcumin (standard ethanolic and a PluronicP-123/F-127 micellar solution) were compared regarding their cytotoxic efficacy and speed of internalization in three CTCL cell lines, namely HuT-78, HH and MJ.

Synthesis, Spectroscopic Properties, Crystal Structure And Biological Evaluation of New Platinum Complexes with 5-methyl-5-(2-thiomethyl)ethyl Hydantoin.

Background: The accidental discovery of Cisplatin's growth-inhibiting properties a few decades ago led to the resurgence of interest in metal-based chemotherapeutics. A number of well-discussed factors such as severe systemic toxicity and unfavourable physicochemical properties further limit the clinical application of the platinating agents. Great efforts have been undertaken in the development of alternative platinum derivatives with an extended antitumor spectrum and amended toxicity profile as compared to the reference drug cisplatin.

Alkylphospholipids are Signal Transduction Modulators with Potential for Anticancer Therapy.

Background: Alkylphospholipids (APLs) are synthetically derived from cell membrane components, which they target and thus modify cellular signalling and cause diverse effects. This study reviews the mechanism of action of anticancer, antiprotozoal, antibacterial and antiviral activities of ALPs, as well as their clinical use.

Methods: A literature search was used as the basis of this review.

Alkylphosphocholines and curcumin induce programmed cell death in cutaneous T-cell lymphoma cell lines.

While most patients with early-stage cutaneous T-cell lymphomas (CTCL) have a very good prognosis, the survival of patients with extensive tumour stage and visceral involvement remains extremely poor and necessitates the development of more effective treatment modalities. In this study, we evaluated the in vitro effects of two alkylphosphocholines (APCs, miltefosine and erufosine) and the polyphenolic compound curcumin on 5 human CTCL cell lines (Hut-78, HH, MJ, My-La CD4+ and My-La CD8+). All tested drugs showed considerable cytotoxic activity, as determined by the MTT dye reduction assay.

Erufosine suppresses breast cancer in vitro and in vivo for its activity on PI3K, c-Raf and Akt proteins.

Purpose: This study investigated the antineoplastic effect of the membrane active alkylphosphocholine erufosine in breast carcinoma models in vitro and in vivo and determined its influence on the PI3K/Akt and Ras/Raf/MAPK signaling pathways.

Methods: The antiproliferative effect of erufosine in vitro was determined by the MTT dye reduction assay, and the antineoplastic efficacy on tumor growth was investigated by relating the mean total tumor volumes of treated and control rats. Immunoblot analysis was used for detecting changes in the expression level of the signal molecules p-PI3K (p-p85), p-Akt at Thr 308 and p-cRaf.

A particular expression pattern of CD13 epitope 7H5 in chronic lymphocytic leukaemia--a possible new therapeutic target.

A total of 50 patients with chronic lymphocytic leukaemia (CLL), as well as the B-cell leukaemia cell lines MEC-1, JVM-3, and BV-173 were studied in order to assess the incidence of CD13/aminopeptidase N (APN) immunolabelling with a monoclonal antibody 7H5 compared to LeuM7 and to CD13 mRNA levels, and to correlate these data with the cytotoxic and apoptosis-induction activity of the natural phenolic APN inhibitor curcumin. CD13/APN was detected in a significant proportion of B-CLL patients (42/50, 84%), immunolabelled by 7H5 (42/50) ± LeuM7 (10/50). Molecular analysis for CD13 transcripts confirmed these data, resulting in a specific RT-PCR product in CD13 positive cases.

Interleukin-6, osteopontin and Raf/MEK/ERK signaling modulate the sensitivity of human myeloma cells to alkylphosphocholines.

Alkylphosphocholines are highly active against multiple myeloma (MM) cells in vitro and are devoid of myelotoxicity. Little is known about the determinants of MM cell responsiveness or resistance to these drugs. In this study we investigated the effects of disease-relevant cytokines, such as interleukin-6 (IL-6) and osteopontin (OPN), on the in vitro antimyeloma activity of erufosine and perifosine.

An anti-apoptotic pattern correlates with multidrug resistance in acute myeloid leukemia patients: a comparative study of active caspase-3, cleaved PARPs, Bcl-2, Survivin and MDR1 gene.

Bone marrow samples of 17 acute myeloid leukemia (AML) patients were analyzed for apoptosis-related markers. The levels of active caspase-3 (aC-3), Bcl-2 and cleaved poly(ADP-ribose) polymerase (cPARP) were measured by flow cytometry and compared with survivin and MDR1 gene expression as defined by reverse transcriptase polymerase chain reaction (RT-PCR). The results showed heterogeneous patterns of intracellular levels of the studied proteins in AML patients: aC-3 (mean 34.

Erucylphospho-N,N,N-trimethylpropylammonium (erufosine) is a potential antimyeloma drug devoid of myelotoxicity.

Purpose: Erufosine is an i.v. injectable alkylphosphocholine which is active against various haematological malignancies in vitro.

In vitro biochemical and pharmacological evaluation of a novel cytotoxic dinuclear platinum(II) complex with 3-amino-5-methyl-5-phenylhydantoin.

An in vitro pharmacological evaluation of a novel dinuclear platinum complex ([KL(2)](2)[Pt(2)I(6)], where L is 3-amino-5-methyl-5-phenylhydantoin; Ad-1) was carried out. The cytotoxicity of [KL(2)](2)[Pt(2)I(6)] against human tumor cell lines was assessed using the MTT [-3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide] assay. The complex exerted concentration-dependent cytotoxic effects that were comparable or even superior to that of cisplatin.

Erucylphospho-N,N,N-trimethylpropylammonium shows substantial cytotoxicity in multiple myeloma cells.

Multiple myeloma (MM) is a frequent hematological malignancy that is incurable despite recent developments, such as proteasome and angiogenic inhibitors. Erucylphospho-N,N,N-trimethylpropylammonium (erufosine) is an i.v.

Novel N-(phosphonomethyl) glycine derivatives: Design, characterization and biological activity.

A series of Calpha,alpha-disubstituted cyclic derivatives of N-(phosphonomethyl) glycine have been synthesized and characterized. They exhibited moderate clastogenicity, low antiproliferative activity on mice bone marrow cells and well expressed cytotoxicity against human tumor cell lines. The 8- and 12-membered cyclic analogs proved superior to the remaining compounds and were found to trigger apoptotic cell death in DOHH-2 cells.

The expression level of the tumor suppressor retinoblastoma protein (Rb) influences the antileukemic efficacy of erucylphospho-N,N,N-trimethylpropylammonium (ErPC3).

The alkylphosphocholine erucylphospho-N,N,N-trimethylpropylammonium (ErPC3) is a promising new drug for treating various types of cancer. Its mechanism of action is not yet fully understood but is related to the Rb tumor suppressor protein. In the present study, we investigated the role of decreased Rb expression levels for the antileukemic efficacy of ErPC3 in BV-173 and K-562 CML-derived cell lines.

Antineoplastic and anticlastogenic properties of curcumin.

Curcumin is the pigment of turmeric and has been reported as a signal transduction modulator and inhibitor of transcription factors, for example, NF-kappaB. In our article we found a concentration-dependent cytotoxic activity of curcumin in a panel of eight leukemic cell lines (SKW-3, CEM, U-937, HL-60, HL-60/Dox, K-562, LAMA-84, and AR-230). Additive to synergistic interactions was recorded for combinations with bendamustine and idarubicine in SKW-3 and LAMA-84 cells.

Three-dimensional bioreactor cultures: a useful dynamic model for the study of cellular interactions.

The ex vivo expansion of hematopoietic cells is a developing area with emphasis on bioreactor systems for amelioration of culture conditions. A rational design of bioreactors, especially those allowing microgravity, could permit the production of stem cells and will offer new approaches for studying the mechanisms of proliferation, differentiation, and signal transduction of cultured cells. The efficacy of two commercially available bioreactors (rotating-vessel miniPERM and static INTEGRA CL 350) to support long-term bone marrow cell cultures (LTBMCC) and three-dimensional growth of Hodgkin's lymphoma HD-MY-Z cells was investigated.

Effects of the plant alkaloid thaliblastine on non-cross-resistant and sensitive human leukemia cells in relation with reversal of acquired anthracycline resistance.

Thaliblastine exhibits dose dependent cytotoxic effect on HL-60, HL-60/DOX, RHE and HD-MY-2 leukemia cells. Additionally, typical for apoptosis oligonucleosomal DNA fragmentation could be detected in leukemia cells treated with thaliblastine. Moreover, an MDR-phenotype reversing effect of thaliblastine was also identified.

Induction of apoptosis by erucylphospho-N,N,N-trimethylammonium is associated with changes in signal molecule expressionand location.

At concentrations effecting apoptosis, the alkylphosphocholine ErPC3 induced increased expression of the Rb protein in breast cancer (MCF-7) and leukemia (SKW-3, AR-230) cell lines as well as hypophosphorylation (K-562, CMLT-1, DOHH-2) and fragmentation of Rb (BV-173, SKW-3) in leukemia cell lines. ErPC3 exerts at least part of its antineoplastic activity by apoptosis, and this chain of events comprises early changes in the lipid raft fraction of the cellular membrane as well as modulation of different signal molecules, such as Abl, Bcr-Abl (fusion protein), and Rb.

Combination with an antisense oligonucleotide synergistically improves the antileukemic efficacy of erucylphospho-N,N,N-trimethylpropylammonium in chronic myeloid leukemia cell lines.

The aim of this study was to enhance the antileukemic efficacy of the alkylphosphocholine erucylphospho-N,N,N-trimethylpropylammonium (ErPC3) in chronic myeloid leukemia (CML)-derived cell lines by a bcr-directed antisense oligonucleotide (ASO-bcr). The mechanism was substantiated by Western blotting of the BCR-ABL expression level of CML cells, and the efficacy was substantiated by inhibition of colony formation compared with normal hematopoietic cells. The clonogenicity of K-562 cells expressing high levels of p210(BCR-ABL) was inhibited significantly by the ASO-bcr (T/C%, 30; P < 0.

Combination effects of alkylphosphocholines and gemcitabine in malignant and normal hematopoietic cells.

Cytosine arabinoside (ara-C) and 2',2'-difluorodeoxycytidine (Gem) were compared in leukemia cells, with Gem being more potent than ara-C. Gem was combined with hexadecylphosphocholine (HPC) or erucylphospho-N,N,N-trimethylpropanolamine (ErPC(3)) in resistant CML cells. Supra-additive effects were seen in K-562 cells after concomitant and sequential exposure of Gem followed by HPC.