Cytotoxic, Antiproliferative and Pro-Apoptotic Effects of 5-Hydroxyl-6,7,3',4',5'-Pentamethoxyflavone Isolated from Lantana ukambensis.

Lantana ukambensis (Vatke) Verdc. is an African food and medicinal plant. Its red fruits are eaten and highly appreciated by the rural population.

4-Hydroxybenzoic acid derivatives as HDAC6-specific inhibitors modulating microtubular structure and HSP90α chaperone activity against prostate cancer.

Histone deacetylase (HDAC)6 is a unique isoenzyme targeting specific substrates including α-tubulin and heat shock protein (HSP)90. HDAC6 is involved in protein trafficking and degradation, cell shape and migration. Deregulation of HDAC6 activity is associated with a variety of diseases including cancer leading to a growing interest for developing HDAC6 inhibitors.

A Survey of Marine Natural Compounds and Their Derivatives with Anti-cancer Activity Reported in 2012.

Although considerable effort and progress has been made in the search for new anticancer drugs and treatments in the last several decades, cancer remains a major public health problem and one of the major causes of death worldwide. Many sources, including plants, animals, and minerals, are of interest in cancer research because of the possibility of identifying novel molecular therapeutics. Moreover, structure-activity-relationship (SAR) investigations have become a common way to develop naturally derived or semi-synthetic molecular analogues with improved efficacy and decreased toxicity.

Hybrid curcumin compounds: a new strategy for cancer treatment.

Cancer is a multifactorial disease that requires treatments able to target multiple intracellular components and signaling pathways. The natural compound, curcumin, was already described as a promising anticancer agent due to its multipotent properties and huge amount of molecular targets in vitro. Its translation to the clinic is, however, limited by its reduced solubility and bioavailability in patients.

Eurycomanone and eurycomanol from Eurycoma longifolia Jack as regulators of signaling pathways involved in proliferation, cell death and inflammation.

Eurycomanone and eurycomanol are two quassinoids from the roots of Eurycoma longifolia Jack. The aim of this study was to assess the bioactivity of these compounds in Jurkat and K562 human leukemia cell models compared to peripheral blood mononuclear cells from healthy donors. Both eurycomanone and eurycomanol inhibited Jurkat and K562 cell viability and proliferation without affecting healthy cells.

Plumbagin modulates leukemia cell redox status.

Plumbagin is a plant naphtoquinone exerting anti-cancer properties including apoptotic cell death induction and generation of reactive oxygen species (ROS). The aim of this study was to elucidate parameters explaining the differential leukemia cell sensitivity towards this compound. Among several leukemia cell lines, U937 monocytic leukemia cells appeared more sensitive to plumbagin treatment in terms of cytotoxicity and level of apoptotic cell death compared to more resistant Raji Burkitt lymphoma cells.

From nature to bedside: pro-survival and cell death mechanisms as therapeutic targets in cancer treatment.

Cell death is an important physiological regulator during development, tissue homeostasis and stress response but it is also a protective tumor suppressive mechanism. Tumor cells almost universally acquire the ability to evade cell death pathways that in normal cells act as a protective mechanism to remove damaged cells. As a result, a population of death-resistant cells with accumulating genetic and epigenetic abnormalities contributes to malignant transformation.

Anticancer bioactivity of compounds from medicinal plants used in European medieval traditions.

Since centuries, natural compounds from plants, animals and microorganisms were used in medicinal traditions to treat various diseases without a solid scientific basis. Recent studies have shown that plants that were used or are still used in the medieval European medicine are able to provide relieve for many diseases including cancer. Here we summarize impact and effect of selected purified active natural compounds from plants used in European medieval medicinal traditions on cancer hallmarks and enabling characteristics identified by Hanahan and Weinberg.

Curcumin as a regulator of epigenetic events.

Epigenetic alterations correspond to changes in DNA methylation, covalent modifications of histones, or altered miRNA expression patterns. These three mechanisms are interconnected and appear to be key players in tumor progression and failure of conventional chemotherapy. Dietary components emerged as a promising source of new epigenetically active compounds able to reverse these alterations and to actively regulate gene expression as well as molecular targets implicated in tumorigenesis.

Anticancer effect of altersolanol A, a metabolite produced by the endophytic fungus Stemphylium globuliferum, mediated by its pro-apoptotic and anti-invasive potential via the inhibition of NF-κB activity.

Altersolanol A, a natural product from the endophytic fungus Stemphylium globuliferum isolated from the medicinal plant Mentha pulegium (Lamiaceae) growing in Morocco, shows cytotoxic, cytostatic, anti-inflammatory and anti-migrative activity against human chronic myeloid K562 leukemia and A549 lung cancer cells in a dose dependent manner without affecting the viability of non cancerous cells. Altersolanol A induces cell death by apoptosis through the cleavage of caspase-3 and -9 and through the decrease of anti-apoptotic protein expression. Moreover, we report here the importance of the distinct structural features of altersolanol A by testing other related anthracene derivatives in order to identify preliminary structure-activity relationships.

A survey of marine natural compounds and their derivatives with anti-cancer activity reported in 2011.

Cancer continues to be a major public health problem despite the efforts that have been made in the search for novel drugs and treatments. The current sources sought for the discovery of new molecules are plants, animals and minerals. During the past decade, the search for anticancer agents of marine origin to fight chemo-resistance has increased greatly.

Embellicines A and B: absolute configuration and NF-κB transcriptional inhibitory activity.

Two new metabolites, embellicines A and B (1 and 2), were isolated from the EtOAc extract of the fungus Embellisia eureka , an endophyte of the Moroccan plant Cladanthus arabicus (Asteraceae). The structures of these new compounds were determined on the basis of extensive one- and two-dimensional NMR spectroscopy as well as by high-resolution mass spectrometry. The absolute configuration of embellicine A (1) was determined by TDDFT ECD calculations of solution conformers, whereas that of embellicine B (2) was deduced based on ROESY correlations and on biogenetic considerations in comparison to 1.

Traditional West African pharmacopeia, plants and derived compounds for cancer therapy.

Traditional pharmacopeia is strongly involved in the continuous search for the well being of African populations. The World Health Organization (WHO) estimates that 80% of the population of developing countries relies on traditional medicine for their primary care needs. Medicinal plants are the major resource of this folk medicine where several species are used for the treatment of diseases with an inflammatory and/or infectious component as it is the case of old wounds, skin diseases and malfunctions affecting internal organs such as liver, lung, prostate and kidney.

Identification of differentially expressed proteins in curcumin-treated prostate cancer cell lines.

Due to high prevalence and slow progression of prostate cancer, primary prevention appears to be attractive strategy for its eradication. During the last decade, curcumin (diferuloylmethane), a natural compound from the root of turmeric (Curcuma longa), was described as a potent chemopreventive agent. Curcumin exhibits anti-inflammatory, anticarcinogenic, antiproliferative, antiangiogenic, and antioxidant properties in various cancer cell models.

Targeting the wingless signaling pathway with natural compounds as chemopreventive or chemotherapeutic agents.

The aberrant activation of the wingless (Wnt) signaling pathway is a key element involved in carcinogenesis as Wnt regulates a variety of cellular processes including proliferation, differentiation, survival, apoptosis and cell motility. Upon Wnt receptor activation, the canonical "Wnt/beta-catenin" as well as the non canonical "Wnt/planar cell polarity, Wnt/Ca²⁺" pathways are activated. This offers multiple possibilities to target the aberrant regulation of this signaling pathway in order to counteract cancer proliferation.

Anti-proliferative potential of curcumin in androgen-dependent prostate cancer cells occurs through modulation of the Wingless signaling pathway.

Activation of the Wingless (Wnt)/ß-catenin signaling pathway contributes to prostate tumorigenesis and metastasis. Depending of the stage of prostate cancer development, current drug therapies are of limited efficiency, so that prevention with natural compounds appears as an attractive strategy especially due to the slow progressive development of prostate cancer. We report here that the chemopreventive agent curcumin from the rhizome of Curcuma longa was able to affect cell proliferation of androgen-dependent prostate cancer through the induction of cell cycle arrest in G2 and modulation of Wnt signaling.

UNBS1450, a steroid cardiac glycoside inducing apoptotic cell death in human leukemia cells.

Cardiac steroids are used to treat various diseases including congestive heart failure and cancer. The aim of this study was to investigate the anti-leukemic activity of UNBS1450, a hemi-synthetic cardenolide belonging to the cardiac steroid glycoside family. Here, we report that, at low nanomolar concentrations, UNBS1450 induces apoptotic cell death.

Curcumin-the paradigm of a multi-target natural compound with applications in cancer prevention and treatment.

As cancer is a multifactor disease, it may require treatment with compounds able to target multiple intracellular components. We summarize here how curcumin is able to modulate many components of intracellular signaling pathways implicated in inflammation, cell proliferation and invasion and to induce genetic modulations eventually leading to tumor cell death. Clinical applications of this natural compound were initially limited by its low solubility and bioavailability in both plasma and tissues but combination with adjuvant and delivery vehicles was reported to largely improve bio-availability of curcumin.

Chemopreventive potential of curcumin in prostate cancer.

The long latency and high incidence of prostate carcinogenesis provides the opportunity to intervene with chemoprevention in order to prevent or eradicate prostate malignancies. We present here an overview of the chemopreventive potential of curcumin (diferuloylmethane), a well-known natural compound that exhibits therapeutic promise for prostate cancer. In fact, it interferes with prostate cancer proliferation and metastasis development through the down-regulation of androgen receptor and epidermal growth factor receptor, but also through the induction of cell cycle arrest.

Effect of curcumin on nuclear factor kappaB signaling pathways in human chronic myelogenous K562 leukemia cells.

Curcumin, a natural product isolated from the plant Curcuma longa, has a diverse range of molecular targets that influence numerous biochemical and molecular cascades. Curcumin has been shown to inhibit nuclear factor kappaB (NF-kappaB) activation at several steps in the NF-kappaB signaling pathways and thereby controls numerous NF-kappaB-regulated genes involved in various diseases. In the present study, we investigated the effect of curcumin pretreatment on 84 tumor necrosis factor-alpha (TNF-alpha)-activated genes of NF-kappaB pathways in K562 cells, using a real-time PCR array.

Gene expression profiling related to anti-inflammatory properties of curcumin in K562 leukemia cells.

A strong relationship exists between inflammation and carcinogenesis. To bring insights into the anti-inflammatory mechanisms by which chemopreventive agents, such as curcumin, are able to counteract the action of inflammation mediators, such as tumor necrosis factor-alpha (TNF-alpha), we compared gene expression profiles in K562 cells treated with curcumin-TNF-alpha versus TNF-alpha alone. Microarray data analysis revealed that, among the 376 differentially expressed genes by curcumin treatment, genes belonging to the cell cycle and the Janus kinase-signal transducer and activator of transcription signaling pathways were downregulated.

Induction of heat shock response by curcumin in human leukemia cells.

Heat shock response is an adaptive response, which helps the cells to regulate their physiological homeostasis under stress. Here we show that the natural compound curcumin induces nuclear translocation of the heat shock transcription factor (HSF)-1, its binding to a heat shock regulatory element (HSE), and the subsequent activation of the hsp70 promoter through the extracellular regulated kinase (ERK)/mitogen activated protein (MAP) ERK (MEK) and c-jun N-terminal kinase (JNK) pathways, but not through p38. We observe that curcumin activates hsp70A and hsp70B mRNA transcription, increases HSP protein expression but decreases the expression of Bag-1, a Hsp70 co-chaperone in K562 cells.

Tumor necrosis factor alpha induces gamma-glutamyltransferase expression via nuclear factor-kappaB in cooperation with Sp1.

Gamma-glutamyltransferase (GGT) cleaves the gamma-glutamyl moiety of glutathione (GSH), an endogenous antioxidant, and is involved in mercapturic acid metabolism and in cancer drug resistance when overexpressed. Moreover, GGT converts leukotriene (LT) C4 into LTD4 implicated in various inflammatory pathologies. So far the effect of inflammatory stimuli on regulation of GGT expression and activity remained to be addressed.

Primary photodamage sites and mitochondrial events after Foscan photosensitization of MCF-7 human breast cancer cells.

To determine the initial photodamage sites of Foscan-mediated photodynamic treatment, we evaluated the enzymatic activities in selected organelles immediately after light exposure of MCF-7 cells. The measurements indicated that the enzymes located in the Golgi apparatus (uridine 5'-diphosphate galactosyl transferase) and in the endoplasmic reticulum (ER) (nicotinamide adenine dinucleotide [reduced] [NADH] cytochrome c [cyt c] reductase) are inactivated by the treatment, whereas mitochondrial marker enzymes (cyt c oxidase and dehydrogenases) were unaffected. This indicates that the ER and the Golgi apparatus are the primary intracellular sites damaged by Foscan-mediated PDT in MCF-7 cells.

The multidrug resistance modulator SDZ-PSC 833 potentiates the photodynamic activity of chlorin e6 independently of P-glycoprotein in multidrug resistant human breast adenocarcinoma cells.

Photodynamic therapy has clinical indications in treatment of localized cancers and could be interesting for eradication of local recurrence of chemoresistant tumors. In the present study, the intracellular accumulation and distribution of chlorin e6 was investigated in MCF-7 and in P-glycoprotein overexpressing, doxorubicin resistant MCF-7/DXR cell lines. After 3-h incubation with chlorin e6 (1.