The Multifaceted Roles of NRF2 in Cancer: Friend or Foe?

Physiological concentrations of reactive oxygen species (ROS) play vital roles in various normal cellular processes, whereas excessive ROS generation is central to disease pathogenesis. The nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor that regulates the cellular antioxidant systems in response to oxidative stress by governing the expression of genes encoding antioxidant enzymes that shield cells from diverse oxidative alterations. NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) have been the focus of numerous investigations in elucidating whether NRF2 suppresses tumor promotion or conversely exerts pro-oncogenic effects. NRF2 has been found to participate in various pathological processes, including dysregulated cell proliferation, metabolic remodeling, and resistance to apoptosis. Herein, this review article will examine the intriguing role of phase separation in activating the NRF2 transcriptional activity and explore the NRF2 dual impacts on tumor immunology, cancer stem cells, metastasis, and long non-coding RNAs (LncRNAs). Taken together, this review aims to discuss the NRF2 multifaceted roles in both cancer prevention and promotion while also addressing the advantages, disadvantages, and limitations associated with modulating NRF2 therapeutically in cancer treatment.

Discovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival.

A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such activities were discussed in terms of molecular descriptors such as half-wave potentials, hydrophobicity and molar refractivity. Compounds 4 and 11 displayed the highest antiproliferative activity against the three cancer cells and were therefore further investigated. The in silico prediction of drug likeness, using pkCSM and SwissADME explorer online, shows that compound 11 is a suitable lead molecule to be developed. Moreover, the expressions of key genes were studied in DU-145 cancer cells. They include genes involved in apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle regulation (CDC25A), cell cycle progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) and inflammatory pathways (TNF). Compound 11 displays an interesting profile because among these genes, mTOR was significantly less expressed as compared to control conditions. Molecular docking shows that compound 11 has good affinity with mTOR, unraveling a potential inhibitory effect on this protein. Due to the key role of mTOR on tumor metabolism, we suggest that impaired DU-145 cells proliferation by compound 11 is caused by a reduced mTOR expression (less mTOR protein) and inhibitory activity on mTOR protein.

Vitamin C (Ascorbate) and Redox Topics in Cancer.

Significance: Vitamin C (ascorbate), in regard to its effectiveness against malignancies, has had a controversial history in cancer treatment. It has been shown that in vitro and in vivo anticancer efficacy of ascorbate relies on its pro-oxidant effect mainly from an increased generation of reactive oxygen species (ROS). A growing understanding of its anticancer activities and pharmacokinetic properties has prompted scientists to re-evaluate the significance of ascorbate in cancer treatment. Recent Advances: A recent resurge in ascorbate research emerged after discovering that, at high doses, ascorbate preferentially kills Kirsten-Ras (K-ras)- and B-raf oncogene (BRAF)-mutant cancer cells. In addition, some of the main hallmarks of cancer cells, such as redox homeostasis and oxygen-sensing regulation (through inhibition of hypoxia-inducible factor-1 alpha [HIF-1α] activity), are affected by vitamin C. Critical Issues: Currently, there is no clear consensus from the literature in regard to the beneficial effects of antioxidants. Results from both human and animal studies provide no clear evidence about the benefit of antioxidant treatment in preventing or suppressing cancer development. Since pro-oxidants may affect both normal and tumor cells, the extremely low toxicity of ascorbate represents a main advantage. This guarantees the safe inclusion of ascorbate in clinical protocols to treat cancer patients. Future Directions: Current research could focus on elucidating the wide array of reactions between ascorbate and reactive species, namely ROS, reactive nitrogen species as well as reactive sulfide species, and their intracellular molecular targets. Unraveling these mechanisms could allow researchers to assess what could be the optimal combination of ascorbate with standard treatments.

New 2-Acetyl-3-aminophenyl-1,4-naphthoquinones: Synthesis and In Vitro Antiproliferative Activities on Breast and Prostate Human Cancer Cells.

The reaction of 2-acyl-1,4-naphthoquinones with N,N-dimethylaniline and 2,5-dimethoxyaniline, promoted by catalytic amounts of CeCl3·7H2O under "open-flask" conditions, produced a variety of 2-acyl-3-aminophenyl-1,4-naphthoquinones structurally related to the cytotoxic 2-acetyl-3-phenyl-1,4-naphthoquinone, an inhibitor of the heat shock chaperone protein Hsp90. The members of the 2-acyl-3-aminophenyl-1,4-naphthoquinone series were isolated in good yields (63-98%). The cyclic voltammograms of the 2-acyl-3-aminophenyl-1,4-naphthoquinone exhibit two one-electron reduction waves to the corresponding radical-anion and dianion and two quasireversible oxidation peaks. The first and second half-wave potential values (E 1/2) of the members of the series are sensitive to the push-pull electronic effects of the substituents in the naphthoquinone scaffold. Furthermore, the in vitro antiproliferative properties of these new quinones were evaluated on two human cancer cells DU-145 (prostate) and MCF-7 (mammary) and a nontumorigenic HEK-293 (kidney) cell line, using the MTT colorimetric method. Two members, within the series, exhibited interesting cytotoxic activities on human prostate and mammary cancer cells.

In Vitro Inhibition of Hsp90 Protein by Benzothiazoloquinazolinequinones Is Enhanced in The Presence of Ascorbate. A Preliminary In Vivo Antiproliferative Study.

A series of benzo[g]benzothiazolo[2,3-b]quinazoline-7,12-quinones were prepared from 2-acylnaphthohydroquinones and 2-aminobenzothiazoles and were evaluated for their in vitro antiproliferative activity. After screening using the MTT reduction assay, their IC50 values were calculated on a panel of cancer cells (T24, DU-145, MCF-7). Current standard anticancer drugs were included as control, and their calculated IC50 values were 7.8 and 23.5 µM for 5-fluorouracil and tamoxifen, respectively. Non-cancer cells (AG1523) were included to assess cancer cell sensitivity and drug selectivity. Four members of the series, with IC50 values from 0.11 to 2.98 µM, were chosen for further assays. The selected quinones were evaluated regarding their effects on cancer cell proliferation (clonogenic assay) and on Hsp90 and poly(ADPribose)polymerase (PARP) protein integrity. The most active compound (i.e., 15) substantially inhibited colony forming unit (CFU) formation at 0.25 µM. In the presence of ascorbate, it induced an oxidative cleavage of Hsp90 but had no effect on PARP protein integrity. In an in vivo animal model, it discreetly increased the mean survival time (m.s.t.) of tumor-bearing mice. In light of these results, compound 15 represents a potential lead-molecule to be further developed.

Cancer Cell Sensitivity to Redox-Cycling Quinones is Influenced by NAD(P)H: Quinone Oxidoreductase 1 Polymorphism.

BACKGROUND: Cancer cell sensitivity to drugs may be associated with disturbed antioxidant enzymes expression. We investigated mechanisms of resistance by using oxidative stress-resistant MCF-7 breast cancer cells (Resox cells). Since nicotinamide adenine dinucleotide phosphate (NAD(P)H): quinone oxidoreductase-1 (NQO1) is modified in tumors and oxidative stress-resistant cells, we studied its role in cells exposed to ß-lapachone, menadione, and doxorubicin. METHODS: Normal mammary epithelial 250MK, MCF-7, and Resox cells were employed. NQO1 expression and enzyme activity were determined by quantitative polymerase chain reaction (RT-PCR), immunoblotting, and biochemical assays. Dicoumarol and gene silencing (siRNA) were used to modulate NQO1 expression and to assess its potential drug-detoxifying role. MTT (3-(4,5-dimethylthia-zolyl-2)-2,5-diphenyltetrazolium bromide) or clonogenic assays were used to investigate cytotoxicity. NQO1 variants, NQO1*1 (wt), and NQO1*2 (C609T), were obtained by transfecting NQO1-null MDA-MB-231 cell line. RESULTS: Resox cells have higher NQO1 expression than MCF-7 cells. In 250MK cells its expression was low but enzyme activity was higher suggesting a variant NQO1 form in MCF-7 cells. MCF-7 and Resox cells are heterozygous NQO1*1 (wt)/ NQO1*2 (C609T). Both NQO1 polymorphism and NQO1 overexpression are main determinants for cell resistance during oxidative stress. NQO1 overexpression increases cell sensitivity to ß-lapachone whereas NQO1*2 polymorphism triggers quinone-based chemotherapies-sensitivity. CONCLUSIONS: NQO1 influences cancer cells redox metabolism and their sensitivity to drugs. We suggest that determining NQO1 polymorphism may be important when considering the use of quinone-based chemotherapeutic drugs.

Half-Wave Potentials and In Vitro Cytotoxic Evaluation of 3-Acylated 2,5-Bis(phenylamino)-1,4-benzoquinones on Cancer Cells.

A broad range of 3-acyl-2,5-bis(phenylamino)-1,4-benzoquinones were synthesized and their voltammetric values, as well as in vitro cancer cell cytotoxicities, were assessed. The members of this series were prepared from acylbenzoquinones and phenylamines, in moderate to good yields (47-74%), through a procedure involving a sequence of two in situ regioselective oxidative amination reactions. The cyclic voltammograms of the aminoquinones exhibit two one-electron reduction waves to the corresponding radical-anion and dianion, and two quasi-reversible oxidation peaks. The first and second half-wave potential values (E1/2) of the members of the series were sensitive to the push-pull electronic effects of the substituents around the benzoquinone nucleus. The in vitro cytotoxic activities of the 3-acyl-2,5-bis(phenylamino)-1,4-benzoquinones against human cancer cells (bladder and prostate) and non-tumor human embryonic kidney cells were measured using the MTT colorimetric method. The substitution of both aniline groups, by either methoxy (electron donating effect) or fluorine (electron withdrawal effect), decreased the cytotoxicity in the aminoquinones. Among the members of the unsubstituted phenylamino series, two of the 18 compounds showed interesting anti-cancer activities. A preliminary assay, looking for changes in the expression of selected genes, was performed. In this context, the two compounds increased TNF gene expression, suggesting an association with an inflammatory-like response.

Targeting hsp90 family members: A strategy to improve cancer cell death.

A crucial process in biology is the conversion of the genetic information into functional proteins that carry out the genetic program. However, a supplementary step is required to obtain functional proteins: the folding of the newly translated polypeptides into well-defined, three-dimensional conformations. Proteins chaperones are crucial for this final step in the readout of genetic information, which results in the formation of functional proteins. In this review, a special attention will be given to the strategies targeting hsp90 family members in order to increase cancer cell death. We argue that disruption of hsp90 machinery and the further client protein degradation is the main consequence of hsp90 oxidative cleavage taking place at the N-terminal nucleotide-binding site. Moreover, modulation of Grp94 expression will be discussed as a potential therapeutic goal looking for a decrease in cancer relapses.

Chemical composition, in vitro cytotoxic and antioxidant activities of the essential oil of Peruvian Minthostachys mollis Griseb / Composición química, actividades citotóxicas y antioxidantes in vitro del aceite esencial de Minthostachys mollis Griseb peruano

The composition of the essential oil obtained by hydrodistillation from Minthostachys mollis Griseb (Lamiaceae) aerial parts was determined by GC and GC/MS. Menthone (13.2%), pulegone (12.4%), cis-dihydrocarvone (9.8%) and carvacrol acetate (8.8%) were the main essential oil components. The cytotoxic activity of the essential oil was in vitro measured using the MTT colorimetric assay. IC50 values were calculated on healthy non-tumor cells (HEK-293) and three human cancer cell lines (T24, DU-145 and MCF-7). In such latter cells, the estimated values were around 0.2 mg/mL. In addition, the antioxidant activity was determined by interaction with the stable free radical 2,2"-diphenyl-1-picrylhydrazyl. The essential oil was almost devoid of antioxidant activity indicating that its anti-proliferative action relies on other unknown mechanism.

La composición del aceite esencial obtenido por hidrodestilación a partir de partes aéreas de Minthostachys mollis Griseb (Lamiaceae) se determinó mediante GC y GC/MS. Mentona (13.2%), pulegona (12.4%), junto con cis-dihidrocarvona (9.8%) y acetato de carvacrol (8.8%) fueron los principales componentes del aceite esencial. La actividad citotóxica del aceite esencial se midió in vitro utilizando el ensayo colorimétrico MTT tanto en células sanas no tumorales (HEK-293) como en tres líneas celulares de cáncer humano (T24, DU-145 y MCF-7). Los valores de IC50 calculados fueron de alrededor de 0.2 mg/mL. Además, se determinó la actividad antioxidante por su interacción con el radical libre 2,2"-difenil-1-picrilhidrazilo. El aceite esencial tiene baja actividad antioxidante, lo que indica que su acción antiproliferativa depende de otro mecanismo desconocido.

Glucose-regulated protein of 94 kDa contributes to the development of an aggressive phenotype in breast cancer cells.

Grp94 plays an essential role in protein assembly. We previously suggested that Grp94 overexpression is involved in tumor aggressiveness. However, the underlying mechanisms remain unknown. Since many tumors display high Grp94 levels, we investigated the effects of tumor microenvironment on the regulation of this chaperone expression. First, we found out that hypoxia did not change Grp94 expression in the human tumor cell lines MCF-7 (breast cancer) and HepG2 (liver cancer). Second, glucose deprivation significantly increased Grp94 protein levels. Subsequently, we focused in the putative role of Grp94 in the acquisition of an aggressive phenotype by cancer cells. Using a more aggressive cancer cell model (MDA-MB-231 breast tumor cells), we found out that Grp94 knockdown using siRNA decreased the invasive capacity of cancer cells. Moreover, cells with decreased Grp94 levels displayed an enhanced sensitivity of tumor cells to doxorubicin, a standard drug in the treatment of breast cancer. Taken together, our results suggest that the expression of Grp94 is linked to tumor aggressiveness. Therefore, targeting Grp94 could be an effective way to inhibit tumor growth improving chemotherapy outcome.

Targeting Akt as strategy to kill cancer cells using 3-substituted 5-anilinobenzo[c]isoxazolequinones: A preliminary study.

Several new 3-substituted 5-anilinobenzo[c]isoxazolequinones were synthesized from 1,4-benzoquinone and alkyl- or arylcarbaldehydes by a three-step synthetic sequence. The new compounds (3a-h) were tested in vitro in normal human fibroblasts and two cancer cell lines for their cytotoxic activity. The range of IC50 values obtained for the compounds was from 3.4 to 74.2µM. Five members of the series (3b, 3d, 3e, 3f, 3g) were further selected and evaluated as inhibitors of the Hsp90 chaperoning function taking Akt as example of Hsp90 client proteins. We also evaluated the changes of intracellular levels of GSH and ATP as markers of cellular metabolic status in response to these compounds in T24 cells. One of such isoxazolquinones (3b) decreased the expression of Akt, PARP and Hsp90. Compounds 3b and 3d decreased the amount of ATP but caused no effect on GSH levels. These compounds also activated caspase-3 but an apoptosis-like type of cell death was unlike since PARP protein was not cleaved and caspase activation was substantially lower than its activation induced by staurosporine, a known caspase-3 activator in T24 cells. Taken together, preliminary results led to the discovery of an original lead compound (3b) which can be used as model to obtain new Akt inhibitors.

Use of a cocktail of spin traps for fingerprinting large range of free radicals in biological systems.

It is well established that the formation of radical species centered on various atoms is involved in the mechanism leading to the development of several diseases or to the appearance of deleterious effects of toxic molecules. The detection of free radical is possible using Electron Paramagnetic Resonance (EPR) spectroscopy and the spin trapping technique. The classical EPR spin-trapping technique can be considered as a "hypothesis-driven" approach because it requires an a priori assumption regarding the nature of the free radical in order to select the most appropriate spin-trap. We here describe a "data-driven" approach using EPR and a cocktail of spin-traps. The rationale for using this cocktail was that it would cover a wide range of biologically relevant free radicals and have a large range of hydrophilicity and lipophilicity in order to trap free radicals produced in different cellular compartments. As a proof-of-concept, we validated the ability of the system to measure a large variety of free radicals (O-, N-, C-, or S- centered) in well characterized conditions, and we illustrated the ability of the technique to unambiguously detect free radical production in cells exposed to chemicals known to be radical-mediated toxic agents.

Chemical composition and antimicrobial activity of essential oil of peruvian dalea strobilacea barneby / Composición química y actividad antimicrobiana del aceite esencialde la planta peruana dalea strobilaceae barneby

The composition of the essential oil obtained by hydrodistillation from Dalea strobilacea Barneby (Fabaceae) aerial parts was examined by GC and GC/MS. beta-Phellandrene (44 percent) together with alpha-pinene (18 percent) were the main essential oil components. Antimicrobial activity of the essential oil was evaluated against eight bacterial strains. A moderate growth inhibition of Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis was shown by the essential oil.

La composición del aceite esencial de Dalea strobilacea Barneby (Fabaceae) obtenido por hidrodestilación de las partes aereas fue examinada por CG y CG/EM. beta-felandreno (44 por ciento) junto con alfa-pineno (18 por ciento) fueron los principales componentes del aceite esencial. La actividad antimicrobiana del aceite esencial fue evaluada contra ocho cepas bacterianas. El aceite esencial inhibió moderadamente el crecimiento de Klebsiella pneumoniae, Staphylococcus aureus y Enterococcus faecalis.

Silibinin Inhibits Proliferation and Migration of Human Hepatic Stellate LX-2 Cells.

BACKGROUND: Proliferation of hepatic stellate cells (HSCs) play pivotal role in the progression of hepatic fibrosis consequent to chronic liver injury. Silibinin (SBN), a flavonoid compound, has shown to possess cell cycle arresting potential against many actively proliferating cancers cell lines. The objective of this study was to evaluate the anti-proliferative and cell cycle arresting properties of SBN in rapidly proliferating human hepatic stellate LX-2 cell line. METHODS: LX-2 cells were fed with culture medium supplemented with different concentrations of SBN (10, 50 and 100 µM). After 24 and 96 h of treatment, total cell number was determined by counting. Cytotoxicity was evaluated by trypan blue dye exclusion test. The expression profile of cMyc and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expressions was evaluated by Western blotting. Oxidative stress marker genes profile was quantified using qPCR. The migratory response of HSCs was observed by scrape wound healing assay. RESULTS: SBN treatments significantly inhibit the LX-2 cell proliferation (without affecting its viability) in dose dependent manner. This treatment also retards the migration of LX-2 cells toward injured area. In Western blotting studies SBN treatment up regulated the protein expressions of PPAR-γ and inhibited cMyc. CONCLUSION: The present study shows that SBN retards the proliferation, activation and migration of LX-2 cells without inducing cytotoxicity and oxidative stress. The profound effects could be due to cell cycle arresting potential of SBN.

Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone-Amino Acid Derivatives.

A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure-activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC50 ranging from 0.5 to 6.25 µM and also by their good selectivity indexes (≥2.24).

Modulatory Effect of 2-(4-Hydroxyphenyl)amino-1,4-naphthoquinone on Endothelial Vasodilation in Rat Aorta.

The vascular endothelium plays an essential role in the control of the blood flow. Pharmacological agents like quinone (menadione) at various doses modulate this process in a variety of ways. In this study, Q7, a 2-phenylamino-1,4-naphthoquinone derivative, significantly increased oxidative stress and induced vascular dysfunction at concentrations that were not cytotoxic to endothelial or vascular smooth muscle cells. Q7 reduced nitric oxide (NO) levels and endothelial vasodilation to acetylcholine in rat aorta. It also blunted the calcium release from intracellular stores by increasing the phenylephrine-induced vasoconstriction when CaCl2 was added to a calcium-free medium but did not affect the influx of calcium from extracellular space. Q7 increased the vasoconstriction to BaCl2 (10-3 M), an inward rectifying K+ channels blocker, and blocked the vasodilation to KCl (10-2 M) in aortic rings precontracted with BaCl2. This was recovered with sodium nitroprusside (10-8 M), a NO donor. In conclusion, Q7 induced vasoconstriction was through a modulation of cellular mechanisms involving calcium fluxes through K+ channels, and oxidative stress induced endothelium damage. These findings contribute to the characterization of new quinone derivatives with low cytotoxicity able to pharmacologically modulate vasodilation.

Determination of sun protection factor and antioxidant properties of six Chilean Altiplano plants / Determinación del factor de protección solar y propiedades antioxidante de seis plantas del Altiplano Chileno

In the present study, we investigated sun protection factor and antioxidant properties of Parastrephia lepidophyla Cabr., Fabiana squamata Phil., Ephedra chilensis K.Presl., Lampaya medicinalis Phil., Baccharis tola Phil., and Azorella compacta Phil. The ethanol extracts were tested regarding their in vitro free radical scavenger ability and sun protection factor (SPF). Due to its antioxidant and photoprotective properties, B. tola is a promising candidate for use in cosmetic formulations. To evaluate the regenerative capacity of the B. tola extract, the planarian regeneration assay (Dugesia tigrina) was performed. Identification of phenolic compounds in B. tola, was performed by HPLC-ESI-MS/MS. Based on freeze-dried extracts of B. tola, a facial cream and a biphasic lotion with repairing tip action were formulated. These two formulations were evaluated by additional assays including organoleptic tests, measurement of pH, centrifugation and patch test to check a potential hypersensitivity (skin irritation) which can be induced by the products as well as a sensory survey. Stability studies, carried out over 12 months, prove that formulations were stable over time. It can be concluded that both products are innovative and shown solar protection, antioxidant and regenerative properties.

En el presente estudio, hemos investigado el factor de protección solar y propiedades antioxidantes de Parastrephia lepidophyla Cabr., Fabiana squamata Phil., Ephedra chilensis K.Presl., Lampaya medicinalis Phil., Baccharis tola Phil., y Azorella compacta Phil. Los extractos etanolicos fueron sometidos a ensayos como: evaluación in vitro de la actividad atrapadora de radicales libres y factor de protección solar (FPS). Debido a las propiedades antioxidantes y fotoprotectoras, B. tola es un candidato ideal para ser usado en formulaciones cosméticas. Se evaluó la capacidad regenerativa de B. tola en ensayos de planaria (Dugesia tigrina). Se identificó polifenoles por HPLC-ESI-MS/MS en B. tola. Se formularon una crema facial y una loción bifásica reparadora de puntas del cabello, en base a extractos liofilizados de Ñaca, a los cuales se le realizaron controles organolépticos, evaluación de pH, centrifugación, test de parche para evaluar la posible reacción de sensibilidad que pueden ocasionar los productos, comprobando que estos no producen irritación dérmica y posterior encuesta sensorial. Posteriormente, se realizaron estudios de estabilidad a lo largo de 12 meses, demostrando ser estable en el tiempo. Se puede concluir que ambos productos son innovadores y que muestran factor de protección solar, propiedades antioxidantes y regeneradoras.

Acantholippia deserticola essential oil as a natural pesticide againstagricultural plagues woolly whitefly [Aleurothrixus floccosus (Maskell)],Chilean false red mite (Brevipalpus chilensis Baker) and two-spotted mite(Tetranychus urticae Koch) / Aceite esencial de Acantholippia deserticola como pesticida natural contra plagas agrícolas como mosquita blanca algodonosa [Aleurothrixus floccosus (Maskell)], falsa arañita de la vid (Brevipalpus chilensis Baker) y arañita bimaculada (Tetranychus urticae Koch)

Different concentrations of essential oil obtained from Acantholippia deserticola (Phil.ex F. Phil.) Moldenke were assessed against Chilean agricultural pests like Aleurothrixus floccosus (Maskell), Brevipalpus chilensis Baker, and Tetranychus urticae Koch. Thebioassays were carried out under laboratory conditions and both direct and residual applications were done through Potter precision spraytower test. The oil was obtained by steam distillation containing a rich fraction of alpha and beta-thujones (88.4 percent) and it shows marked toxic effects against pests. Indeed, a mortality of 82 percent and 89 percent was observed in both B. chilensis and T. urticae after 48 h whereas in A. floccosus over 97 percent of mortality was seen after 7 days. These results open the possibility to use essential oil from Acantholippia deserticola as natural pesticide.

Se evaluó el efecto a diferentes concentraciones de una solución de aceite esencial de Acantholippia deserticola sobre plagas agrícolas en Chile, tales como Aleurothrixus floccosus (Maskell), Brevipalpus chilensis Baker y Tetranychus urticae Koch. Los bioensayos fueron realizados mediante una torre de Potter en condiciones de laboratorio y las aplicaciones fueron directas y residuales. El aceite se obtuvo por hidrodestilación, el cual contenía una gran cantidad de alfa and beta-tuyonas (88.4 por ciento), mostrando marcados efectos tóxicos para A. floccosus, con un 97 por ciento de mortalidad después de 7 d y, para B. chilensis, y T. urticae, con una mortalidad de 82 por ciento y 89 por ciento respectivamente, después de 48 h. Estos resultados abren la posibilidad de usar aceite esencial de Acantholippia deserticola como pesticida natural.

Antidepressant and anxiolytic-like effects of essential oil from Acantholippia deserticola Phil in female rats / Efecto ansiolítico y antidepresivo del aceite esencial de Acantholippia deserticola Phil en ratas hembras

Acantholippia deserticola (Phil.ex F. Phil.) Moldenke is a Verbenaceae that has long been used in traditional medicine in Tarapacá (Chile) as an analgesic, anti-inflammatory and aphrodisiac agent. Sincé alpha - and beta -thujone were identified as the main constituents (88.4 percent) of the essential oil from this plant, we investigated its biological properties. The results show that the essential oil from Acantholippia deserticola decreased locomotive and rearing activity compared to control group rats, including those treated with diazepam, but the essential oil had no effects on head movements or grooming. The essential oil also had significant anxiolytic and antidepressant effects. This essential oil, therefore, has sedative, anxiolytic and antidepressant actions on the rat central nervous system.

Acantholippia deserticola es una Verbenaceae de uso en la medicina tradicional como analgésico, antiinflamatorio y afrodisíaco en la región de Tarapacá, Chile. En el aceite esencial se ha identificado alfa - and beta -tuyonas como principales constituyentes (88.4 por ciento) de esta planta, que ha llevado a investigar sus propiedades biológicas. Los resultados muestran que el aceite esencial de Acantholippia deserticola disminuye la locomoción y el levantamiento en dos patas, en comparación con el grupo control, incluido el tratado por el diazepam, pero el aceite esencial no tuvo efecto sobre la sacudida de cabeza y el acicalamiento. En ambas pruebas, se observa un efecto significativo del aceite esencial en los efectos ansiolíticos y antidepresivos, lo que indica que el aceite esencial tiene actividad sedante, ansiolítica y antidepresiva en el sistema nervioso central.

Biological evaluation of 3-acyl-2-arylamino-1,4-naphthoquinones as inhibitors of Hsp90 chaperoning function.

Hsp90 is a chaperone that plays a key function in cancer cells by stabilizing proteins responsible of cell growth and survival. Disruption of the Hsp90 chaperone machinery leads to the proteasomal degradation of its client proteins. Hsp90 appears then as an attractive target for the development of new anticancer molecules. We have shown that ascorbate- driven menadione-redox cycling inhibits Hsp90 activity by provoking an N-terminal cleavage of the protein, inducing the degradation of several of its client proteins. Since the mechanism involves an oxidative stress, we explored the effect of a series of diverse donor-acceptor 3-acyl-2-phenylamino 1,4-naphthoquinones on Hsp90 integrity, in the presence of ascorbate. Results show that quinone-derivatives that bear two electroactive groups (namely quinone and nitro) exhibit the highest inhibitory activity (Hsp90 cleavage and cell death). The biological activity of the series mainly relies on their redox capacity and their lipophilicity, which both modulate the ability of these compounds to induce a cytotoxic effect in K562 cells. As observed with other redox cycling quinones, the protein cleavage is blocked in the presence of N-terminal Hsp90 inhibitors suggesting that the availability or occupancy of nucleotide binding site in the N-terminal pocket of Hsp90 plays a critical role. In addition the survival of cancer cells and their metabolic and redox homeostasis were strongly impaired by the presence of ascorbate. Since these effects were similar to that obtained by ascorbate/menadione and they were blocked by the antioxidant N-acetylcyteine (NAC), it appears that oxidative stress is a major component of this cytotoxicity.