Inclusion Complexes of Litsea cubeba (Lour.) Pers Essential Oil into ß-Cyclodextrin: Preparation, Physicochemical Characterization, Cytotoxicity and Antifungal Activity.

The uses of natural compounds, such as essential oils (EOs), are limited due to their instability to light, oxygen and temperature, factors that affect their application. Therefore, improving stability becomes necessary. The objective of this study was to prepare inclusion complexes of Litsea cubeba essential oil (LCEO) with ß-cyclodextrin (ß-CD) using physical mixing (PM), kneading (KN) and co-precipitation (CP) methods and to evaluate the efficiency of the complexes and their physicochemical properties using ATR-FTIR, FT-Raman, DSC and TG. The study also assessed cytotoxicity against human colorectal and cervical cancer cells and antifungal activity against Aspergillus flavus and Fusarium verticillioides. The complexation efficiency results presented significant evidence of LCEO:ß-CD inclusion complex formation, with KN (83%) and CP (73%) being the best methods used in this study. All tested LCEO:ß-CD inclusion complexes exhibited toxicity to HT-29 cells. Although the cytotoxic effect was less pronounced in HeLa tumor cells, LCEO-KN was more active against Hela than non-tumor cells. LCEO-KN and LCEO-CP inclusion complexes were efficient against both toxigenic fungi, A. flavus and F. verticillioides. Therefore, the molecular inclusion of LCEO into ß-CD was successful, as well as the preliminary biological results, evidencing that the ß-CD inclusion process may be a viable alternative to facilitate and increase future applications of this EO as therapeutic medication, food additive and natural antifungal agent.

Article review: Brazilin as potential anticancer agent.

Brazilin is the main compound in Caesalpinia sappan and Haematoxylum braziletto, which is identified as a homoisoflavonoid based on its molecular structure. These plants are traditionally used as an anti-inflammatory to treat fever, hemorrhage, rheumatism, skin problems, diabetes, and cardiovascular diseases. Recently, brazilin has increased its interest in cancer studies. Several findings have shown that brazilin has cytotoxic effects on colorectal cancer, breast cancer, lung cancer, multiple myeloma, osteosarcoma, cervical cancer, bladder carcinoma, also other cancers, along with numerous facts about its possible mechanisms that will be discussed. Besides its flavonoid content, brazilin is able to chelate metal ions. A study has proved that brazilin could be used as an antituberculosis agent based on its ability to chelate iron. This possible iron-chelating of brazilin and all the studies discussed in this review will lead us to the statement that, in the future, brazilin has the potency to be a chemo-preventive and anticancer agent. The article review aimed to determine the brazilin mechanism and pathogenesis of cancer.

Anti-migratory and cytotoxic effect of indole derivative in C6 glioma cells.

Gliomas are among the most common primary malignant brain tumors. Despite advances in cancer treatment, survival is very low, so the discovery of new therapeutic agents is essential. In this context, indole is an important source for the development of new bioactive molecules. A pharmacological screening of ten indole derivatives was carried out to evaluate the cytotoxic capacity against three tumor cell lines. After pharmacological screening, three compounds were selected, based on their high capacity to reduce cell proliferation, and their IC50 values were determined. Compound 9 exhibited the highest cytotoxic activity (IC50 = 0.4 µg/mL) in gliomas (C6 cell line), and were selected for further experiments. C6 cells were treated with compound 9 to evaluate cellular mechanisms such as colony formation and cell migration capacity and morphological alterations. Compound 9 decreased clone formation (0.4 and 0.8 µg/mL), and inhibited migration (0.2-0.8 µg/mL) in C6 cells. Morphological changes in cells treated with the compound 9 were also observed, such as chromatin condensation, and disorganization in cellular stress beams. Indole derivatives had a cytotoxic effect on tumor cells, and compound 9 showed the best anti-proliferative and anti-migratory activity in glioma cells.

Antiproliferative assay of suma or Brazilian ginseng (Hebanthe eriantha) methanolic extract on HCT116 and 4T1 cancer cell lines, in vitro toxicity on Artemia salina larvae, and antibacterial activity.

Hebanthe eriantha is a medicinal plant used in folk medicine and a subject of commercial interest. The cytotoxicity effects from H. eriantha root extracts on cancerous and normal cells were assessed by the MTT method, and in vitro toxicity was evaluated on Artemia salina. The inhibition of the proliferation of bacteria and MIC values were examined by the disc diffusion and the broth microdilution method, respectively. Human colon cancer HCT116 and mouse breast tumour model 4T1 cells treated with methanolic extract showed a significant decrease in viability of cells with IC50: 272.6 and 88.5 µg/mL at 72h, respectively. The methanolic extract of H. eriantha showed moderate toxicity against A. salina (LC50: 589.4 µg/mL). In antimicrobial activity, the methanolic extract showed the highest inhibitory function against S. aureus and P. vulgaris (17.5 and 16 mm) with MICs of 500 µg/mL. The results confirmed the potential of plant roots as cytotoxic agents.

Study of Cannabis Oils Obtained from Three Varieties of C. sativa and by Two Different Extraction Methods: Phytochemical Characterization and Biological Activities.

Currently, much effort is being placed into obtaining extracts and/or essential oils from Cannabis sativa L. for specific therapeutic purposes or pharmacological compositions. These potential applications depend mainly on the phytochemical composition of the oils, which in turn are determined by the type of C. sativa and the extraction method used to obtain the oils. In this work, we have evaluated the contents of secondary metabolites, delta-9-tetrahydrocannabinol (THC), and cannabidiol (CBD), in addition to the total phenolic, flavonoids, and anthraquinone content in oils obtained using solid-liquid extraction (SLE) and supercritical fluid extraction (SCF). Different varieties of C. sativa were chosen by using the ratio of THC to CBD concentrations. Additionally, antioxidant, antifungal and anticancer activities on different cancer cell lines were evaluated in vitro. The results indicate that oils extracted by SLE, with high contents of CBD, flavonoids, and phenolic compounds, exhibit a high antioxidant capacity and induce a high decrease in the cell viability of the tested breast cancer cell line (MCF-7). The observed biological activities are attributed to the entourage effect, in which CBD, phenols and flavonoids play a key role. Therefore, it is concluded that the right selection of C. sativa variety and the solvent for SLE extraction method could be used to obtain the optimal oil composition to develop a natural anticancer agent.

The Role of Propolis as a Natural Product with Potential Gastric Cancer Treatment Properties: A Systematic Review.

Gastric cancer is one of the most common, aggressive, and invasive types of malignant neoplasia. It ranks fifth for incidence and fourth for prevalence worldwide. Products of natural origin, such as propolis, have been assessed for use as new complementary therapies to combat cancer. Propolis is a bee product with antiproliferative and anticancer properties. The concentrations and types of secondary metabolites contained in propolis mainly vary according to the geographical region, the season of the year, and the species of bees that make it. The present study is a systematic review of the main articles related to the effects of propolis against gastric cancer published between 2011 and 2021 in the PubMed and Science Direct databases. Of 1305 articles published, only eight studies were selected; among their principal characteristics was the use of in vitro analysis with cell lines from gastric adenocarcinoma and in vivo murine models of the application of propolis treatments. These studies suggest that propolis arrests the cell cycle and inhibits proliferation, prevents the release of oxidizing agents, and promotes apoptosis. In vivo assays showed that propolis decreased the number of tumors by regulating the cell cycle and the expression of proteins related to apoptosis.

Sulfated Polysaccharide Extracted from the Green Algae Codium bernabei: Physicochemical Characterization and Antioxidant, Anticoagulant and Antitumor Activity.

Codium bernabei is a green alga that grows on Chilean coasts. The composition of its structural polysaccharides is still unknown. Hence, the aim of this work is to isolate and characterize the hot water extracted polysaccharide fractions. For this purpose, the water extracts were further precipitated in alcohol (TPs) and acid media (APs), respectively. Both fractions were characterized using different physicochemical techniques such as GC-MS, GPC, FTIR, TGA, and SEM. It is confirmed that the extracted fractions are mainly made of sulfated galactan unit, with a degree of sulfation of 19.3% (TPs) and 17.4% (ATs) and a protein content of 3.5% in APs and 15.6% in TPs. Other neutral sugars such as xylose, glucose, galactose, fucose, mannose, and arabinose were found in a molar ratio (0.05:0.6:1.0:0.02:0.14:0.11) for TPs and (0.05:0.31:1.0:0.03:0.1:0.13) for ATs. The molecular weight of the polysaccharide samples was lower than 20 kDa. Both polysaccharides were thermally stable (Tonset > 190 °C) and showed antioxidant activity according to the ABTS•+ and DPPH tests, where TPs fractions had higher scavenging activity (35%) compared to the APs fractions. The PT and APTTS assays were used to measure the anticoagulant activity of the polysaccharide fractions. In general, the PT activity of the TPs and APs was not different from normal plasma values. The exception was the TPs treatment at 1000 µg mL−1 concentration. The APTTS test revealed that clotting time for both polysaccharides was prolonged regarding normal values at 1000 µg mL−1. Finally, the antitumor test in colorectal carcinoma (HTC-116) cell line, breast cancer (MCF-7) and human leukemia (HL-60) cell lines showed the cytotoxic effect of TPs and APs. Those results suggest the potential biotechnological application of sulfate galactan polysaccharides isolated from a Chilean marine resource.

Cytotoxic Effect In Vitro of Acalypha monostachya Extracts over Human Tumor Cell Lines.

Acalypha monostachya (A. monostachya) is a plant that is used in traditional medicine as a cancer treatment; however, its effect has not been validated. In this study, the potential cytotoxic effects and morphological changes of A. monostachya were evaluated in human tumor cell lines. The aqueous (AE), methanolic (ME), and hexane (HE) extracts were obtained, and flavonoid-type phenolic compounds were detected, which indicates an antineoplastic effect. We observed a time-dependent and concentration-selective toxicity in human tumor cells. Additionally, the ME and HE showed the greatest cytotoxic effect at minimum concentrations compared to the AE, which showed this effect at the highest concentrations. All extracts induced significant morphological changes in tumor cells. The HeLa (cervix carcinoma) cells were more sensitive compared to the MDA-MB-231 (triple-negative breast cancer) cells. In conclusion, we demonstrated a cytotoxic in vitro effect of A. monostachya extracts in tumoral human cell lines. These results show the potential antineoplastic effects of A. monostachya in vitro. Hereafter, our lab team will continue working to usefully isolate and obtain the specific compounds of A. monostachya extracts with cytotoxic effects on tumor cells to find more alternatives for cancer treatment.

Biomedical application of graphitic carbon nitrides: tissue depositionin vivo, induction of reactive oxygen species (ROS) and cell viability in tumor cells.

The urgency for new materials in oncology is immediate. In this study we have developed the g-C3N4, a graphitic-like structure formed by periodically linked tris-s-triazine units. The g-C3N4has been synthesized by a simple and fast thermal process. XRD has shown the formation of the crystalline sheet with a compacted structure. The graphite-like structure and the functional groups have been shown by Raman and FTIR spectroscopy. TEM image and AFM revealed the porous composed of five or six C-N layers stacked. DRS and Photoluminescence analyses confirmed the structure with band gap of 2.87 eV and emission band at 448 nm in different wavelengths excitation conditions. The biological results showed inhibitory effect on cancer cell lines and non-toxic effect in normal cell lines. To the best of our knowledge, this is the first work demonstrating the cytotoxic effects of 2D g-C3N4in a cancer cell line, without any external or synergistic influence. The biodistribution/tissue accumulation showed that g-C3N4present a tendency to accumulation on the lung in the first 2 h, but after 24 h the profile of the biodistribution change and it is found mainly in the liver. Thus, 2D-g-C3N4showed great potential for the treatment of several cancer types.

Chemical structure of native and modified sulfated heterorhamnans from the green seaweed Gayralia brasiliensis and their cytotoxic effect on U87MG human glioma cells.

A water-soluble sulfated heterorhamnan (Gb1) was isolated from the green seaweed Gayralia brasiliensis and purified by ultrafiltration, yielding a homogeneous polysaccharide (Gb1r). Both fractions contained rhamnose, xylose, galacturonic and glucuronic acids, galactose, and glucose. Chemical and spectroscopic methods allowed the determination of Gb1 and Gb1r chemical structure. Their backbones were constituted by 3-, 2-, and 2,3-linked rhamnosyl units (1:0.49:0.13 and 1:0.58:0.17, respectively), which are unsulfated (13.5 and 14.6%), disulfated (16.6 and 17.8%) or monosulfated at C-2 (8 and 8.6%) and C-4 (24.5 and 23.4%). Gb1 was oversulfated giving rise to Gb1-OS, which presented ~2.5-fold higher content of disulfated rhamnosyl units than Gb1, as determined by methylation analyses and NMR spectroscopy. Gb1 and Gb1-OS potently reduced the viability of U87MG human glioblastoma cells. Gb1 caused cell cycle arrest in the G1 phase, increased annexin V-stained cells, and no DNA fragmentation, while Gb1-OS increased the percentage of cells in the S and G2 phases and the levels of fragmented DNA and cells double-stained with annexin V/propidium iodide, suggesting an apoptosis mechanism. The results suggest that the different effects of Gb1 and Gb1-OS were related to differences in the sulfate content and position of these groups along the polysaccharide chains.

Aislamiento de Escherichia coli productora de toxina Shiga (STEC) en heces de ganado y detección de factores de virulencia asociados con su patogénesis / Isolation of Shiga toxin-producing Escherichia coli (STEC) in cattle stool and detection of virulence factors associated with its pathogenesis

Resumen Objetivo: Aislar STEC en las heces del ganado bovino en el municipio de Ulloa, Valle del Cauca y detectar factores de virulencia asociados con la patogénesis. Materiales y métodos: Se tomaron 21 muestras provenientes de bovinos, las cuales fueron tomadas directamente del recto del animal mediante hisopos. Las muestras se procesaron hasta obtener colonias puras a las cuales se les evaluó la presencia de los genes stx1, stx2, eae, saa y hlyA mediante PCR y posteriormente, se evaluó el efecto citotóxico de las muestras positivas sobre células Vero (ATCC-CCL-81.4). Resultados: De las 21 muestras de heces de bovinos,12 presentaron bacterias con uno o ambos genes stx. Se obtuvieron 106 aislamientos totales de STEC y se observaron diferencias en cuanto a la presencia y ausencia de los genes de virulencia evaluados en los aislamientos de cada bovino, obteniendo cinco combinaciones de genes. 48 aislamientos presentaron únicamente el gen stx2 y 58 presentaron tanto el gen stx1 como el gen stx2; de los 106 aislamientos, se detectaron 44 con el gen hlyA y 57 con el gen saa. Conclusiones: Todos los sobrenadantes de STEC analizados mostraron actividad citotóxica sobre las células Vero, mientras que en ausencia de STEC las células formaron monocapa después de 48 h de incubación. Este trabajo es el primer reporte en Colombia que aporta información sobre la presencia de STEC en el ganado bovino, la presencia de factores de virulencia y el potencial efecto citotóxico que poseen estas cepas nativas.

Abstract Objective: To isolate STEC in stool samples from cattle in Ulloa, Valle del Cauca, and to detect virulence factors associated with its pathogenesis. Materials and methods: We took 21 samples from cattle, which were taken directly from the rectum of the animal using swabs. The samples were processed until obtaining pure colonies and evaluated for the presence of the stx1, stx2, eae, saa and hlyA genes by PCR. Afterward, the cytotoxic effect of positive samples were evaluated on Vero cells (ATCC-CCL- 81.4). Results: We observed that from the 21 stools samples, 12 presented bacteria with one or both stx genes. A total of 106 isolates of STEC were obtained and differences among each other were observed regarding the presence and absence of the virulence genes, obtaining five combinations of genes. We found that 48 isolates presented only stx2 gene and 58 presented both the stx1 and stx2 gene. Regarding the other virulence genes, the hlyA gene was detected in 44 isolates and the saa gene was detected in 57 isolates. Conclusions: All the STEC supernatants showed cytotoxic activity on Vero cells, while in its absence the cells formed monolayer after 48 h of incubation. This work is the first report in Colombia that provides information about the presence of STEC in stool cattle, virulence genes and its potential cytotoxic effect in native strains.

Pathways Related to the Anti-Cancer Effects of Metabolites Derived from Cerrado Biome Native Plants: An Update and Bioinformatics Analysis on Oral Squamous Cell Carcinoma.

BACKGROUND: Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases. OBJECTIVE: The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells. METHODS: Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards. RESULTS: The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation. CONCLUSION: Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts.

Ocotea porosa: Anatomy and Histochemistry of Leaves and Stems, Chemical Composition, Cytotoxicity and Insecticidal Activities of Essential Oil

Abstract Ocotea porosa (Nees & Mart.) Barroso, commonly known as "imbuia", "canela-imbuia" or "imbuia-amarela" in Brazil, is a tree of the Southern Atlantic Forest. The present study investigates the anatomy of leaf and stem, volatile oil chemistry, as well as cytotoxicity and insecticidal activities of the essential oil of O. porosa. Species identification was achieved by anatomy features, mainly due to paracytic and anomocytic stomata; non-glandular trichomes; biconvex midrib and petiole with a collateral open arc vascular bundle; presence of a sclerenchymatous layer, starch grains and crystal sand in the stem; and the presence of phenolic compounds in the epidermis, phloem and xylem of the midrib, petiole and stem. The main volatile components of the essential oil were α-pinene (19.71%), β-pinene (13.86%) and bicyclogermacrene (24.62%). Cytotoxicity against human cancer cell (MCF-7), mouse cancer cell (B16F10) and mouse non-tumoral cell (McCoy) was observed as well as insecticidal activity of the essential oil against susceptible 'Ft. Dix' bed bugs (Cimex lectularius L.) by topical application.

In vitro antioxidant and antiproliferative effect of the extracts of Ephedra chilensis K Presl aerial parts.

BACKGROUND: Ephedra chilensis K Presl, known locally as pingo-pingo, is a Chilean endemic plant used in traditional medicine as an anti-inflammatory and used in other treatments. However, unlike for the other Ephedra species, there have been no reports on the antioxidant and cytotoxic effects of this plant. The present study aims to explore the potential applications of E. chilensis extract as a cytotoxic agent against in vitro cancer cell lines and to explore the relationship between this extract and antioxidant activity. METHODS: Total anthraquinone, flavonoid, and phenolic contents, as well as antioxidant activity (DPPH, FRAP, and TRAP assays) and cytotoxic effect on several cancer cell lines (MCF-7, PC-3, DU-145, and HT-29) were measured for the hexane, dichloromethane and ethanol extracts of E. chilensis. In addition, several correlations among the phytochemical content, antioxidant activity, and cytotoxic effect were evaluated. Finally, GC-MS analyses of the most active extracts were carried out to identify their major components and to relate these components to the cytotoxic effect. RESULTS: Antioxidant activity was found in the EtOH extracts of Ephedra, and the results were correlated with the phenolic content. For the cytotoxic activity, the non-polar extracts of E. chilensis had the highest antiproliferative effect for the MCF-7 and PC-3 cancer lines; the extract was shown to be up to three times more selective than doxorubicin. However, the cytotoxic effect was not correlated with the antioxidant activity. Lastly, the GC-MS analysis showed a high concentration of saturated fatty acids (mainly n-hexadecanoic acid) and terpenoids (mainly 4-(hydroxy-ethyl)-γ-butanolactone). CONCLUSION: The cytotoxic activity and selectivity of the non-polar extracts of E. chilensis for the MCF-7 and PC-3 cell lines could be related to the terpenic compounds and fatty acids of the extracts or to the synergistic effect of all of the compounds in the extracts. These non-polar extracts can be used for the development of new drugs against breast and prostate cancer.

Antioxidant and cytotoxic properties of protein hydrolysates obtained from enzymatic hydrolysis of Klunzinger's mullet (Liza klunzingeri) muscle

Today, consumers are looking for functional foods that promote health and prevent certain diseases in addition to provide nutritional requirements. This study aimed to evaluate the antioxidant and cytotoxic properties of Liza klunzingeri protein hydrolysates. Fish protein hydrolysates (FPHs) were prepared from L. klunzingeri muscle using enzymatic hydrolysis with papain at enzyme/substrate ratios of 1:25 and 1:50 for 45, 90 and 180 min. The antioxidant activities of the FPHs were investigated through five antioxidant assays. The cytotoxic effects on 4T1 carcinoma cell line were also evaluated. The amino acid composition and molecular weight distribution of the hydrolysate with the highest antioxidant activity were determined by HPLC. All six FPHs exhibited good scavenging activity on ABTS (IC50=0.60-0.12 mg/mL), DPPH (IC50= 3.18-2.08 mg/mL), and hydroxyl (IC50=4.13-2.07 mg/mL) radicals. They also showed moderate Fe+2 chelating capacity (IC50=2.12-12.60 mg/mL) and relatively poor ferric reducing activity (absorbance at 70 nm= 0.01-0.15, 5 mg/mL). In addition, all hydrolysates showed cytotoxic activities against the 4T1 cells (IC50=1.62-2.61 mg/mL). 94.6% of peptide in hydrolysate with the highest antioxidant activity had molecular weight less than 1,000 Da. L. klunzingeri protein hydrolysates show significant antioxidant and anticancer activities in vitro and are suggested to be used in animal studies.

The Cytotoxic and Antimigratory Activity of Brazilin-Doxorubicin on MCF-7/HER2 Cells.

Purpose: Breast cancer cells with overexpression of HER2 are known to be more aggressive, invasive, and resistant to chemotherapeutic agent. Brazilin, the major compound in the Caesalpinia sappan L. (CS) heartwood, has been studied for it's anticancer activity. The purpose of this study was to investigate the cytotoxic and antimigratory activity of brazilin (Bi) in combination with doxorubicin (Dox) on MCF-7/HER2 cells. Methods: Cytotoxic activities of Bi individually and in combination with Dox were examined by MTT assay. Synergistic effects were analyzed by combination index (CI). Apoptosis and cell cycle profiles were observed by using flow cytometry. Migrating and invading cells were observed by using a Boyden chamber assay. Levels of MMP2 and MMP9 activity were observed by using a gelatin zymography assay. Levels of HER2, Bcl-2, Rac1, and p120 protein expression were observed by using an immunoblotting assay. Results: The results of the MTT assay showed that Bi inhibited MCF-7/HER2 cell growth in a dose-dependent manner with an IC50 of 54 ± 3.7 µM. Furthermore, the combination of Bi and Dox showed a synergistic effect (CI <1). Flow cytometric analysis of Bi and its combination with Dox showed cellular accumulation in the G2/M phase and induction of apoptosis through suppression of Bcl-2 protein expression. In the Boyden chamber assay, gelatin zymography, and subsequent immunoblotting assay, the combination Bi and Dox inhibited migration, possibly through downregulation of MMP9, MMP2, HER2, Rac1, and p120 protein expression. Conclusion: We conclude that Bi enhanced cytotoxic activity of Dox and inhibited migration of MCF-7/HER2 cells. Therefore, we believe that it has strong potential to be developed for the treatment of metastatic breast cancer with HER2 overexpression.

Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines.

Linear, dimeric, tetrameric, and cyclic peptides derived from lactoferricin B, containing the RRWQWR motif, were designed, synthesized, purified, and characterized using RP-HPLC chromatography and MALDI-TOF mass spectrometry. The antibacterial activity of the designed peptides against E. coli (ATCC 11775 and 25922) and their cytotoxic effect against MDA-MB-468 and MDA-MB-231 breast cancer cell lines were evaluated. Dimeric and tetrameric peptides showed higher antibacterial activity in both bacteria strains than linear peptides. The dimeric peptide (RRWQWR)2K-Ahx exhibited the highest antibacterial activity against the tested bacterial strains. Furthermore, the peptides with high antibacterial activity exhibited significant cytotoxic effect against the tested breast cancer cell lines. This cytotoxic effect was fast and dependent on the peptide concentration. The tetrameric molecule containing RRWQWR motif has an optimal cytotoxic effect at a concentration of 22 µM. The evaluated dimeric and tetrameric peptides could be considered as candidates for developing new therapeutic agents against breast cancer. Polyvalence of linear sequences could be considered as a novel and versatile strategy for obtaining molecules with high anticancer activity.

Cytotoxic Effect of Thymus caramanicus Jalas on Human Oral Epidermoid Carcinoma KB Cells

Abstract Identifying new chemotherapeutic agents with fewer side effects is a major concern for scientists today. Thymus caramanicus Jalas (Lamiaceae family) is one of the species of Thymus that grows wild in different regions of Iran. Traditionally, leaves of this plant are used in the treatment of diabetes, arthritis and cancer. Here was investigated the cytotoxic property of Thymus caramanicus essential oil and extract in human oral epidermoid carcinoma KB cells. Cell viability was measured by MTT and neutral red assays. The cells were exposed to different concentrations of essential oil (0.05-1 µL/mL) and extract (25-150 µg/mL) for 24 h. Doxorubicin was used as anticancer control drug. The data showed that the essential oil (IC50=0.44 µL/mL) and extract (IC50=105 µg/mL) induce potent cytotoxic property. Surprisingly, cytotoxic effects of essential oil and extract of this plant on KB cancer cells were greater than those on normal gingival HGF1-PI1 cell line. In addition, Thymus caramanicus could potentiate the effect of doxorubicin in sub-effective concentrations. The results of the present study indicate that essential oils and extracts of Thymus caramanicus have potential anti-proliferative property on KB cells and can be used as pharmaceutical case study for oral cancer treatments.

Resumo A identificação de novos agentes quimioterápicos com menos efeitos colaterais é uma grande preocupação para os cientistas de hoje. Thymus caramanicus Jalas (família Lamiaceae) é uma das espécies de Thymus que cresce selvagem em diferentes regiões do Irã. Tradicionalmente, as folhas desta planta são utilizados no tratamento da diabetes, artrite e câncer. Aqui investigamos a propriedade citotóxica do óleo essencial e extrato de Thymus caramanicus em células da linhagem celular tumoral humana de carcinoma epidermóide de boca (KB). A viabilidade celular foi medida por ensaios MTT e vermelho neutro. As células foram expostas a diferentes concentrações de óleo essencial (0,05-1 μL/mL) e extrato (25-150 μg/mL) durante 24 h. A doxorrubicina foi utilizada como droga de controle anticâncer. Os dados mostraram que o óleo essencial (IC50 = 0,44 μL/mL) e o extrato (IC50 = 105 μg/mL) induzem uma potente propriedade citotóxica. Surpreendentemente, os efeitos citotóxicos de óleo essencial e extrato desta planta sobre células cancerígenas KB foram maiores que sobre a linhagem celular gengival normal HGF1-PI1. Além disso, Thymus caramanicus poderia potencializar o efeito da doxorrubicina em concentrações sub-efetivas. Os resultados do presente estudo indicam que óleos essenciais e extratos de Thymus caramanicus têm potenciais propriedades anti-proliferativas sobre células KB e podem ser usado como estudos de caso farmacêuticos para tratamentos de câncer bucal

Preclinical trial on the use of doxycycline for the treatment of adenocarcinoma of the duodenum.

Adenocarcinoma of the duodenum comprises 50-70% of duodenal tumors. There is an increase in extracellular matrix metalloproteinases in this disease and it has been suggested that they play an important role in the development and pathology. Therefore, new therapeutic recommendations based on inhibitors of these enzymes, such as doxycycline, are under investigation. The cytotoxic effect of doxycycline was evaluated in the HuTu-80 duodenal adenocarcinoma cell line and its antitumor effect was determined in an immunodeficient murine model. A 10-µM (4.4 µg/ml) concentration of doxycycline was capable of causing apoptosis in 90% of the culture cells. Doxycycline was also responsible for a decrease in tumor growth and an increase in the survival of the mice with HuTu-80-cell tumors. These results suggest that doxycycline is a potential cytotoxic and antitumor agent effective in the treatment of adenocarcinoma of the duodenum.

Neolignans from Nectandra megapotamica (Lauraceae) Display in vitro Cytotoxic Activity and Induce Apoptosis in Leukemia Cells.

Nectandra megapotamica (Spreng.) Mez. (Lauraceae) is a well-known Brazilian medicinal plant that has been used in folk medicine to treat several diseases. In continuation of our ongoing efforts to discover new bioactive natural products from the Brazilian flora, this study describes the identification of cytotoxic compounds from the MeOH extract of N. megapotamica (Lauraceae) leaves using bioactivity-guided fractionation. This approach resulted in the isolation and characterization of eight tetrahydrofuran neolignans: calopeptin (1), machilin-G (2), machilin-I (3), aristolignin (4), nectandrin A (5), veraguensin (6), ganschisandrin (7), and galgravin (8). Different assays were conducted to evaluate their cytotoxic activities and to determine the possible mechanism(s) related to the activity displayed against human leukemia cells. The most active compounds 4, 5 and 8 gave IC50 values of 14.2 ± 0.7, 16.9 ± 0.8 and 16.5 ± 0.8 µg/mL, respectively, against human leukemia (HL-60) tumor cells. Moreover, these compounds induced specific apoptotic hallmarks, such as plasma membrane bleb formation, nuclear DNA condensation, specific chromatin fragmentation, phosphatidyl-serine exposure on the external leaflet of the plasma membrane, cleavage of PARP as well as mitochondrial damage, which as a whole could be related to the intrinsic apoptotic pathway.