Cytotoxic activity of some lichen extracts on murine and human cancer cell lines

Eight lichens were extracted successively with n-hexane, diethyl ether and methanol using a Soxhlet process. The cytotoxic activity of the 24 lichen extracts was evaluated in vitro using two murine (the L1210: lymphocytic leukaemia, and the 3LL: Lewis lung carcinoma) and four human (the K-562: chronic myelogenous leukaemia, the U251: glioblastoma, the DU145: prostate carcinoma, and the MCF7: breast adenocarcinoma) cancer cell lines and non-cancerous cells, the Vero cell line (African green monkey kidney cell line). The MTT assay revealed significant cytotoxicity (IC50 < or = 20 microg/ml) on one of the tested cancer cell lines for at least one extract of each lichen species. Some extracts of Cladonia convoluta, Cladonia rangiformis, Parmelia caperata, Platismatia glauca and Ramalina cuspidata demonstrated interesting activities particularly on human cancer cell lines as good selectivity indices were recorded (SI > 3).     

Cytotoxic activity of flavonoids and extracts from Retama sphaerocarpa Boissier

Seven flavonoids isolated from chloroform, ethyl acetate and butanol extracts, obtained from the aerial parts of Retama sphaerocarpa, have been assessed for cytotoxic activity against three human cancer cell lines: TK-10 (renal adenocarcinoma), MCF-7 (breast adenocarcinoma) and UACC-62 (melanoma), using the SRB assay. All of them, extracts and flavonoids, were actives in, at least, one of the three cell lines at the recommended National Cancer Institute doses. They produce a dose-dependent inhibition of cell growth at concentrations in the 10(-6)-10(-4) M and 25-250 microg/ml range for the flavonoids and extracts respectively, being the flavonol rhamnazin the most cytotoxic.     

Cytotoxic triterpenoids from Erica andevalensis

The cytotoxic activity of two pentacyclic triterpenoids (ursolic acid and alpha-amyrine) isolated from the methanolic extract of the aerial parts from Erica andevalensis, whose structures have been established on the basis of spectroscopic and chemical evidence, has been assessed against three human cancer cell lines, TK-10 (renal adenocarcinoma), MCF-7 (breast adenocarcinoma) and UACC-62 (melanoma), recommended by NCI (National Cancer Institute) and we also evaluated the antimitotic effect in root meristematic cells of Allium cepa. Ursolic acid was found to possess the highest cytotoxic activity.     

Qualitative HPLC‐DAD/ESI‐TOF‐MS Analysis,Cytotoxic, and Apoptotic Effects of Croatian Endemic Centaurea ragusina L. Aqueous Extracts

Centaurea ragusina L., an endemic Croatian plant species, revealed a good cytotoxic activity of aqueous extracts (AE) on human bladder (T24) and human glioblastoma (A1235) cancer cell lines. The chemical constituents were tentatively identified using high performance liquid chromatography HPLC‐DAD/ESI‐TOF‐MS in negative ionization mode. The main compounds of herba extract were sesquiterpene lactones: solstitialin A 3,13‐diacetate and epoxyrepdiolide; organic acid: quinic acid. The main compounds of flower extract were organic acids: quinic acid, citric acid, and malic acid; sesquiterpene lactone: cynaropicrin; phenolic compounds: chlorogenic acid and phenylpropanoid: syringin. The AE of C. ragusina were investigated for correlation of their effects on human bladder (T24) and human glioblastoma (A1235) cancer cell lines using the MTT assay. Although both extracts showed significant dose‐ and time‐dependent cytotoxic activity against both cancer cell lines, the flower extract exhibited slightly higher activity. In order to determine type of cell death induced by treatment, cell lines were exposed subsequently to a treatment with both flower and herba AE. The majority of the cells died by induced apoptosis treatment. Flower AE (26.25%), compared to a leaf AE (22.15%) showed slightly higher percentage of an apoptosis in T24 cells, when compared to a non‐treated cells (0.04%).     

竹黄菌与竹红菌的化学成分及细胞毒活性比较研究

为研究竹黄菌与竹红菌化学成分及细胞毒活性的差异,本研究通过高效液相色谱(HPLC)分析结合常规色谱方法,分离鉴定了两种真菌的6个相同成分,分别为3个主要成分竹红菌甲素(1)、竹红菌乙素(2)和竹红菌丙素(3),以及3,6,8-三羟基-1-甲基口山酮(7)、3,8-二羟基-6-甲氧基-1-甲基口山酮(8)和过氧麦角甾醇(9)。另外,从竹黄菌中还分离得到11,11′-二去氧沃替西林(5)、麦角甾-7,22E-二烯-3β,5α,6β-三醇(10)和麦角甾-7,22E-二烯-2β,3α,9α-三醇(11),并首次从竹红菌中分离得到竹红菌丁素(4)、灰黄霉素(6)、化合物7和8。活性筛选发现,化合物5对三株肿瘤细胞NCI-H1975、HepG2和MCF-7有很强细胞毒活性,化合物1有较强细胞毒活性,而化合物6活性较弱。     

In vitro cytotoxic activity of extracts and isolated constituents of Salvia leriifolia Benth. against a panel of human cancer cell lines

In the course of recent efforts to identify new potential antiproliferative active principles, Salvia leriifolia extracts and isolated constituents were evaluated for their cytotoxic activity against a panel of human cancer cell lines, including renal adenocarcinoma (ACHN), amelanotic melanoma (C32), colorectal adenocarcinoma (Caco‐2), lung large cell carcinoma (COR‐L23), malignant melanoma (A375), lung carcinoma (A549), and hepatocellular carcinoma (Huh‐7D12) cells. The hexane and CH₂Cl₂ extracts showed the strongest cytotoxic activity against the C32 cell line with IC₅₀ values of 11.2 and 13.6 μg/ml, respectively, and the AcOEt extract was the most active extract against the COR‐L23 cell line (IC₅₀ of 20.9 μg/ml). Buchariol, a sesquiterpene obtained by biofractionation of the CH₂Cl₂ extract, exhibited a higher activity than the positive control vinblastine against the C32 and A549 cell lines (IC₅₀ values of 2.1 and 12.6 μM , resp.). Interesting results were also obtained for naringenin, a flavonoid isolated from the AcOEt extract, which exhibited a strong cytotoxic activity against the C32, LNCaP, and COR‐L23 cell lines (IC₅₀ values of 2.2, 7.7, and 33.4 μM , resp.), compared to vinblastine (IC₅₀ values of 3.3, 32.2, 50.0 μM , resp.). None of the tested compounds affected the proliferation of skin fibroblasts (142BR), suggesting a selective activity against tumor cells.     

In vitro cytostatic and immunomodulatory properties of the medicinal mushroom Lentinula edodes

Lentinula edodes, known as “shiitake” is one of the widely used medicinal mushrooms in the Orient. Antitumour activity of extracts of this mushroom has been widely demonstrated in animals and humans. However, this activity was shown to be host mediated and not by direct cytotoxic activity to cancer cells. This study demonstrates cytotoxic and cell growth inhibitory (cytostatic) effect of aqueous extracts of the mushroom on MCF-7 human breast adenocarcinoma cell line using an MTT cytotoxicity assay. Such effect was demonstrated with fruit body and mycelial extracts, the difference being that there was no significant suppression on normal cells with the latter. Furthermore mycelial extracts did not induce any cytostatic effect in both cancer and normal cell lines based on a DNA synthesis assay. The significant suppression of the proliferation of cancer cells was reflected by the comparatively low IC₅₀ values and the simultaneous higher respective values on normal fibroblast cells. The immunostimulatory activity of both fruit body and mycelial extracts was tested by the lymphocyte transformation test (LTT), which is based on the capacity of active immunomodulators to augment the proliferative response of rat thymocytes to T mitogens in vitro. Both fruit body and mycelial preparations were able to enhance the proliferation of rat thymocytes directly and act as co-stimulators in the presence of the T-mitogen PHA. Interestingly both extracts, similarly to zymosan showed SI_comit/SI_mit ratios of about 2, indicating adjuvant properties. Overall L. edodes aqueous extracts have demonstrated direct inhibition of the proliferation of human breast cancer cells in vitro and immunostimulatory properties in terms of mitogenic and co-mitogenic activity in vitro.     

Cytotoxic activity of halogenated monoterpenes from Plocamium cartilagineum

Nine halogenated monoterpenes isolated from the red alga Plocamium cartilagineum have been evaluated for their cytotoxic effects on the tumor cell lines CT26 (murine colon adenocarcinoma), SW480 (human colon adenocarcinoma), HeLa (human cervical adenocarcinoma) and SkMel28 (human malignant melanoma) with several multidrug resistance mechanisms and the mammalian non-tumor cell line CHO (Chinese hamster ovary cells). The activities of these compounds were compared with those of the insecticide gamma-hexachlorocyclohexane (lindane) due to chemical structure similarities. Compounds 1, 2, 3, and 5 exhibited selective cytotoxicity against colon and cervical adenocarcinoma cells. Interestingly, the effect of compound 3 was specific and irreversible to human colon adenocarcinoma SW480 cells, which overexpress the transmembrane P-glycoprotein often related to chemoresistance. None of the anti-tumor doses of these compounds was cytotoxic against CHO cells. Furthermore, analysis of cellular extracts after incubation with the test compounds and rotenone (positive uptake control) demonstrated the intracellular accumulation of 1, 2, 3, and 5.     

Endophytic Actinobacteria from the Brazilian Medicinal Plant Lychnophora ericoides Mart. and the Biological Potential of Their Secondary Metabolites

Endophytic actinobacteria from the Brazilian medicinal plant Lychnophora ericoides were isolated for the first time, and the biological potential of their secondary metabolites was evaluated. A phylogenic analysis of isolated actinobacteria was accomplished with 16S rRNA gene sequencing, and the predominance of the genus Streptomyces was observed. All strains were cultured on solid rice medium, and ethanol extracts were evaluated with antimicrobial and cytotoxic assays against cancer cell lines. As a result, 92% of the extracts showed a high or moderate activity against at least one pathogenic microbial strain or cancer cell line. Based on the biological and chemical analyses of crude extracts, three endophytic strains were selected for further investigation of their chemical profiles. Sixteen compounds were isolated, and 3‐hydroxy‐4‐methoxybenzamide ( 9 ) and 2,3‐dihydro‐2,2‐dimethyl‐4(1H)‐quinazolinone ( 15 ) are reported as natural products for the first time in this study. The biological activity of the pure compounds was also assessed. Compound 15 displayed potent cytotoxic activity against all four tested cancer cell lines. Nocardamine ( 2 ) was only moderately active against two cancer cell lines but showed strong activity against Trypanosoma cruzi. Our results show that endophytic actinobacteria from L. ericoides are a promising source of bioactive compounds.     

Synthesis and cytotoxic activities of novel copper and silver complexes of 1,3-diaryltriazene-substituted sulfonamides

In this study, a series of 10 novel copper (II) and silver complexes of 1,3-diaryltriazene-substituted sulfonamides was synthesised. All the synthesised ligands and their metal complexes were assessed for in vitro cytotoxicity against human colorectal adenocarcinoma (DLD-1), cervix carcinoma (HeLa), breast adenocarcinoma (MDA-MB-231), colon adenocarcinoma (HT-29), endometrial adenocarcinoma (ECC-1), prostate cancer (DU-145 and PC-3), normal embryonic kidney (HEK-293), normal prostate epithelium (PNT-1A), and normal retinal pigment epithelium (ARPE-19) cells. Most of the metal complexes from the series showed to be more active against all cancerous cells than the uncomplexed 1,3-diaryltriazene-substituted sulfonamides, and lower cytotoxic effects observed on normal cells. Most of the Cu (II) and Ag (I) metal complexes from the presented series showed high cytotoxic activity against HeLa cells with IC₅₀ values ranging from 2.08 to >300?µM. Specifically, compound L₃-Ag showed one of the highest cytotoxicity against all cancer cell lines with IC₅₀ values between 3.30 to 16.18?µM among other tested compounds.     

Base Induced Condensation of Malononitrile with Erlenmeyer Azlactones: An Unexpected Synthesis of Multi‐Substituted Δ2‐Pyrrolines and Their Cytotoxicity

An efficient, metal free approach to synthesize multi‐substituted Δ²‐pyrroline derivatives by mild base catalyzed cyclocondensation of malononitrile with Erlenmeyer azlactones via 1,2 addition was developed. The modularity of this reaction was used to assemble a range of poly‐substituted pyrrolines. Further, synthesized products were screened for cytotoxic properties on different cancer cell lines such as A549 (Human lung adenocarcinoma cells), HeLa (Human cervical adenocarcinoma cells), Jurkat (Human chronic myeloid leukemia cells) and K562 (Human leukemic T cell Lymphoblast cells). Among the synthesized library of compounds, 6f and 6q displayed potent cytotoxic activity.     

Isolation of new cytotoxic metabolites from Cleome droserifolia growing in Egypt

The sulforhodamine B (SRB) assay was used to assess the cytotoxicity of the aqueous (AqEx) and ethanolic (AlEx) extracts, respectively, of the aerial parts of Cleome droserifolia (Forssk.) Del. against two human cancer cell lines, breast (MCF7) and colon (HCT116) adenocarcinoma. AqEx exhibited higher cytotoxic activity, thus its four subfractions, namely n-hexane (HxFr), chloroform (ClFr), ethyl acetate (EtFr), and n-butanol (BuFr) fractions, were also tested. Purification of the more active ClFr and EtFr yielded nine compounds. Six terpenoids, guai-7(11),8-diene (C1), 1-hydroxy-guai-3,10(14)-diene (C2), 18-hydroxydollabela-8(17)-ene (C3), (24E)-stigmasta-5,8-dien-3beta-ol (C4), teucladiol [1alpha,5beta-guai-10(14)-ene-4beta,6beta-diol] (C5), and buchariol (4,10-epoxy-6a-hydroxyguaiane) (C6), were isolated from ClFr and three flavonol glycosides, isorhamnetin-3-O-beta-D-glucoside (F1), quercetin-3'-methoxy-3-O-(4"-acetylrhamnoside)-7-O-alpha-rhamnoside (F2), and kaempferol-4'-methoxy-3,7-O-dirhamnoside (F3), were isolated from EtFr. Compounds C3 and F2 are new in nature. The isolated compounds were identified using various spectroscopic methods (UV, IR, 1H NMR, 13C NMR, HMQC, HMBC, and COSY). Compounds C1, C3, F2, and F3 showed significant cytotoxic activities against the two tested cell lines comparable to those of the anticancer drug doxorubicin. The new compound C3 was the most active as it had the lowest IC50 values, (1.9 +/- 0.08) and (1.6 +/- 0.09) microg/ml corresponding to 6.5 and 5.4 microM, against MCF7 and HCT116 cells, respectively.     

Cytotoxic and antiviral activities of Colombian medicinal plant extracts of the Euphorbia genus

Forty-seven plant extracts of 10 species of the genus Euphorbia (Euphorbiaceae) used by Colombian traditional healers for the treatment of ulcers, cancers, tumors, warts, and other diseases, were tested in vitro for their potential antitumour (antiproliferative and cytotoxic) and antiherpetic activity. To evaluate the capacity of the extracts to inhibit the lytic activity of herpes simplex virus type 2 (HSV-2) and the reduction of viability of infected or uninfected cell cultures, the end-point titration technique (EPTT) and the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] colorimetric assay were used, respectively. The therapeutic index of the positive extracts for the antiviral activity was determined by calculating the ratio CC50 (50% cytotoxic concentration) over IC50 (50% inhibitory concentration of the viral effect). Five of the 47 extracts (11%) representing 3 out of 10 Euphorbia species (30%) exhibited antiherpetic action; the highest activity was found in the leaf/stem water-methanol extracts from E. cotinifolia and E. tirucalli. The therapeutic indexes of these two plant species were > 7.1; these extracts exhibited no cytotoxicity. Six extracts (13%) representing 4 plant species (40%) showed cytotoxic activity. The highest cytotoxicity was found in the dichloromethane extract obtained from E. cotinifolia leaves and the CC50 values for the most susceptible cell lines, HEp-2 and CHO, were 35.1 and 18.1 microgram/ml, respectively.     

Cytotoxic constituents from Brazilian red propolis and their structure-activity relationship

Several classes of flavonoids [flavanoids (1-10), flavonol (11), isoflavones (12-18), isoflavanones (19-22), isoflavans (23-26), chalcones (27-30), auronol (31), pterocarpans (32-37), 2-arylbenzofuran (38), and neoflavonoid (39)] and lignans (40-42) isolated from the MeOH extract of Brazilian red propolis were investigated for their cytotoxic activity against a panel of six different cancer cell lines including murine colon 26-L5 carcinoma, murine B16-BL6 melanoma, murine Lewis lung carcinoma, human lung A549 adenocarcinoma, human cervix HeLa adenocarcinoma, and human HT-1080 fibrosarcoma cell lines. Based on the observed results, structure-activity relationships were discussed. Among the tested compounds, 7-hydroxy-6-methoxyflavanone (3) exhibited the most potent activity against B16-BL6 (IC(50), 6.66microM), LLC (IC(50), 9.29microM), A549 (IC(50), 8.63microM), and HT-1080 (IC(50), 7.94microM) cancer cell lines, and mucronulatol (26) against LLC (IC(50), 8.38microM) and A549 (IC(50), 9.9microM) cancer cell lines. These activity data were comparable to those of the clinically used anticancer drugs, 5-fluorouracil and doxorubicin, against the tested cell lines, suggesting that 3 and 26 are the good candidates for future anticancer drug development.     

Xanthatin and xanthinosin from the burs of Xanthium strumarium L. as potential anticancer agents

Xanthatin and xanthinosin, 2 sesquiterpene lactones isolated from the burs of Xanthiun strumarium L. (cocklebur), showed moderate to high in vitro cytotoxic activity in the human cancer cell lines WiDr ATCC (colon), MDA-MB-231 ATCC (breast), and NCI-417 (lung). Xanthatin and xanthinosin were purified as the result of a multi-screening bioassay-guided study of wild plant species of the family Asteraceae, collected from various sites in Saskatchewan, Canada. Seventy-five extracts at a single concentration of 100 microg/mL were evaluated for in vitro cytotoxicity to the human cancer cell lines used. The chloroform extract of Carduus nutans L. (nodding thistle) aerial parts (IC50, 9.3 microg/mL) and the hexane extract of Echinacea angustifolia DC. (narrow-leaved purple coneflower) root (IC50, 4.0 microg/mL) were moderately to highly cytotoxic to the lung cancer cell line. The chloroform extracts of X. strumarium L. burs and Tanacetum vulgare L. (tansy) aerial parts exhibited the highest cytotoxicity for all cell lines tested; their IC50 values, obtained from multidose testing, ranged from 0.1 to 6.2 microg/mL (X. strumarium) and from 2.4 to 9.1 microg/mL (T. vulgare). Further purification of the chloroform fraction of X. strumarium yielded xanthatin and xanthinosin in high yields. This is the first time that these compounds have been reported in the burs of X. strumarium. Their IC50 values are also reported herein.     

The pharmaceutical exploration of cold water ascidians from the Netherlands: a possible source of new cytotoxic natural products

Six ascidian species from the Dutch North Sea coast were screened for cytotoxic activity. Freeze-dried biological material was extracted with solvents of different polarity followed by determination of the cytotoxicity. The most active extracts were further separated using different chromatographic techniques. The microculture tetrazolium (MTT) assay was used to determine the cytotoxicity against two human tumor cell lines: COLO₃₂₀ (a colon adenocarcinoma) and GLC₄ (a small cell lung carcinoma). The two cell lines were selected for their different response towards known cytostatics. GLC₄ is sensitive and COLO₃₂₀ is resistant to most of the known cytostatics. Three of the species tested yielded interesting fractions. From the in colonial Didemnum lahillei we have isolated a compound which is more active against the COLO₃₂₀ cell line (IC₅₀:33 μg ml⁻¹) than the GLC₄ (IC₅₀:49 μg ml⁻¹). The structure is currently elucidated. Another colonial species, Aplidium glabrum, yielded a very cytotoxic fraction, with an IC₅₀ of 5 μg ml⁻¹ against the COLO₃₂₀ cell line. From our results it can be concluded that the North Sea could be another interesting source of new compounds with pharmaceutical potential.     

Genista sessilifolia DC. and Genista tinctoria L. inhibit UV light and nitric oxide-induced DNA damage and human melanoma cell growth

Many Genista species (Leguminosae), containing isoflavones as biologically active substances, show interesting biological properties such as hypoglycemic, antiinflammatory, antiulcer, spasmolytic, antioxidant, estrogenic and cytotoxic activity against different human cancer cell lines. In this work, we describe the chemical composition of the methanolic extracts from aerial parts of Genista sessilifolia DC. and Genista tinctoria L., and their biological activity testing the effect on pBR322 DNA cleavage induced by hydroxyl radicals (OH), generated from UV-photolysis of hydrogen peroxide (H₂O₂) and by nitric oxide (NO). In addition, we investigated the growth inhibitory activity of these natural products against human melanoma cell line (M14). The extracts of G. sessilifolia and G. tinctoria, for their isoflavone components, showed a protective effect on UV light and nitric oxide-mediated plasmid DNA damage, and inhibited the growth of melanoma cells. The data of the present study also suggest that these natural products could trigger apoptotic death in M14 cells. In fact, a high DNA fragmentation (COMET assay) and a significant increase of caspase-3 activity, not correlated to LDH release, a marker of membrane breakdown, occurred in melanoma cells exposed to these extracts. The significant production of reactive oxygen species (ROS) evidenced in these experimental conditions could contribute to trigger the apoptosis cascades.     

Biological evaluation of some quinoline derivatives with different functional groups as anticancer agents

Due to a great deal of biological activities, quinoline derivatives have drawn attention for synthesis and biological activities in the search for new anticancer drug development. In this work, a variety of substituted (phenyl, nitro, cyano, N‐oxide, and methoxy) quinoline derivatives ( 3 ‐ 13 ) were tested in vitro for their biological activity against cancer cell lines, including rat glioblastoma (C6), human cervical cancer cells (HeLa), and human adenocarcinoma (HT29). 6‐Bromo‐5‐nitroquinoline ( 4 ), and 6,8‐diphenylquinoline (compound 13 ) showed the greatest antiproliferative activity as compared with the reference drug, 5‐fluorouracil (5‐FU), while the other compounds showed low antiproliferative activity. 6‐Bromo‐5‐nitroquinoline ( 4 ) possesses lower cytotoxic activity than 5‐FU in HT29 cell line. Due to its the apoptotic activity 6‐Bromo‐5‐nitroquinoline ( 4 ) has the potential to cause cancer cell death.     

Multidrug resistant cancer cells susceptibility to cytotoxic taxane diterpenes from Taxus yunnanensis and Taxus chinensis

Twelve taxane diterpenes (1-12), which were isolated previously from the EtOH extract of the aerial parts of Taxus yunnanensis or Taxus chinensis, were evaluated for cytotoxicity against the multidrug resistant cancer cells KB-VIN and KB-7d. Compounds and showed significant cytotoxicity in these cell lines. Compounds and also demonstrated significant activity against KB-7d. The biflavonoid isolated from T. yunnanensis was only marginally cytotoxic against the A549 (lung) cell line, but a simple methoxylated analogue (14) was inactive.