Anticancer Cytotoxic Activity Research Articles

Anticancer cytotoxic activity of pentane-2, 4-dione extracted from the leaves of Cordia sebestena

Cervical cancer is a menace to women in the under developed and developing countries. With the population on the rise and with the cervical cancer incidence ever increasing, there is a commensurate need to develop more and more potential anticancer compounds. The aim of the present study was to isolate and to identify the anticancer cytotoxic lead compound from Cordia sebestena leaves. Aqueous, petroleum ether and ethyl acetate extracts prepared from the Cordia sebestena leaves were assessed for their anti-proliferative activity on cervical cancer cells (HeLa) using MTT assay. The active lead present in the petroleum ether extract was separated using preparatory TLC. The structure of the active compound was elucidated by spectroscopic studies using GC-MS, NMR and FT-IR. Docking studies were also performed with the lead compound and cancer target protein using Auto Dock 4.2. Anti-inflammatory of the lead was also performed by LPS induced nitric oxide inhibition assay. Petroleum ether extract showed the IC50 value of 250μg/ml in HeLa cells. Pure compound was identified as pentane-2, 4-dione. Pentane-2, 4-dione demonstratedan IC50 value of 10μg/ml on HeLa cells. In-Silico molecular docking studies demonstrated that Pentane-2, 4-dione showed high-affinity interaction with Kras protein with the least binding energy of-5.15Kcal/mol and 124.37μM as inhibition constant. Pentane-2, 4-Dione (10μg/ml) showed a 47% reduction in nitric oxide production in LPS induced raw macrophages. Based on results, it can be concluded that the anticancer cytotoxic activity of the lead compound pentane-2, 4-dione from C. sebestena is due to its inhibition of Kras protein.

Metal Nanoclusters with Synergistically Engineered Optical and Buffering Activity of Intracellular Reactive Oxygen Species by Compositional and Supramolecular Design

Metal nanoclusters featuring tunable luminescence and high biocompatibility are receiving attention as fluorescent markers for cellular imaging. The recently discovered ability of gold clusters to scavenge cytotoxic reactive oxygen species (ROS) from the intracellular environment extends their applicability to biomedical theranostics and provides a novel platform for realizing multifunctional luminescent probes with engineered anti-cytotoxic activity for applications in bio-diagnostics and conceivably cellular therapy. This goal could be achieved by using clusters of strongly reactive metals such as silver, provided that strategies are found to enhance their luminescence while simultaneously enabling direct interaction between the metal atoms and the chemical surroundings. In this work, we demonstrate a synergic approach for realizing multifunctional metal clusters combining enhanced luminescence with strong and lasting ROS scavenging activity, based on the fabrication and in situ protection of Ag nanoclusters with a supramolecular mantle of thiolated-Au atoms (Ag/Au-t). Confocal imaging and viability measurements highlight the biocompatibility of Ag/Au-t and their suitability as fluorescent bio-markers. ROS concentration tests reveal the remarkable scavenging activity of Ag-based clusters. Proliferation tests of cells in artificially stressed culture conditions point out their prolonged anti-cytotoxic effect with respect to gold systems, ensuring positive cell proliferation rates even for long incubation time.

Elucidating the structural organization of a novel low-density lipoprotein nanoparticle reconstituted with docosahexaenoic acid

Low-density lipoprotein nanoparticles reconstituted with unesterified docosahexaenoic acid (LDL-DHA) is promising nanomedicine with enhanced physicochemical stability and selective anticancer cytotoxic activity. The unique functionality of LDL-DHA ultimately relates to the structure of this nanoparticle. To date, however, little is known about the structural organization of this nanoparticle. In this study chemical, spectroscopic and electron microscopy analyses were undertaken to elucidate the structural and molecular organization of LDL-DHA nanoparticles. Unesterified DHA preferentially incorporates into the outer surface layer of LDL, where in this orientation the anionic carboxyl end of DHA is exposed to the LDL surface and imparts an electronegative charge to the nanoparticles surface. This negative surface charge promotes the monodisperse and homogeneous distribution of LDL-DHA nanoparticles in solution. Further structural analyses with cryo-electron microscopy revealed that the LDL-DHA nanostructure consist of a phospholipid bilayer surrounding an aqueous core, which is distinctly different from the phospholipid monolayer/apolar core organization of plasma LDL. Lastly, apolipoprotein B-100 remains strongly associated with this complex and maintains a discrete size and shape of the LDL-DHA nanoparticles similar to plasma LDL. This preliminary structural assessment of LDL-DHA now affords the opportunity to understand the important structure–function relationships of this novel nanoparticle.

Phytochemical and Biological Investigation of Ipomoea carnea Jacq. Grown in Egypt

Total phenolic and flavonoid contents of the leaves and flowers of Ipomoea carnea Jacq. were carried out using Folin-Ciocalteu’s and aluminum chloride assays, respectively. Resulted in 6.59 and 9.37 mg gallic acid equivalent (GAE)/g. dry wt. and 1.336% and 0.885% rutin equivalent (RE)/g for leaves and flowers, respectively. The concentration of rutin and β-sitosterol in leaves and flowers extracts of I. carnea were also estimated by HPLC analysis resulting in 9.174 and 2.733 mg/g dry wt. (rutin) and 0.463, 17.085 mg/g dry wt. (β-sitosterol) for leaves and flowers, respectively. Chromatographic separation of the leaves and flowers ethanol extracts led to the isolation of a new biflavonoid compound: 3ꞌ, 3ꞌꞌꞌꞌ, 5, 5ꞌꞌꞌ, 7, 7ꞌꞌꞌ-O-β-D-glucosyl-4ꞌ, 4ꞌꞌꞌꞌ-biflavonoyl ether [4ꞌ-O-4ꞌꞌꞌꞌ Bis-isoquercetin] (Ipomoeflavoside) from leaves and other four known compounds namely; caffeoyl ethyl ester, caffeic acid, rutin, lycopene isolated for the first time from leaves and β-sitosterol from flowers. The leaves and flowers ethanol extracts showed antioxidant, antihyperglycemic and hepatoprotective activities. They were also evaluated for their anticancer and antimicrobial activities. The ethanol leaves extract showed the highest cytotoxic activity against the breast cancer cell line, with (IC50: 7.4 µg/ml) while it showed weak cytotoxic effect on liver and colon cancer cell lines (IC50:23 and 35 µg/ml) respectively, The ethanol flowers extract showed weak or no anticancer cytotoxic activity against the tested cancer cell lines. The leaves and flowers ethanol extracts showed significant antimicrobial activity against Streptococcus pneumonia, Bacillus subtillis, Escherichia coli and Aspergillus fumigatus while showing no activity against Candida albicans and Pseudomonas aeurginosa.

Antimutagenic, Antigenotoxic, and Anticytotoxic Activities of Silybum Marianum [L.] Gaertn Assessed by the Salmonella Mutagenicity Assay (Ames Test) and the Micronucleus Test in Mice Bone Marrow

ABSTRACTSilymarin (SM), a standardized extract from Silybum marianum (L.) Gaertn., is composed mainly of flavonolignans, and silibinin (SB) is its major active constituent. The present study aimed to evaluate the antimutagenic activities of SM and SB using the Ames mutagenicity test in Salmonella Typhimurium, as well as their anticytotoxic and antigenotoxic activities using the mouse bone marrow micronucleus test. To assess antimutagenicity, Salmonella Typhimurium strains were treated with different concentrations of SM or SB and the appropriate positive control for each strain. To assess antigenotoxicity and anticytotoxicity, Swiss mice were treated with different concentrations of SM or SB and mitomycin C (MMC). The results showed that SM was not significantly effective in reducing the number of frameshift mutations in strain TA98, while SB demonstrated significant protection at higher doses (P < 0.05). Regarding strain TA 100, SM and SB significantly decreased mutagenicity (point mutations) (P < 0.05). The results of the antigenotoxic evaluation demonstrated that SM and SB significantly reduced the frequency of micronucleated polychromatic erythrocytes (MNPCE) (P < 0.05). The results also indicated that SM and SB significantly attenuated MMC-induced cytotoxicity (P < 0.05). Based on these results, both SM and SB presented antimutagenic, antigenotoxic, and anticytotoxic actions.

Genotoxicity and Cytotoxicity Evaluation of the Neolignan Analogue 2-(4-Nitrophenoxy)-1Phenylethanone and its Protective Effect Against DNA Damage.

Neolignans are secondary metabolites found in various groups of Angiosperms. They belong to a class of natural compounds with great diversity of chemical structures and pharmacological activities. These compounds are formed by linking two phenylpropanoid units. Several compounds that have ability to prevent genetic damage have been isolated from plants, and can be used to prevent or delay the development of tumor cells. Genetic toxicology evaluation is widely used in risk assessment of new drugs in preclinical screening tests. In this study, we evaluated the genotoxicity and cytotoxicity of the neolignan analogue 2-(4-nitrophenoxy)-1-phenylethanone (4NF) and its protective effect against DNA damage using the mouse bone marrow micronucleus test and the comet assay in mouse peripheral blood. Our results showed that this neolignan analogue had no genotoxic activity and was able to reduce induced damage both in mouse bone marrow and peripheral blood. Although the neolignan analogue 4NF was cytotoxic, it reduced cyclophosphamide-induced cytotoxicity. In conclusion, it showed no genotoxic action, but exhibited cytotoxic, antigenotoxic, and anticytotoxic activities.

Anti Cancer, Cytotoxic Activity, Mutagenic and Anti-mutagenic Activities of Artemisia aucheri Essential Oil

The essential oil of Artemisia aucheri Boiss. collected from Khorassan, north east of Iran, was investigated for anti-cancer, cytotoxic, mutagenic and anti-mutagenic activities. Cytotoxicity was measured using a modified MTT assay on normal human lymphocytes and tumor HeLa cells. The IC50 shows that cytotoxicity of the oil in the human tumor cell line than that observed in normal human lymphocytes. The mutagenic and anti-mutagenic activities of the essential oil of A. aucheri was evaluated using the Salmonella typhimurium tester strains TA98 and TA100, together with nitrofluorene for TA98 and sodium azide for TA100 without (-S9) metabolic activation, and 2-aminoantracene for TA98 and TA100 with metabolic (+S9) activation. A. aucheri showed good anti-mutagenic effect against S. typhimurium tester strains TA98 and TA100.

Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test.

Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenyl)prop-2-enoyl]phenyl} benzenesulfonamide (CPN) were assessed using the Salmonella typhimurium reverse mutation test (Ames test) and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05). The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p < 0.05), whereas in strain TA100 this occurred only at doses higher than 50 μg/plate (p < 0.05). The results of the micronucleus test indicated that CPN significantly increased the frequency of micronucleated polychromatic erythrocytes (MNPCE) at 24 h and 48 h, revealing a genotoxic effect of this compound. Also, a significant decrease in polychromatic/normochromatic erythrocyte ratio (PCE/NCE) was observed at the higher doses of CPN at 24 h and 48 h (p < 0.05), indicating its cytotoxic action. CPN co-administered with mitomycin C (MMC) significantly decreased the frequency of MNPCE at almost all doses tested at 24 h (p < 0.05), showing its antigenotoxic activity, and also presented a small decrease in MNPCE at 48 h (p > 0.05). Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties.

ChemInform Abstract: A New Triterpenoid and Potential Anticancer Cytotoxic Activity of Isolated Compounds from the Roots of Eucalyptus citriodora.

AbstractA new triterpenoid, citriodora A (I), is isolated along with five known compounds.

ChemInform Abstract: A New Steroidal Glycoside and Potential Anticancer Cytotoxic Activity of Compounds Isolated from the Bulbs of Lilium callosum.

AbstractThe new steroidal glycoside, callosum A (I), is isolated along with five known steroidal glycosides from the butanol soluble fraction of Lilium callosum.

In vitro study of biological activities of anthocyanin-rich berry extracts on porcine intestinal epithelial cells.

Anthocyanins, compounds that represent the major group of flavonoids in berries, are one of the most powerful natural antioxidants. The aim of this study was to evaluate biological activities and comparison of anthocyanin-rich extracts prepared from chokeberry (Aronia melanocarpa), elderberry (Sambucus nigra), bilberry (Vaccinium myrtillus) and blueberry (V. corymbosum) on the porcine intestinal epithelial IPEC-1 cell line. The IC50 values calculated in the antioxidant cell-based dichlorofluorescein assay (DCF assay) were 1.129 mg L(-1) for chokeberry, 1.081 mg L(-1) for elderberry, 2.561 mg L(-1) for bilberry and 2.965 mg L(-1) for blueberry, respectively. We found a significant negative correlation (P < 0.001) between cyanidin glycosides content and IC50 values. Moreover, extracts rich in cyanidin glycosides stimulated proliferation of IPEC-1 cells and did not have cytotoxic effect on cells at an equivalent in vivo concentration. We found that the chokeberry and elderberry extracts rich in cyanidin glycosides possess better antioxidant and anticytotoxic activities in comparison to blueberry or bilberry extracts with complex anthocyanin profiles.

A New Triterpenoid and Potential Anticancer Cytotoxic Activity of Isolated Compounds from the Roots of Eucalyptus Citriodora

Citriodora A, 3β,25-dihydroxy-5α,6α-epoxy-7-oxocucurbita-(23E)-en-19-al, a new triterpenoid, has been isolated from the roots of Eucalyptus citriodora, together with five known analogues, which were reported for the first time from this plant. The structures were elucidated on the basis of spectral studies including mass spectroscopy and extensive 2D NMR. All components were tested for anticancer cytotoxic activity against osseous tumour cell line.

A New Steroidal Glycoside and Potential Anticancer Cytotoxic Activity of Compounds Isolated from the Bulbs of Lilium Callosum

Callosum A, a new steroidal glycoside, has been isolated from the n-butanol soluble fraction of Lilium callosum, along with five known steroidal glycosides, reported for the first time from Lilium callosum. Their structures were elucidated on the basis of spectroscopic methods and from literature values. All compounds were tested for anticancer cytotoxic activity against GSC-7901, K562, and SPCA-1 cells.

승마갈근탕과 발효 승마갈근탕에 의한 항산화, 항미생물 및 항세포독성 효과

Seungmagalgeuntang (SG) is broadly used in traditional Oriental medicine especially in Korea, China, and Japan, for its many pharmacological effects. This study was carried out to investigate the antioxidative, antimicrobial, and anticytotoxic activities of SG and fermented seungmagalgeuntang (FSG). DPPH radical scavenging activities of SG and FSG were 70% and 74%, respectively, which increased slightly by fermentation. Nitrite scavenging activities were strongly altered at pH 1.2, (36.4% in SG and 38.3% in FSG) by addition of 200 μg/g. Superoxide dismutase-like activities were from 21.5% to 23.3% at a concentration of 0.4 mg/mL, and the highest value were observed in FSG. Total flavonoid contents of SG and FSG were 47.1 and 52.1 μg/L, respectively which shows an increase upon fermentation. In the antimicrobial activity test, MIC50 values of SG and FSG were 800 μg/mL for Candida albicans and 3,200 and 1,600 μg/mL for Staphylococcus epidermidis and Staphylococcus aureus, respectively. Antibacterial effects were higher in FSG compared to SG. Anticytotoxic cadmium toxicities ranged from 63.5% to 76.1% at 10 μg/mL of SG and FSG, and the highest value was observed in FSG. In the sensory evaluation, color, flavor, and overall preference values were higher in FSG.

Genotoxicity and cytotoxicity evaluation of oenothein B and its protective effect against mitomycin C-induced mutagenic action

The natural product oenothein B (OeB), a dimeric macrocyclic ellagitannin, has a wide range of biological activities, such as antioxidant, anti-inflammatory, anti-viral, antifungal, and antitumor. However, investigations concerning its genotoxicity have not been carried out. This study assessed the cytotoxicity, genotoxicity, and protective effects of oenothein B using in vitro SOS-Inductest and in vivo mouse bone marrow micronucleus (MN) assay through oral and intraperitonial routes. In both assays oenothein B did not produce genotoxic effects in any of doses tested; in contrast, cytotoxic effect in cells was detected only in mice groups treated by both routes and exposed for 24 and 48h. Antigenotoxic and anticytotoxic activities of oenothein B were evaluated using both assays in combination with mitomycin C (MMC), a bioreductive alkylating agent. In the MN assay, a significant reduction was observed in MN frequency in all groups co-treated with MMC and OeB compared to those which received only MMC. Anticytotoxicity was observed in mice groups exposed to OeB and MMC for 24 and 48h. In the SOS-Inductest, oenothein B failed to show antigenotoxic and anticytotoxic effects; thus, it undoubtedly showed an in vivo protective activity against primary DNA damage induced by mitomycin C.

Chemical constituents and in vitro anticancer cytotoxic activities of Polyalthia plagioneura

Chemical constituents and in vitro anticancer cytotoxic activities of Polyalthia plagioneura

Investigating the antioxidant and anticytotoxic activities of propolis collected from five regions of Indonesia and their abilities to induce apoptosis

Propolis is a resinous substance collected by stingless bee or honey bee from various plant sources. The substance is known to contain beneficial properties for human. The geographical origin of propolis determines its biological properties. In this study, propolis were collected from five regions of Indonesia with the objective of determining the yield, their total flavonoid content, their capacity to induce apoptosis, and their toxicity to the Michigan Cancer Foundation-7 (MCF-7) cell line. The inhibition of antioxidant 1,1-diphenyl-2-picrylhydrazyl (DPPH), the induction of apoptosis to Saccharomyces cerevisiae and the anticytotoxic ability were determined. Propolis from Pekanbaru region had higher yield than other regions with value of 19.97%; propolis from Kendal had higher quantity with value of 46.60%, total flavonoid content; propolis from Pandeglang was higher in DPPH oxidation capacity with value of 68.94 ?g.ml-1; propolis from Kendal, expressed petite cell induction in S. cerevisiae cells with value of 81.44%, and the anticytotoxic to MCF-7 breast cancer cell line were best observed in propolis from Makassar region with a value of 47.71% life cells. All of the propolis extracted from the stingless bee hive Trigona spp from five regions in Indonesia contained flavonoids.

Antigenotoxic and anticytotoxic activity of Duguetia furfuracea in bacteria and mice

Duguetia furfuracea (St. Hil.) Benth & Hook f. (1862), popularly known as "sofre-do-rim-quem-quer" and "araticum-seco", is a shrub of the Annonaceae family that grows in several regions of Brazil. Infusions of its leaves and twigs are used in folk medicine to treat rheumatism and renal colic, whereas the seed powder is mixed with water to treat pediculosis. Studies on the plant have reported biological activities with cytotoxic, antitumoral, trypanocidal, leishmanicidal, antiplasmodial, and antiprotozoal effects. Our previous studies using a prophage λ induction test (SOS-Inductest) and the micronucleus assay demonstrated that D. furfuracea lyophilized leaf extract (DFE) displayed cytotoxic but not genotoxic activity. In the present study, antigenotoxic and anticytotoxic activities of DFE were evaluated using SOS-Inductest and mouse bone marrow micronucleus tests. Our results showed that DFE decreased the induction of either prophage λ (P < 0.05; SOS-Inductest) or micronucleated polychromatic erythrocytes (P < 0.05; micronucleus test) at all doses, suggesting antigenotoxic activity in both tests. On assessing the anticytotoxic activity of DFE, a significant increase in the number of bacteria at lower doses (P < 0.05) as well as a significant increase in the polychromatic and normochromatic erythrocyte ratio were observed (P < 0.05), demonstrating the anticytotoxic activity of DFE. Thus, D. furfuracea displayed antigenotoxic and anticytotoxic activity in both assays.

Assessment of toxic, genotoxic, antigenotoxic, and recombinogenic activities of Hymenaea courbaril (Fabaceae) in Drosophila melanogaster and mice

Hymenaea courbaril L., popularly known as jatobá, is a plant species that grows in the forests of South America. The species has been used for culinary purposes and in folk medicine to treat arthritis and inflammations. Due to the increasing use of this plant globally, the present study aimed to evaluate the toxic, genotoxic, recombinogenic, and antigenotoxic effects of H. courbaril sap (Hycs) using the mouse bone marrow micronucleus test and the somatic mutation and recombination test (SMART) in Drosophila melanogaster. To evaluate the aneugenic and clastogenic activities revealed by the micronucleus test, the animals were treated with 3 doses of Hycs (5, 10, and 15 mL/kg body weight). To evaluate the antianeugenic and anticlastogenic activities, the animals were simultaneously treated with Hycs and mitomycin C (4 mg/kg body weight). To assess the mutagenic and recombinogenic activities using SMART, 3-day-old larvae derived from standard and high bioactivation crosses were treated with 3 doses of Hycs (3.0, 1.5, and 0.3 mL) for approximately 48 h. To evaluate antimutagenic and antirecombinogenic activities, larvae derived from both crosses were co-treated with 3 doses of Hycs (3.0, 1.5, and 0.3 mL) and doxorubicin (0.125 mg/ mL). The mouse bone marrow micronucleus test revealed that Hycs exhibited no cytotoxic, clastogenic and/or aneugenic effects, but did show anticytotoxic, anticlastogenic and/or antianeugenic activities. The SMART revealed no mutagenic or recombinogenic effects, but antimutagenic and antirecombinogenic activities were observed in somatic cells of D. melanogaster from both crosses.

Antigenotoxic, and anticytotoxic activities of an ethanolic extract of Lafoensia pacari (Lythraceae) stem bark in bacteria and mice

Lafoensia pacari (Lythraceae), popularly known in Brazil as "pacari", is a small tree native to the Cerrado that is used in folk medicine to treat cancer and as an anti-inflammatory and cicatrizing agent. We evaluated the genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of an ethanol extract of L. pacari stem bark (EESB) using the Ames test and the mouse bone marrow micronucleus test. In the Ames test, EESB did not significantly increase the number of His(+) revertants in Salmonella typhimurium tester strains TA98 and TA100 at all doses, demonstrating lack of mutagenicity. Only the highest dose of EESB significantly increased the micronucleated polychromatic erythrocyte frequency in the micronucleus test, indicating mild genotoxicity. EESB produced a mutagenic index lower than the negative control in the Ames test. In the micronucleus test, at all doses, EESB caused a significant decrease in the polychromatic/normochromatic erythrocyte ratio (PCE/NCE) at 24 h compared with the negative control. EESB co-administered together with the respective positive control caused a significant decrease in the number of His(+) revertant colonies in the Ames test and in the frequency of micronucleated polychromatic erythrocytes in the micronucleus test, demonstrating a DNA protector effect. EESB co-administered with mitomycin C significantly increased the PCE/NCE ratio at all doses, showing an anticytotoxic effect. We conclude that EESB has antigenotoxic and anticytotoxic properties.