Cyclopentadienyl‐Based Anticancer Drugs: Improvement of Cytotoxic Activity through Functionalisation of the π Ligand

Abstract To investigate which anticancer drugs and combination of dual drugs could further promote the inhibition of cell growth in vitro against HCC cell line (HepG2) in the hypoxic and hyponutritional culture medium (HHCM) mimicked the different scenarios of transcatheter arterial chemoembolization (TACE). The cells of hepatocellular carcinoma (HCC) treated by TACE suffered various hypoxia and hyponutrition. The cells were treated for 2 hours, 4 hours, 6 hours, and 24 hours, respectively, using 10 drugs including epirubicin (EPI), cisplatin (DDP), mitomycin-C (MMC), oxaliplatin (OXA), hydroxycamptothecin (HCPT), 5-fluorouracil (5-FU), gemcitabine (GEM), docetaxel (DTX), thiotepa (TSPA), and pemetrexed disodium (PEM) in 4 concentrations of HHCM (5%, 10%, 25%, and 50%, respectively) mimicking the scenario of TACE and were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells treated with combinations of dual drugs for 24 hours were also tested. The sensitive drugs with inhibition rates more than 30% were EPI, MMC, HCPT, OXA, and PEM in 4 types of HHCMs. The sensitivity of the cells to treatment with drugs for 24 hours was significantly higher than the sensitivity of the cells to treatment with drugs for 2 hours in 5%, 10%, and 25% HHCM. The sensitivity of the combination of dual drugs was no more than the sensitivity of the single drug with higher sensitivity in 4 concentrations of HHCM. EPI, MMC, HCPT, OXA, and PEM exhibited cytotoxic activity against HepG2 cells in various hypoxia and hyponutrition states. Prolonging the time of exposure could increase the sensitivity of drug, and the combination of dual drugs cannot enhance the cytotoxic effect.

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Ferritin Nanocages for Protein Delivery to Tumor Cells

Molecules ◽

10.3390/molecules25040825 ◽

2020 ◽

Vol 25 (4) ◽

pp. 825

Author(s):

Federica Palombarini ◽

Elisa Di Fabio ◽

Alberto Boffi ◽

Alberto Macone ◽

Alessandra Bonamore

Keyword(s):

Cytotoxic Activity ◽

Tumor Cells ◽

Anticancer Drugs ◽

Protein Delivery ◽

Archaeoglobus Fulgidus ◽

Physiological Conditions ◽

Spherical Structure ◽

Small Proteins ◽

Cytotoxic Proteins

The delivery of therapeutic proteins is one of the greatest challenges in the treatment of human diseases. In this frame, ferritins occupy a very special place. Thanks to their hollow spherical structure, they are used as modular nanocages for the delivery of anticancer drugs. More recently, the possibility of encapsulating even small proteins with enzymatic or cytotoxic activity is emerging. Among all ferritins, particular interest is paid to the Archaeoglobus fulgidus one, due to its peculiar ability to associate/dissociate in physiological conditions. This protein has also been engineered to allow recognition of human receptors and used in vitro for the delivery of cytotoxic proteins with extremely promising results.

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Determination of Cytotoxic Activity of Sanguinaria canadensis Extracts against Human Melanoma Cells and Comparison of Their Cytotoxicity with Cytotoxicity of Some Anticancer Drugs

Molecules ◽

10.3390/molecules26061738 ◽

2021 ◽

Vol 26 (6) ◽

pp. 1738

Author(s):

Tomasz Tuzimski ◽

Anna Petruczynik ◽

Tomasz Plech ◽

Barbara Kaproń ◽

Anna Makuch-Kocka ◽

...

Keyword(s):

Cytotoxic Activity ◽

Cell Lines ◽

Anticancer Drugs ◽

Plant Material ◽

Melanoma Cells ◽

Human Melanoma ◽

Sanguinaria Canadensis ◽

Human Melanoma Cells ◽

Ic50 Values

Melanoma is an enormous global health burden, and should be effectively addressed with better therapeutic strategies. Therefore, new therapeutic agents are needed for the management of this disease. The aim of this study was the investigation of cytotoxic activity of some isoquinoline alkaloid standards and extracts obtained from Sanguinaria canadensis—collected before, during, and after flowering—against three different human melanoma cells (A375, G361, SK-MEL-3). The cytotoxicity of these extracts was not previously tested on these melanoma cell lines. Determination of alkaloid contents was performed by HPLC-DAD using Polar RP column and mobile phase containing acetonitrile, water, and 1-butyl-3-methylimidazolium tetrafluoroborate. The cytotoxicity of alkaloid standards was investigated by determination of cell viability and calculation of IC50 values. Significant differences were observed in the alkaloids content and cytotoxic activity of the extracts, depending on the season of collection of the plant material. In the Sanguinaria canadensis extracts high contents of sanguinarine (from 4.8543 to 9.5899 mg/g of dry plant material) and chelerythrine (from 42.7224 to 6.8722 mg/g of dry plant material) were found. For both of these alkaloids, very high cytotoxic activity against the tested cell lines were observed. The IC50 values were in the range of 0.11–0.54 µg/mL for sanguinarine and 0.14 to 0.46 µg/mL for chelerythrine. IC50 values obtained for Sanguinaria canadensis extracts against all tested cell lines were also very low (from 0.88 to 10.96 µg/mL). Cytotoxic activity of alkaloid standards and Sanguinaria canadensis extracts were compared with the cytotoxicity of anticancer drugs—etoposide, cisplatin, and hydroxyurea. In all cases except the one obtained for cisplatin against A375, which was similar to that obtained for Sanguinaria canadensis after flowering against the same cell line, IC50 values obtained for anticancer drugs were higher than the IC50 values obtained for sanguinarine, chelerythrine, and Sanguinaria canadensis extracts. Our results showed that Sanguinaria canadensis extracts and isoquinoline alkaloids, especially sanguinarine and chelerythrine, could be recommended for further in vivo experiments in order to confirm the possibility of their application in the treatment of human melanomas.

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The Anticancer Activity of Srikaya Leaves Fraction (Annona squamosa L.): An In Vitro Study

BioScientia Medicina ◽

10.32539/bsm.v3i4.102 ◽

2019 ◽

Vol 3 (4) ◽

pp. 39-44

Author(s):

Makbruri Amin ◽

Irsan Saleh ◽

Rachmat Hidayat

Keyword(s):

Cytotoxic Activity ◽

Anticancer Activity ◽

Anticancer Drugs ◽

T Test ◽

Therapeutic Effects ◽

Annona Squamosa ◽

Methanol Fraction ◽

T47d Cells ◽

Average Percentage ◽

Ic50 Value

Abstract Introduction: Anticancer drugs are aimed primarily at inhibiting the growth and proliferation of cancer cells. Srikaya leaves (Annona squamosa L.) had been proven to possess various therapeutic effects and potential to be developed as anticancer drugs due to its cytotoxic activity. Aim of study: This study aimed to assess the anticancer activity of srikaya leaves (Annona squamosa L.) fraction. Methods: Methanol fraction of srikaya leaves were obtained at concentrations of 500; 250; 125; 62.5; 31.25 Âµg/ml. Srikaya methanol fraction and cisplatin as control were given to a plate that was sealed with T47D cells for MTT assay. Identification of compounds in the methanol fraction of srikaya leaves was performed with thin layer chromatography (TLC). Data were collected in the form of absorbance value and half-maximal inhibitory concentration (IC50) value was determined â€‹â€‹by linear regression. Data analysis was carried out with paired T test, unpaired T test, and ANOVA. Results: Average percentage of T47D cells viability increased with the decrease in the concentration of srikaya methanol fraction. Obtained IC50 value was 174.25 Âµg/ml which was quite active and potential to be developed as an anticancer drug. Methanol fraction of srikaya leaves contained secondary terpenoid metabolites, steroids, phenols, flavonoids, alkaloids and tannins. Flavonoid was the dominant metabolites in phytochemical tests and believed to play a major role in cytotoxic activity of srikaya leaves. Conclusion: Methanol fraction of srikaya leaves possessed the cytotoxic effect on T47D cancer cell line through the role of flavonoid metabolites. Keywords: srikaya, Annona squamosa, anticancer, T47D cells

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CYTOTOXICITY OF Phaleria macrocarpa (Scheff.) Boerl. FRUIT MEAT AND SEED ETHANOL EXTRACT TO MONONUCLEAR PERIFER NORMAL CELL OF HUMAN BODY

Indonesian Journal of Chemistry ◽

10.22146/ijc.21763 ◽

2010 ◽

Vol 6 (2) ◽

pp. 212-218

Author(s):

Endang Astuti ◽

Deni Pranowo ◽

Santi Dwi Puspitasari

Keyword(s):

Cytotoxic Activity ◽

Anticancer Drugs ◽

Human Body ◽

Human Blood ◽

Normal Cell ◽

Ethanol Extract ◽

F Test ◽

Activity Test ◽

Phaleria Macrocarpa

There were many research on Phaleria macrocarpa (Scheff.) Boerl. fruit for its activity as possible anticancer. However, there wasn't investigation that P. macrocarpa seed and fruit meat ethanol extract effect to normal cell. The research was conducted to identify the ethanol extract of P. macrocarpa for cytotoxic activity against mononuclear perifer normal cell of human blood. The research comprised several sections including P. macrocarpa seed and fruit meat maceration with ethanol, and the cytotoxic activity test against mononuclear normal cell. The results showed that the ethanol extract of P. macrocarpa fruit meat and seed was slightly toxic against mononuclear normal cell with the LC50 of 3817.54 μg/mL and 1349.29 μg/mL respectively. Tamoxifen and 5-fluorourasil, anticancer drugs were extremely toxic against mononuclear normal cell giving LC50 of 3.52 μg/mL and 4.05 μg/mL. The ANOVA f-test (P

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Fatty Acid Modification of the Anticancer Peptide LVTX-9 to Enhance Its Cytotoxicity against Malignant Melanoma Cells

Toxins ◽

10.3390/toxins13120867 ◽

2021 ◽

Vol 13 (12) ◽

pp. 867

Author(s):

Fengjiao Li ◽

Saizhi Wu ◽

Ninglin Chen ◽

Jingyu Zhu ◽

Xinxin Zhao ◽

...

Keyword(s):

Fatty Acid ◽

Cytotoxic Activity ◽

Anticancer Drugs ◽

Melanoma Cells ◽

Serum Free Medium ◽

Free Medium ◽

Acid Modification ◽

Anticancer Peptide ◽

Serum Free ◽

Fatty Acid Modification

Spider venom is a valuable resource for the development of novel anticancer drugs. In this study, we focused on novel linear amphipathic α-helical anticancer peptide LVTX-9, which was derived from the cDNA library of the venom gland of the spider Lycosa vittata. The cytotoxicity of LVTX-9 against murine melanoma cells in the range of 1.56–200 μM was tested and found to be significantly lower than those of most anticancer peptides reported. Its IC50 was determined to be 59.2 ± 19.8 μM in a serum or 76.3 ± 12.7 μM in serum-free medium. Fatty acid modification is a promising strategy for improving peptide performance. Therefore, to enhance the cytotoxic activity of LVTX-9, fatty acid modification of this peptide was performed, and five different carbon chain length lipopeptides named LVTX-9-C12-C20 were produced. Among them, the lipopeptide LVTX-9-C18 showed the highest cytotoxic activity in relation to B16-F10 cells, whether in a serum or serum-free medium. Most importantly, the cytotoxic activity of LVTX-9-C18 was improved by about 12.9 times in a serum medium or 19.3 times in a serum-free medium compared to that of LVTX-9. Subsequently, assays including scanning electron microscopy, trypan blue staining, lactate dehydrogenase leakage assay, and hemolytic activity could indicate that the potential direct cell membrane disruption is the main mechanism of LVTX-9-C18 to induce cancer cell death. Furthermore, the LVTX-9-C18 also showed strong cytotoxicity in relation to 3D B16-F10 spheroids, which indicates it might be a promising lead for developing anticancer drugs.

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