Globally, peptide-based anticancer therapies have drawn much attention. Marine organisms are a reservoir of anticancer peptides that await discovery. In this study, we aimed to identify cytotoxic oligopeptides from Sarcophyton glaucum. Peptides were purified from among the S. glaucum hydrolysates produced by alcalase, chymotrypsin, papain, and trypsin, guided by a methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay on the human cervical cancer (HeLa) cell line for cytotoxicity evaluation. Purification techniques adopted were membrane ultrafiltration, gel filtration chromatography, solid phase extraction (SPE), and reversed-phase high-performance liquid chromatography (RP-HPLC). Purified peptides were identified by de novo peptide sequencing. From papain hydrolysate, three peptide sequences were identified: AGAPGG, AERQ, and RDTQ (428.45, 502.53, and 518.53 Da, respectively). Peptides synthesized from these sequences exhibited cytotoxicity on HeLa cells with median effect concentration (EC₅₀) values of 8.6, 4.9, and 5.6 mmol/L, respectively, up to 5.8-fold stronger than the anticancer drug 5-fluorouracil. When tested at their respective EC₅₀, AGAPGG, AERQ, and RDTQ showed only 16%, 25%, and 11% cytotoxicity to non-cancerous Hek293 cells, respectively. In conclusion, AERQ, AGAPGG, and RDTQ are promising candidates for future development as peptide-based anticancer drugs.
Amino Acid Sequence ; Animals ; Anthozoa/chemistry* ; Antineoplastic Agents/pharmacology* ; Chromatography, Gel ; Chromatography, High Pressure Liquid ; Chromatography, Reverse-Phase ; Cytotoxins/pharmacology* ; Drug Discovery ; HEK293 Cells ; HeLa Cells ; Humans ; Hydrolysis ; Marine Toxins/pharmacology* ; Oligopeptides/pharmacology* ; Solid Phase Extraction ; Tandem Mass Spectrometry

OBJECTIVETo determine the medicinal potential of various plants and their parts extracted with different solvents.

METHODSThe total phenolic content of acetonitrile/water (60%-40%) (ACN/W) and aqueous (W) extract fractions was determined by high-performance liquid chromatography (HPLC), and terpenic compounds were detected by gas chromatography/mass spectrometry (GC/MS). Antioxidant activity of the samples was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and β-carotene bleaching method. Cell viability was investigated by thiazolyl blue tetrazolium bromide [3-(4,5-dimethylthiazol)-2-yl 2,5-diphenyltetrazolium bromide] (MTT) assay. The mechanisms involved in cytotoxic activity were investigated in a murine macrophage cell line (RAW 264.7) and cancer lines.

RESULTSOur findings show that 11 plant species exhibited biological activity. In addition, moderate antibacterial activity was reported against one or more of the tested bacterial strains at two concentrations: 300 μg and 3 mg/disc. Furthermore, our data reveal that among all plants investigated, some extract and hydrophobic fractions were potent scavengers of the DPPH radical (6.78 μg/mL < EC50 < 8.55 μg/mL). Taken together, our results show that Nerium oleander (NOACN/W) and Pituranthos tortuosus (PTACN/W) were highly cytotoxic against RAW 264.7 cells with IC80 values of 0.36, and 1.55 μg/mL, respectively. In contrast, murine macrophage cell lines had low growth and were significantly sensitive to water extracts of Thymus hirtus sp. algeriensis (THW), Lavandula multifida (LMW), and ACN/W extract of Erica multiflora (EMACN/W) at doses > 400, 47.20, and 116.74 μg/mL, respectively. The current work demonstrates that RAW 264.7 cell proliferation was inhibited by samples in a dose-dependent manner.

CONCLUSIONOur findings, validated through free radical scavenging activity, agar diffusion assay, and cytotoxicity of essential oils towards cancer cells, show that ethnomedicinal plants used in this work have a novel application as a tumor suppressor.

Animals ; Anti-Bacterial Agents ; chemistry ; pharmacology ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; Bacteria ; drug effects ; Biphenyl Compounds ; Cell Line ; Cytotoxins ; chemistry ; pharmacology ; Ethnobotany ; Mice ; Molecular Structure ; Phenols ; chemistry ; pharmacology ; Picrates ; Plant Extracts ; chemistry ; pharmacology ; Plants, Medicinal ; chemistry ; Terpenes ; chemistry ; pharmacology ; Tunisia

The chemical consitituents from cytotoxic fraction of the Callicarpa nudiflora extract were isolated and purified by a combination of HP-20 macroporous resin, silica gel and Sephadex LH-20 column chromatographies. The structures were elucidated on the basis of the spectroscopic data and comparison of their spectroscopic data with reported data. The cytotoxicity was evaluated by the MTT assay. The 50% and 70% EtOH elutions of EtOH-extract showed significant cytotoxic activities, leading to the isolation of twelve compounds, which were identified as luteoloside(1), lutedin-4'-O-β-D-glucoside(2), 6-hydroxyluteolin-7-O-β-glucoside(3), lutedin-7-O-neohesperidoside(4), rhoifolin (5), luteolin-7, 4'-di-O-glucoside (6), forsythoside B (7), acteoside (8), alyssonoside (9), catalpol(10), nudifloside(11), and leonuride(12). Compounds 3-6, 10 and 12 were isolated from this genus for the first time, and compound 9 was isolated from this plant for the first time. The cytotoxicity assay demonstrated that flavonoids 1-6, in various concentrations, showed monolithic proliferation inhibitory activities against Hela, A549 and MCF-7 cell lines. Compounds 3, 5 and iridoid glycoside 11 possessed higher cytotoxicacivities. In short, flavonoids are the main components of cytotoxic extract from C. nudiflora, while phenylethanoid glycosides are the predominant ingredient but inactive to cancer cell lines. In addition, the minor iridoid glycoside expressed weak cytotoxic activity.
Callicarpa ; chemistry ; Cell Proliferation ; drug effects ; Cytotoxins ; chemistry ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; pharmacology ; Humans ; MCF-7 Cells ; Molecular Structure

Chemotherapy remains one of the major tools, along with surgery, radiotherapy, and more recently targeted therapy, in the war against cancer. There have appeared a plethora of highly potent cytotoxic drugs but the poor discriminability between cancerous and healthy cells of these agents limits their broader application in clinical settings. Therapeutic antibodies have emerged as an important class of biological anticancer agents, thanks to their ability in specific binding to tumor-associated antigens. While this important class of biologics can be used as single agents for the treatment of cancer through antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is often limited. Antitumor antibody drug conjugates (ADCs) combine the target-specificity of monoclonal antibody (mAb) and the highly active cell-killing drugs, taking advantages of the best characteristics out of both components. Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to transport potent payloads to tumor cells. ADCs contain three main components: antibody, linker and cytotoxics (also frequently referred as payload). Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release. While ADC has demonstrated tremendous success, a number of practical challenges limit the broader applications of this new class of anticancer therapy, including inefficient cellular uptake, low cytotoxicity, and off-target effects. This review article aims to cover recent advances in optimizing linkers with increased stability in circulation while allowing efficient payload release within tumor cells. We also attempt to provide some practical strategies in resolving the current challenges in this attractive research area, particularly to those new to the field.
Aminobenzoates ; pharmacology ; therapeutic use ; Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Cell Survival ; drug effects ; Cytotoxins ; pharmacology ; therapeutic use ; Drug Design ; Humans ; Immunoconjugates ; chemistry ; pharmacology ; therapeutic use ; Maytansine ; pharmacology ; therapeutic use ; Neoplasms ; drug therapy ; pathology ; Oligopeptides ; pharmacology ; therapeutic use

Viburnum odoratissimum is a folk medicinal plant, it can dredge the meridian passage and contains mainly diterpenes, triterpenes, flavonoids, sesquiterpenes, lignans, coumarin glycosides, etc. Vibsanin-type diterpenoids are the characteristic compounds of V. odoratissimum, and are divided into eleven-membered ring, seven-membered ring, and rearrangement-type. Vibsanin B, vibsanin C and neovibsanin A are the representative compounds of the three subtypes of vibsanin-type diterpenoids respectively. V. odoratissimum has cytotoxic activity, antibacterial activity, fish piscicidal activity and activity of inhibiting the growth of plants, Cytotoxic activity is the main biological activity.
Animals ; Antineoplastic Agents, Phytogenic ; chemistry ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cytotoxins ; chemistry ; isolation & purification ; pharmacology ; Diterpenes ; chemistry ; isolation & purification ; pharmacology ; Flavonoids ; chemistry ; isolation & purification ; Humans ; Lignans ; chemistry ; isolation & purification ; Molecular Structure ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry ; Triterpenes ; chemistry ; isolation & purification ; pharmacology ; Viburnum ; chemistry

OBJECTIVETo investigate the antioxidant and cytotoxic activity of the flower of Acanthus ilicifolius (A. ilicifolius).

METHODSAntioxidant activity was determined as antiradical efficiency with diphenyl picrylhydrazil (DPPH) method and cytotoxic assay was undertaken using brine shrimp lethal toxicity test.

RESULTSA. ilicifolius flower contained terpenoid, phenolic compounds, and alkaloid. The methanol extract of A. ilicifolius flower showed the highest antiradical efficiency (AE=1.41×10(-3)) against DPPH radicals and the highest cytotoxicity (LC50=22 µg/mL) against brine shrimp nauplii.

CONCLUSIONSIt is suggested that active compounds of A. ilicifolius flower solved in methanol play a role to inhibit free radical activity and kill Artemia salina nauplii. The substances can be considered as potential antioxidant and cytotoxic agents as well as imminent candidate for cancer therapy.

Acanthaceae ; chemistry ; Animals ; Antioxidants ; pharmacology ; Artemia ; drug effects ; Biphenyl Compounds ; chemistry ; pharmacology ; Cytotoxins ; toxicity ; Flowers ; chemistry ; Lethal Dose 50 ; Picrates ; chemistry ; pharmacology ; Plant Extracts ; chemistry ; pharmacology

OBJECTIVETo study the effect of anticolchicine cytotoxicity of Dan Gua-Fang, a Chinesea Chinese), a Chinese herbal compound prescription on endothelial cells of vein (ECV304) cultivated in mediums of different glucose concentrations as well as the proliferation of those cells in the same conditions, in order to reveal the value of Dan Gua-Fang in preventing and treating endothelial damage caused by hyperglycemia in diabetes mellitus.

METHODSThe research was designed as three stages. The growing state and morphological changes were observed when ECV304 were cultivated in the culture mediums, which have different glucose concentrations with or without Dan Gua-Fang and at the same time with or without colchicine.

RESULTS(1) Dan Gua-Fang at all concentrations reduced the floating cell population of ECV304 cultivated in hyperglycemia mediums. (2) Dan Gua-Fang at all concentrations and hyperglycemia both had a function of promoting "pseudopod-like" structure formation in cultivated ECV304, but the function was not superimposed in mediums containing both hyperglycemia and Dan Gua-Fang. (3) Colchicine reduced and even vanished the "pseudopod-like" structure of the endotheliocyte apparently cultivated in mediums of hyperglycemia or with Dan Gua-Fang. The "pseudopod-like" structure of the endotheliocyte emerged quickly in Dan Gua-Fang groups after colchicine was removed, but it was not the case in hyperglycemia only without Dan Gua-Fang groups. (4) Dan Gua-Fang reduced the mortality of cells cultivated in mediums containing colchicine. The cell revived to its normal state fast after colchicine was removed.

CONCLUSIONDan Gua-Fang has the functions of promoting the formation of cytoskeleton and fighting against colchicine cytotoxicity.

Cell Culture Techniques ; Cell Line ; Cell Shape ; drug effects ; Colchicine ; adverse effects ; antagonists & inhibitors ; Culture Media ; adverse effects ; pharmacology ; Cytoprotection ; drug effects ; Cytotoxins ; adverse effects ; antagonists & inhibitors ; Drug Antagonism ; Drug Combinations ; Drug Evaluation, Preclinical ; Drug Synergism ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Endothelial Cells ; drug effects ; physiology ; Glucose ; pharmacology ; Humans ; Umbilical Veins ; cytology ; drug effects ; Up-Regulation

OBJECTIVETo study the selective cytotoxic effect of lentivirus-mediated double suicide gene (CD/TK) against human gastric carcinoma cells SGC-7901 in vitro.

METHODSSGC-7901 cells were infected with FGW-KDRP-CD/TK vector and the infection efficiency was observed under a fluorescence microscope. The morphological changes of the infected cells were observed by Giemsa staining. Flow cytometry (FCM) was employed for cell cycle analysis, and the expression of CD/TK was detected by RT-PCR. The infected cells were then treated with the prodrugs ganciclovir (GCV) and/or 5-fluorocytosine (5-FC) at different concentrations, and the cytotoxic effects were evaluated using MTT method.

RESULTSThe infection efficiency of the lentiviral vector in SGC-7901 cells increased with the titer of the virus, which produced no significant effect on the cancer cell morphology in vitro or on the percentages of G0-G1, G2-M and S phase cells (P>0.05). RT-PCR demonstrated the expression of CD/TK gene in SGC-7901 cells infected by FGW-KDRP-CD/TK. The infected cells were highly sensitive to the prodrugs with a dose-dependent cytotoxic effect within a specific concentration range of the drugs, whereas the non-infected cells were not sensitive to the prodrugs. Combined use of the two prodrugs produced an obviously stronger inhibitory effect than either of the them (P<0.05). When combined, GCV and 5-FC at the concentration of 0.1+40, 1+80, 10+160, and 100+320 mg/L demonstrated a synergetic effect with a CDI<1.

CONCLUSIONLentivirus-mediated CD/TK fusion gene system can selectively kill gastric cancer cells, and the two prodrugs show a synergistic cytotoxic effect.

Adenocarcinoma ; genetics ; pathology ; Cell Line, Tumor ; Cytosine Deaminase ; biosynthesis ; genetics ; Cytotoxins ; pharmacology ; Genes, Transgenic, Suicide ; genetics ; Genetic Therapy ; Genetic Vectors ; genetics ; Humans ; Lentivirus ; genetics ; metabolism ; Recombinant Fusion Proteins ; biosynthesis ; genetics ; pharmacology ; Stomach Neoplasms ; genetics ; pathology ; Thymidine Kinase ; biosynthesis ; genetics ; Vascular Endothelial Growth Factor Receptor-2 ; genetics ; metabolism

OBJECTIVETo investigate the antioxidant and cytotoxic properties of five diarylheptanoids (1-5) isolated from the rhizomes of Zingiber officinale.

METHODVarious models such as scavenging superoxide anions and 1,1-diphenyl-2- picrylhydrazyl (DPPH) radicals, inhibiting lipid peroxidation, as well as protecting of rat pheochromocytoma (PC12) cells induced by hydrogen peroxide (H2O2) were employed to assay the antioxidative effects of the diarylheptanoids. The cytotoxicities of compounds 1-5 were measured with MTT assays.

RESULTThe test compounds (1-5) showed promising DPPH inhibitory activities, and compound 5 exhibited the strongest DPPH scavenging activity with an IC50 value of (22.6+/-2.4) micromol x L(-1). Compounds 1, 3 and 4 showed potential anti-peroxidative effects with inhibitory rates of (66.3+/-15.4)%, (68.7+/-15.8)% and (72.2+/-10.6)%, respectively, at 100 microg x mL(-1). It could be observed that compounds 1, 3 and 4 demonstrated significant neuroprotective activities in a dose-dependent manner. Moreover, compound 3 exhibited certain cytotoxicities against human chronic myelogenous leukemia cells (K562) and its adriamycin-resistant cells (K562/ADR) with IC50 values of (34.9+/-0.6), (50.6+/-23.5) micromol x L(-1), respectively.

CONCLUSIONIn vitro results demonstrated that five diarylheptanoids (1-5) isolated from the roots of Z. officinale were capable of scavenging radicals, inhibiting lipid peroxidation and protecting PC12 cells against the insult by H2O2. Additionally, compound 3 could inhibit the growth of K562 and K562/ADR cells.

Animals ; Antioxidants ; toxicity ; Cell Proliferation ; drug effects ; Cytotoxins ; toxicity ; Diarylheptanoids ; isolation & purification ; metabolism ; toxicity ; Free Radicals ; metabolism ; Ginger ; chemistry ; Humans ; Hydrogen Peroxide ; metabolism ; K562 Cells ; Oils, Volatile ; pharmacology ; PC12 Cells ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore a new specific therapy of nasopharyngeal carcinoma (NPC) using an anti-nasopharyngeal carcinoma (NPC) monoclonal antibody BAC5 conjugate with Chinese cobra (CT) and iodine-131(131I).

METHODSBAC5 was labeled with 131I by chloramine-T method, CT was labeled with 125I using iodogen method, and BAC5 and 125I-CT were conjugated by SPDP method. The inhibitory effect of the conjugate on cultured human NPC CNE2 cells was observed using MTT assay.

RESULTSThe IC50 of 125I-CT-BAC5 conjugate was 9.17x10(-8) mol/L, and that of 131I-BAC5 was 5.83x10(8) Bq/L, and their combined administration showed obvious inhibitory effect on the NPC cells.

CONCLUSIONBoth 125I-CT-BAC5 and 131I-BAC5 have obvious inhibition effects against NPC cells, but their combined use shows stronger effects.

Animals ; Antibodies, Monoclonal ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cytotoxins ; pharmacology ; Elapid Venoms ; pharmacology ; Humans ; Immunoconjugates ; pharmacology ; Iodine Radioisotopes ; pharmacology ; Nasopharyngeal Neoplasms ; pathology