Liver Cancer Cell Line HepG2 Research Articles

Kaempferitrin-Treated HepG2 Differentially Expressed Exosomal Markers and Affect Extracellular Vesicle Sizes in the Secretome.

Kaempferitrin is extracted in significantly high quantities from the leaves of Cinnamomum osmophloeum, which belongs to a group of plant species that comes under the genus Cinnamomum, well-known for its established anti-diabetic property in Chinese medicine. Oral administration of kaempferitrin and Cinnamomum osmophloeum extract reduced blood sugar in alloxan-induced diabetic rats and improved the lipid profile in hamsters respectively. In this paper we studied the differential protein expression profile using mass spectrometry approach in the kaempferitrin-treated conditioned medium of liver cancer cell line HepG2. We discovered that 33 genes were up/down-regulated consistently between two biological samples. A slightly different version of the analysis software selected 28 genes, and the final 18 genes that appeared in both lists were selected. Interestingly, 5 proteins out of 18 were either exosomal markers or reported in high frequency of occurrence in exosome/secreted vesicles. We also examined the extracellular particles with atomic force microscopy (AFM), which showed that the conditioned medium of kaempferitrin treated had larger vesicles and fewer small vesicles. Expression of some lipid-regulating genes were also altered. Our data suggested that extracellular vesicle secretions may be regulated by kaempferitrin, and regulation of lipid profile by kampeferitrin involves multiple mechanisms.

New 1,2,3-Triazole-Containing Hybrids as Antitumor Candidates: Design, Click Reaction Synthesis, DFT Calculations, and Molecular Docking Study.

In an effort to improve and achieve biologically active anticancer agents, a novel series of 1,2,3-triazole-containing hybrids were designed and efficiently synthesized via the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction of substituted-arylazides with alkyne-functionalized pyrazole-[1,2,4]-triazole hybrids. The structure geometry of these new clicked 1,2,3-triazoles was explored by density functional theory (DFT) using the B3LYP/6-311++G(d,p) level; also, the potential activity of the compounds for light absorption was simulated by time-dependent DFT calculations (TD-DFT). The antitumor impacts of the newly synthesized compounds were in vitro estimated to be towards the human liver cancer cell line (HepG-2), the human colon cancer cell line (HCT-116), and human breast adenocarcinoma (MCF-7). Among the tested compounds, conjugate 7 was the most potent cytotoxic candidate towards HepG-2, HCT-116, and MCF-7, with IC50 = 12.22, 14.16, and 14.64 µM, respectively, in comparison to that exhibited by the standard drug doxorubicin (IC50 = 11.21, 12.46, and 13.45 µM). Finally, a molecular docking study was conducted within the epidermal growth factor receptor (EGFR) active site to suggest possible binding modes. Hence, it could conceivably be hypothesized that analogies 7, 6, and 5 could be considered as decent lead candidate compounds for anticancer agents.

Visualization of the Oncolytic Alphavirus M1 Life Cycle in Cancer Cells.

Oncolytic alphavirus M1 has been shown to selectively target and kill cancer cells, but cytopathic morphologies induced by M1 virus and the life cycle of the M1 strain in cancer cells remain unclear. Here, we study the key stages of M1 virus infection and replication in the M1 virus-sensitive HepG2 liver cancer cell line by transmission electron microscopy, specifically examining viral entry, assembly, maturation and release. We found that M1 virus induces vacuolization of cancer cells during infection and ultimately nuclear marginalization, a typical indicator of apoptosis. Specifically, our results suggest that the endoplasmic reticulum participates in the assembly of nucleocapsids. In the early and late stage of infection, three kinds of special cytopathic vacuoles are formed and appear to be involved in the replication, maturation and release of the virus. Taken together, our data displayed the process of M1 virus infection of tumor cells and provide the structural basis for the study of M1 virus-host interactions.

Cytotoxicity Effect of the Pericarp Extracts of Garcinia forbesii King on MCF-7 Breast Cancer and HepG2 Liver Cancer Cell Lines

Background: The species from the genus Garcinia has long been used as traditional medicine for cancer treatment. Objective: To analyze the phytochemical contents and assess the cytotoxic effects of pericarp extracts of Garcinia forbesii King against MCF-7 breast cancer cells and HepG2 liver cancer cells. Materials and Methods: The phytochemical contents were analyzed using the thin-layer chromatography and the cytotoxic activity was assessed using the MTT assay method. Results: Phytochemical screening showed the presence of alkaloids, flavonoids, terpenoids and polyphenols. The cytotoxic activities of n-hexane, DCM and ethyl acetate extracts on MCF-7 cells were shown with IC50 103.605±2.3410 μg/ mL, 397.609±28.0534 μg/mL and 1,518.301±68.6379 μg/mL respectively, while the IC50 on HepG2 cells were 79.798±1.2261 μg/mL, 83.230±4.2557 μg/mL and 671.875±94.3338 μg/mL respectively. Conclusion: The n-hexane, DCM and ethyl acetate extracts from pericarps of G. forbesii King have cytotoxic activities against MCF-7 and HepG2 cancer cells, therefore, it has the potential to be developed as an anticancer.

Cytotoxic activity of Green Zinc Selenide Nanoparticles Against Hep-G2 Cell Lines

In the current study a new technique between the plasma physics, nanoparticle and Biotechnology,structured(ZnSe) prepared by cold plasma technique using atmospheric pressure plasmajet system, Znse NPs wereprepared from selenium nitrate and zinc metal sheets to reduce selenium toxicity. The structural and opticalproperties were characterized by X-ray diffraction (XRD) and absorbance measurements of ZnSe greenNPs. The liver cancer cell line (hepG2) was exposed to the ZnSe nanoparticles, and The percentage ofcytotoxicity was suppressed after 24, and48 from exposure, induced cytotoxicity is found to be 70.3% inhepG2 after exposed 48h ZnSe green nanoparticle, and the maximum cytotoxicity of the normal cell line(REF) was also examined 42.62% when exposure ZnSe nanoparticles and 16.6% when exposure ZnSe greennanoparticles.

The Comparative Effect of Nisin and Thioridazine as Potential Anticancer Agents on Hepatocellular Carcinoma.

Hepatocellular carcinoma is a major health problem worldwide especially in Egypt. It accounts for the fifth common cancer and the second cause of death among different cancers. This study investigated the efficacy and molecular mechanism of Nisin and/or Thioridazine as anticancer treatment on human liver cancer HepG2 cell line. Nisin and Thioridazine were applied for 24 h on human liver cancer cell line (HepG2). 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was done to assess the cytotoxicity of Nisin and Thioridazine. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was used for the assessment of PI3K, AKT, SIRT-1, and NRF2 expression in the treated cell line. The protein level of reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF) was measured in the collected media by ELISA technique. Western blot analysis was done for, tAKT, pAKT, tPI3K, and pPI3K. Cell proliferation results showed that compared with the untreated cancer, Nisin and/or Thioridazine treated groups had decreased cell proliferation (p value< 0.0001). Nisin and/or Thioridazine decreased PI3K/AKT mRNA and protein expression in hepatocellular carcinoma cells (HCC). Also Nisin and/or Thioridazine decreased anti-oxidative SIRT1/NRF2 mRNA expression. ROS level highly increased with Nisin and/or Thioridazine treatment in contrast to VEGF protein level which was highly decreased. These results introduce Nisin and Thioridazine as new therapeutic lines in HCC.

In-vitro Cytotoxic Activity of Oleanolic &amp; Cincholic acids isolated from Lotus glaber-mill herb (Family, Fabaceae)

In the current study, antiproliferative effects of 3 s- hydroxyl- Olean - 12 - en - 28 - oic acid (Oleanolic acid ; OA) & 3-s-hydroxyolean - 12-en–27, 28 dioic acid (Cincholic acid; CA); triterpene sapogenins isolated from the ethyl-acetate fraction of Lotus glaber-mill herb were evaluated against three human cancer cell lines, the liver cancer cell line( HepG-2), the colon cancer cell line (HCT-116), & the breast cancer cell line (MCF-7). The structures of isolated phytoconstituents were identified by careful analysis of 1D NMR spectra and negative ESI-MS data. Oleanolic acid & Cincholic acid displayed cytotoxic activities against the tested cell lines. Oleanolic acid has lower IC50 than Cincholic acid for both MCF-7 & HCT-116 at 27.99 & 18.66µg/ml respectively.While Cincholic acid has a lower IC50 in HEPG-2 than Oleanolic acid at 22.81µg/ml. Further investigations have shown that Oleanolic acid & Cincholic acid- induce apoptosis and cause cell cycle arrest at the G2/M phase.

Sensitive MnFe2O4-Ag hybrid nanoparticles with photothermal and magnetothermal properties for hyperthermia applications.

In this study, we present an experiment showing that designing multifunctional MnFe2O4–Ag nanoparticles to act as a dual hyperthermia agent is an efficient route for enhancing their heating ability. Interestingly, the specific absorption rate of the heteromeric MnFe2O4–Ag nanoparticles increased 2.7 times under simultaneous irradiation of a 100 Oe magnetic field and 0.14 W cm−2 laser compared to the action by the magnetic field alone, and more interestingly, is 30% higher than the sum of the two individual actions. The synergistic benefit of the magneto- and photo-thermal properties of the heteromeric structure can reduce the strengths of the magnetic field and laser intensities as well as their irradiation time to levels lower than those required in their hyperthermia applications individually. In vitro cytotoxicity analysis performed on HepG2 liver cancer and Hela cervical cancer cell lines showed that IC50 values were 83 ± 5.6 μg mL−1 (for HepG2) and 122.6 ± 19.8 μg mL−1 (for Hela cells) after 48 h of incubation, therefore, the nanoparticles are moderately cytotoxic and nontoxic to HepG2 and Hela cells, respectively; which offers the potential of safe therapy.

Hypoxia as a modulator of cytochromes P450: Overexpression of the cytochromes CYP2S1 and CYP24A1 in human liver cancer cells in hypoxia.

Low levels of oxygen (hypoxia) have been reported in solid tumours. This hypoxic microenvironment modulates the expression of genes linked to a more aggressive disease. However, it is unclear if the expression of drug-metabolizing enzymes as cytochromes P450 (CYPs) is affected by hypoxia in cancer. We aimed to define which cytochromes are affected by hypoxia using a liver cancer model in vitro. For this purpose, we assessed whole-genome expression microarrays of HepG2 liver cancer cell line from free repository databases, looking for gene expression hypoxia-associated profiles and selected those cytochromes with significant differences. Then, we corroborated their mRNA expression and protein levels by RT-qPCR and western blot, respectively, as well as immunofluorescence. Based on microarray analysis, we found that the expression of CYP2S1 and CYP24A1 were up-regulated with at least twice fold change compared with normoxia. The levels of mRNA and protein of CYP2S1 and CYP24A1 were increased significantly in hypoxic conditions (P < .05), and this tendency was also observed by immunofluorescence assays. Our data show that the expression of cytochromes CYP2S1 and CYP24A1 are induced in hypoxia, being the first time that CYP24A1 expression is associated with tumour hypoxia; which might have consequences in cancer progression and drug resistance. SIGNIFICANCE OF THE STUDY: Hypoxia is among the most important factors for cellular adaptation to stress. Especially in cancer, a major public health issue, hypoxia plays a substantial role in angiogenesis, metastasis and resistance to therapy. Tumoral hypoxia has been described at least in the brain, breast, cervical, liver, renal, lung, pancreatic and renal cancer. However, the understanding of how hypoxia drives cancer progression is still a major challenge. One emerging question is the role of hypoxia over the expression of drug-metabolizing enzymes, with a significant impact on drug treatment. In this context, our paper focus on the effect of hypoxia on CYPs, which is an essential group of drug-metabolizing enzymes. We show that hypoxia induces the expression of two members of the CYPs family: CYP2S1 and CYP24A1. Importantly, CYP2S1 is a major metabolizer of carcinogenic substances being relevant that hypoxia could promote this function. Interestingly, CYP24A1 limits the action of the active form of vitamin D, which is an anti-proliferative factor in cancer. Our evidence shows for the first time that hypoxia can induce CYP24A1 expression, with a potential effect on cancer progression. Our contribution clarifies a particular effect of tumoral hypoxia and the implications will be useful in the understanding of the progression of cancer, the resistance to treatment and the development of alternative therapies.

Design, Synthesis and Biological Evaluation of Cyanopyridines, Pyridopyrazolopyrimidines and Pyridopyrazolotriazines as Potential Anticancer Agents.

The continuous need for new anticancer drugs is never-ending task due to cancer resistance to the existing drugs. This article aimed to design, synthesis, characterization, and anticancer evaluation of cyanopyridines, pyridopyrazolopyrimidines and pyridopyrazolotriazines. Anticancer activity of the synthesized compounds was determined using MTT assay against three cancer cell lines, namely liver cancer cell line (HepG-2), pancreatic cancer cell line (PANC-1), non-small lung cancer cell line (A-549) and normal fibroblast. A series of 3-cyanopyridines (2a,b, 4, 5, 9), pyridopyrimidine (10), pyridopyrazolopyrimidines (11a-c, 12a,b, 18), pyrazolopyridine salt (13) and pyridopyrazolotriazines (16a,b) were synthesized from 3-cyano-4,6-dimethyl-2-pyridone. The synthesized compounds were evaluated in vitro for their anticancer activity and their chemical structures were determined by elemental analysis and spectroscopic data. Some of the synthesized compounds showed remarkable anticancer activities, especially 11a exhibited superior potency to the reference drug cisplatin against A-549 (IC50 = 9.24 μg mL-1 compared to 11.76 μg mL-1 for reference drug) and was found to be safe (IC50 = 66 μg mL-1) for normal fibroblast. Furthermore, compound 16a displayed the highest activity among the tested compounds against HepG-2 (IC50 = 6.45 μg mL-1 equipotent to cisplatin) with the highest safety profile for normal fibroblast (IC50=113.97 μg mL-1).

Glypican-3-Targeted Alpha Particle Therapy for Hepatocellular Carcinoma.

Glypican-3 (GPC3) is expressed in 75% of hepatocellular carcinoma (HCC), but not normal liver, making it a promising HCC therapeutic target. GC33 is a full-length humanized monoclonal IgG1 specific to GPC3 that can localize to HCC in vivo. GC33 alone failed to demonstrate therapeutic efficacy when evaluated in patients with HCC; however, we posit that cytotoxic functionalization of the antibody with therapeutic radionuclides, may be warranted. Alpha particles, which are emitted by radioisotopes such as Actinium-225 (Ac-225) exhibit high linear energy transfer and short pathlength that, when targeted to tumors, can effectively kill cancer and limit bystander cytotoxicity. Macropa, an 18-member heterocyclic crown ether, can stably chelate Ac-225 at room temperature. Here, we synthesized and evaluated the efficacy of [225Ac]Ac–Macropa–GC33 in mice engrafted with the GPC3-expressing human liver cancer cell line HepG2. Following a pilot dose-finding study, mice (n = 10 per group) were treated with (1) PBS, (2) mass-equivalent unmodified GC33, (3) 18.5 kBq [225Ac]Ac–Macropa–IgG1 (isotype control), (4) 9.25 kBq [225Ac]Ac–Macropa–GC33, and (5) 18.5 kBq [225Ac]Ac–Macropa–GC33. While significant toxicity was observed in all groups receiving radioconjugates, the 9.25 kBq [225Ac]Ac–Macropa–GC33 group demonstrated a modest survival advantage compared to PBS (p = 0.0012) and 18.5 kBq [225Ac]Ac–IgG1 (p = 0.0412). Hematological analysis demonstrated a marked, rapid reduction in white blood cells in all radioconjugate-treated groups compared to the PBS and unmodified GC33 control groups. Our studies highlight a significant disadvantage of using directly-labeled biomolecules with long blood circulation times for TAT. Strategies to mitigate such treatment toxicity include dose fractionation, pretargeting, and using smaller targeting ligands.

Experimental Application of High-content Screening in Evaluating the Induction of Cell-cycle Arrest and Apoptosis on Human Liver Cancer Cell Line Hep-G2

This study discusses the results of the experimental application of high-content screening (HCS) techniques in evaluating the induction of cell-cycle arrest and apoptosis on human liver cancer cell line, Hep-G2. Accordingly, the bisbenzimide-stained cells (Hoechst 33342; 350 to 500 nM) were analyzed by using an Olympus scanˆR HCS-system to determine the cell-cycle phases (G1, S, and G2/M) and apoptosis as well. As a result, the cell-cycle arrest could be indicated by an increase in G2/M population of Hep-G2 cells after 24h exposure to zerumbone (Zer4; 9 µg/mL) and a similar observation could be made for paclitaxel (Pac; 4 µg/mL) as a reference substance.&#x0D; Keywords&#x0D; Apoptosis, cell-cycle arrest, high-content screening, human liver cancer cell line Hep-G2.&#x0D; References&#x0D; [1] D. Hanahan, R.A. Weinberg, Hallmarks of cancer: the next generation, Cell 144 (2011) 646–674.[2] M. Malumbres, M. Barbacid, Cell cycle, CDKs and cancer: a changing paradigm, Nat. Rev. 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Gerasimaitė, The use of Hoechst dyes for DNA staining and beyond, Chemosensor 6 (2018) 1-18.[21] V. Kumar, A.K. Abbas, J.C. Aster, Robbins and Cotran Pathologic Basis of Disease, Ninth ed., Elsevier/Saunders, Philadelphia (2015).[22] N.A. Jensen et al., Establishment of a high content assay for the identification and characterisation of bioactivities in crude bacterial extracts that interfere with the eukaryotic cell cycle, J. Biotechnol 140 (2009) 124-134.[23] H.S. Rahman, et al., Zerumbone induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in Jurkat cell line, Nat. Prod. Commun 9 (2014) 1237-1242.[24] S.I. Abdelwahab, et al., Zerumbone inhibits interleukin-6 and induces apoptosis and cell cycle arrest in ovarian and cervical cancer cells, Intern. Immunopharm 12 (2012) 594-602.[25] M. 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Determination of structure and anticancer activity of MM2 compound, isolated from endophytic fungus Aspergillus terreus-RTN3 of Alpinia chinensis Rosc.

The study has isolated endogenous A. terreus-RTN3 strain from young stems of Alpinia chinensis Rosc.-Zingiberaceae family. Cultivating and extracting compounds containing metabolites that are resistant to Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus (MRSA). Determining the number of antibacterial compounds in the crude extract by thin-layer chromatography and vacuum liquid chromatography (VLC), the research has isolated pure MM2 compound with high antioxidant activity and spectral resolution to find the structure compound MM2 (Methyl 2-((4-amino-2-bromo-3-methyl-5-thioxocyclopenta-1,3-dien-1-yl) oxygen) -4-hydroxy-6-methoxybenzoate). This is a new compound that has not been announced in any works in the world. MM2 compound has a high antioxidant activity, the ability to catch α, α-diphenyl-β-picrylhydrazyl (DPPH) free radicals increases linearly by concentration, at concentration 400ppm of MM2 is capable of catching over 75% of DPPH free radicals. The MM2 compound also has the ability to inhibit 4 test cell lines: breast cancer (MCF-7), cervical cancer (Hela), liver cancer (Hep G2) and lung cancer (NCI-H460). The results showed that MM2 compound’s ability to inhibit cancer cell lines increased linearly, at concentrations of 100 µg/ml of MM2 compound, which inhibited nearly 80% of cancer cell lines and was high most in liver cancer cell line HepG2 (at a concentration of 100 µg/ml inhibits 86.82% of liver cancer cells HepG2).

Bioactive Small Molecules Having a Fatty Residue. Part VI: Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies of New Pyrimidine Derivatives as Antitumor Agents

Difficultly accessible pyrimidine, thiazolopyrimidine, triazolopyrimidine, and thiazinopyrimidine derivatives containing an oleyl residue were synthesized via alkylation of 6-oleyl-2-thiouracil. The structure of the synthesized compounds was established on the basis of their spectral data, elemental analyses, and chemical behavior. The in vitro cytotoxicity of selected compounds was screened against two human cancer cell lines, MCF-7 breast cancer and HepG2 liver cancer cell lines. 8-[(8Z)-Heptadec-8-en-1-yl)-3-hydroxy-3,4-dihydropyrimido[2,1-b][1,3]thiazin-6(2H)-one turned out to be the most potent with IC50 values of 12.5 and 20 μg/mL against MCF-7 and HepG2 cancer cell lines, respectively. The structure–activity relationship for this compound was interpreted in terms of molecular docking and molecular dynamics studies.

Effects of matrine in combination with cisplatin on liver cancer.

Matrine, an alkaloid isolated from Sophora flavescens, promotes tumor cell apoptosis and strengthens the anticancer capacity of chemotherapeutic drugs. The present study aimed to investigate the inhibitory effect and underlying mechanism of matrine in combination with cisplatin on liver cancer progression. Tumor progression was studied in nude mice. The human liver cancer cell line HepG2 was injected into BALB/c nude mice subcutaneously to establish a tumor model. Mice were subsequently treated with matrine, cisplatin, matrine + cisplatin or normal saline. Nude mice and tumor growth were monitored. Tumors were excised and the expression of survivin, caspase-3, caspase-7 and caspase-9 was detected by immunohistochemistry. Western blotting was used to determine the expression of survivin, caspase-3, caspase-7, caspase-9 and X-linked inhibitor of apoptosis protein (XIAP) in tumor tissues. The results demonstrated that matrine exerted anticancer effects in liver cancer-transplanted tumors, as evidenced by decrease in tumor weight and volume. Furthermore, the tumor inhibition rate in mice treated with matrine + cisplatin was 83.3%, whereas it was of 37.5 and 75% in mice treated with matrine or cisplatin alone, respectively. In addition, the expression of survivin and XIAP was significantly downregulated, whereas the expression of caspase-3, caspase-7 and caspase-9 was significantly upregulated in tumor tissues from nude mice treated with matrine + cisplatin, compared with those treated with cisplatin, matrine or normal saline. These findings suggested that the combination of matrine and cisplatin may promote tumor cell apoptosis in liver cancer by activating the caspase apoptosis pathway and suppressing the survivin-associated inhibition of caspase-9.

Novel Pt-Ag3PO4/CdS/Chitosan Nanocomposite with Enhanced Photocatalytic and Biological Activities.

Decorating photocatalysts with noble metal nanoparticles (e.g., Pt) often increases the catalysts’ photocatalytic activity and biomedical properties. Here, a simple and inexpensive method has been developed to prepare a Pt-Ag3PO4/CdS/chitosan composite, which was characterized and used for the visible light-induced photocatalytic and antibacterial studies. This synthesized composite showed superior photocatalytic activity for methylene blue degradation as a hazardous pollutant (the maximum dye degradation was observed in 90 min of treatment) and killing of Gram positive bacterial (Staphylococcus aureus and Bacillus cereus) as well as Gram negative bacteria (Klebsiella pneumoniae, Salmonella typhimurium, Escherichia coli, and Pseudomonas aeruginosa) under visible light irradiation. The antibacterial activity of CdS, CdS/Ag3PO4, and Pt-Ag3PO4/CdS/chitosan against E. coli, Pseudomonas aeruginosa, Salmonella typhimurium, Klebsiella pneumoniae, Staphylococcus aureus, and Bacillus cereus showed the zone of inhibition (mm) under visible light and under dark conditions at a concentration of 20 µg mL−1. Furthermore, the cell viability of the CdS/chitosan, Ag3PO4, Ag3PO4/CdS/chitosan, and Pt-Ag3PO4/CdS/chitosan were investigated on the human embryonic kidney 293 cells (HEK-293), Henrietta Lacks (HeLa), human liver cancer cell line (HepG2), and pheochromocytoma (PC12) cell lines. In addition, the results indicated that the photodegradation rate for Pt-Ag3PO4/CdS/chitosan is 3.53 times higher than that of CdS and 1.73 times higher than that of the CdS/Ag3PO4 composite. Moreover, Pt-Ag3PO4/CdS/chitosan with an optimal amount of CdS killed large areas of different bacteria and different cells separately in a shorter time period under visible-light irradiation, which shows significantly higher efficiency than pure CdS and other CdS/Ag3PO4 composites. The superb performances of this composite are attributed to its privileged properties, such as retarded recombination of photoinduced electron/hole pairs and a large specific surface area, making Pt-Ag3PO4/CdS/chitosan a valuable composite that can be deployed for a range of important applications, such as visible light-induced photocatalysis and antibacterial activity.

Anti-oxidant and Antiproliferative Activities of Mongolian Medicinal Plant Extracts and Structure Isolation of Gnetin-H Compound.

Reactive oxygen species are involved in the etiology and progress of many kinds of diseases such as cancer, cardiovascular diseases, inflammatory and neurodegenerative disorders. Epidemiological studies reported that fruits, vegetables, and wines containing a high percentage of phenolics and flavonoids showed a positive impact in treating inflammatory diseases, reducing cancer risk, and increasing life expectancy. Some Mongolian medicinal plants were studied for their antioxidant activity and anticancer effects. Selected Mongolian medicinal plant extracts were examined for their antioxidant activity by the DPPH-radical scavenging assay, the content of phenolics and flavonoids by Folin-Ciocalteu and the Dowd method, respectively, and anti-cancer activities in human hepatoma cell line HepG2 cells by MTT assay. Methanol extract from Hippophae rhamnoides L. leaf and ethanol extract from Artemisia macrocephala Jacq. ex Bess. showed the highest efficiency to scavenge free radicals. Ethanol extracts from Hippophae rhamnoides L. grain and Paeonio anomala L. leaf showed the highest total phenolics content, whereas Hippophae rhamnoides L. fruit methanol extract and ethanol extract from Caragana leucophloea pojark. mentioned the highest flavonoids content. The Artemisia macrocephala Jacq. ex Bess seed wallet and Paeonia anomala L. seed wallet showed the most potent antiproliferative effects against human liver cancer HepG2 cell line. Gnetin-H compound was isolated from the Paeonio anomala L. seed wallet extract, and its molecular structure was determined by 1H and 13C NMR spectrum and IR spectroscopy methods. The screening study on anti-oxidative effects of 21 extracts from 15 Mongolian medicinal plants showed anti-oxidative activities and was rich in phenolics and flavonoids. Among these, methanol extract of the Hippophae rhamnoides L. leaf showed a better anti-oxidative effect than the ethanol extract. Artemisia macrocephala Jacq. ex Bess and Paeonia anomala L. seed wallet mentioned the best anti-cancer effects. Gnetin-H, methyl gallate, ethylgallate were the major components in the extract from the Paeonio anomala L. seed wallet. Finally, the molecular structure of gnetin-H was determined by NMR and IR spectroscopy. Further investigation, especially in vivo antioxidant activity, is needed to justify the use of a natural source of antioxidants to prevent the progression of diseases such as cancer.

Unexpected structure of enaminone Pd(II) complex in comparison with Cu(II) complex: Synthesis, characterization, DNA binding and antitumor activity

Novel Pd(II) and Cu(II) complexes have been synthesized by the reaction of Na2PdCl4 and CuCl2·2H2O with fluorinated enaminone ligand leading to the formation of complexes having the formulae [Pd(enm)Cl2] and [Cu2(diCO)4]; where enm and diCO are enaminone and deprotonated dicarbonyl containing ligands, respectively. The structures and geometry of the two metal chelates have been elucidated by applying alternative spectral and analytical tools including elemental analysis, FT-IR spectra, 1H NMR spectra and UV–Vis spectra. The molecular structure of the Cu(II) complex has been determined by single crystal X-ray diffraction; the complex crystalizes in monoclinic P21/c space group. Square pyramidal geometry has been confirmed for Cu(II) complex where Pd(II) complex has the expected square planar geometry. The mechanism of the in-situ conversion of the enaminone to dicarbonyl ligand with CuCl2·2H2O was illustrated. The type of interaction between the two complexes and salmon sperm DNA (SS-DNA) has been studied applying absorption spectra and viscosity measurements. The binding constant values (kb) was calculated to be (1.17 ± 0.6) × 104 and (3.62 ± 0.4) × 104 M−1 for Pd(enm)Cl2 and Cu2(diCO)4, respectively, which confirmed the interaction of the two complexes with DNA via intercalative mode of interaction. Intercalative binding mode between the studied compounds and DNA was further confirmed by the results of viscosity measurements. The anticancer activity of the two metal complexes has been evaluated against breast cancer cell line (MCF-7) and the liver cancer cell line (HepG-2) in comparison with the well-known anticancer drug cis-DDP. Surprisingly, we found that Cu2(diCO)4 complex has activity (IC50 = 3.26 μg/mL) against a human liver cancer cell line (HepG2) exceeding the efficiency of the reference drug cis-DDP (IC50 = 3.67 μg/mL).

Design and anti-tumor evaluation of new platinum(II) and copper(II) complexes of nitrogen compounds containing selenium moieties

Three ligands containing selenium were synthesized by refluxing 3-acetylcoumarin (AC), 3-acetylbenzocoumarin (ABC) and acetobenzylsulfonamide (ABS) with selenosemicarbazide. The synthesized ligands were reacted with two metal salts namely; copper(II) nitrate and potassium teterachloroplatinate(II). The obtained copper and platinium complexes were characterized by different spectroscopic techniques including, 1H NMR, 13C NMR, IR, UV–visible, ESR and MS. The biological activity of newly synthesized compounds were evaluated using different testes like in-vitro antimicrobial screening, anticancer, glutathione-S-transferase and Catalase activities. The in-vitro cytotoxicity against human breast cancer cell line (MCF-7), human liver cancer cell line (HepG-2) and human colon cancer cell line (HCT-116) and Human normal melanocytes (HFB 4) was investigated, where some of the tested compounds were equipotent, while the others were more potent compared with 5-flurouracil and cis-platin as reference drugs. The obtanined results showed that the best results were for copper(II) complexes and especially for benzocoumarin ligand.

Synthesis of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Cytotoxic Candidates

AbstractOstruthin, isolated from Paramignya trimera, was used as a scaffold to design its alkyl triphenylphosphonium derivatives. With the optimal reaction conditions in hand, five alkyl triphenylphosphonium ostruthin derivatives (1–5) were synthesized. Ostruthin and its derivatives were tested for cytotoxicity against human PANC‐1 pancreatic, Hela cervical, and HepG2 liver cancer cell lines. Ostruthin and its hexyl and heptyl triphenylphosphonium derivatives (4 and 5) showed strong preferential cytotoxicity against PANC‐1 cells with the PC50 values of 10.3 and 14.4 μM, respectively. In addition, compounds 4 and 5 also exhibited potent cytotoxicity towards HeLa cells with the IC50 values of 24.8 and 18.5 μM, respectively. The hexyl triphenylphosphonium group in 4 was found to slightly enhance cytotoxicity against HepG2 cells. Further, the morphological changes and the live‐cell imaging result suggested the anticancer potential against HeLa cells of the synthesized ostruthin derivative 5.