Cell Growth Inhibitory Effects Research Articles

The effect of organic solvents on selected microorganisms and model liposome membrane

The effect of methanol, ethanol, acetone, N,N-dimethylformamide (DMF), dimethyl sulfoxide and Nujol on the growth of Escherichia coli DH5α, Bacillus subtilis and Saccharomyces cerevisiae D273 was investigated. All of the tested cultures appeared susceptible to the organic media they were treated with, which evinced in apparent hindering of cell development. The observed diverse solvent tolerance, except from their different biochemical activity, may also be related to the changes in cell membrane fluidity induced by the solvent species. Parallel electron paramagnetic resonance investigations using egg yolk lecithin model liposomes revealed that the fluidity of the phospholipid system in cell membranes may either be considerably decreased (Nujol, DMF, ethanol) or increased (acetone), thus rendering difficult the intracellular nutrient supply. Hence, even the chemically neutral Nujol produced a distinct cell-growth inhibitory effect. These results are fairly consistent with the outcome of the survival tests, particularly for the bacteria strains.

Synergistic effect of co-treatment with all-trans retinoic acid and 9-cis retinoic acid on human lung cancer cell line at molecular level.

The major challenge in treating cancers with ATRA is the limited availability inside the cell and resistance developed in prolonged treatment. We made an attempt for co-treatment of human NSCLC cell lines (A549) with ATRA and its isomeric precursor (9cisRA). In this study, the growth inhibitory effect of ATRA, 9cisRA and combination of both were tested in A549 cells by MTT and Trypan blue assays. As the effects of retinoid are mediated through their receptors, their gene expression levels were analyzed by RT-PCR. The target gene receptor, RAR-β protein expression, was analyzed by immunocytochemistry. The cancer cell (A549) growth inhibitory effect was significantly (p ≤ 0.001) enhanced in combination treatment when compared with the result of individual treatments. The mRNA expression levels of both RAR-β and RXR-β were found to be increased in co-treatment (band density of 0.75 and 0.806, respectively) when compared with 9cisRA treatment (0.25 and 0.112) and ATRA treatment (0.01 and 0.081). A concomitant enhancement in the target RAR-β protein expression was observed in co-treated cells when compared with individual treatments. We thus conclude that the co-treatment had increased the availability of ATRA, by isomerization of the 9cisRA which then resulted in an increased expression of both RAR-β and RXR-β receptors and the target protein RAR-β which in turn inhibited lung cancer cell growth. Our study results have explored the mechanism of synergistic effect of co-treatment with ATRA and 9cisRA and further preclinical studies are necessary to validate the application of co-treatment of retinoid in clinical use.

The effects of HSP27 against UVB-induced photoaging in rat skin

Skin photoaging refers to the phenomenon of skin aging or accelerated aging as a result of long-term UV exposure. Ultraviolet radiation can lead to DNA damage, cell apoptosis, cell growth inhibition and carcinogenic effects. Evidence suggests that hsp27 can protect cells from apoptosis induced by various stimuli in vivo and in vitro. However, modulation in hsp27 expression toward skin protection against UVB treatment has not been investigated clearly. In this study, we aimed to investigate the effects of hsp27 against UVB-induced photoaging in rat skin and to explore the underlying mechanisms. In the present study, we identified that the level of hsp27 increased after UVB irradiation induced chronic photoaging rat model. In order to investigate the function of hsp27 in UVB-induced skin photoaging, we used adeno-associated virus (AAV) to specificity reduce the expression of hsp27 in rat skin. In contrast to UVB group, we found that collagen fibers were disorganized and elastic fibers were thickened and twisted in UVB-AAV group. In the UVB-AAV group, reduced hsp27 enhanced the oxidative stress. Aging markers (SA-β-Gal staining and the protein levels of p16, p53, p21) were significantly changed in the hsp27 decreased group. However, in hsp27 deletion group, the expression of antiapoptotic factor bcl-2 was decreased, while the apoptosis factor bax was increased after UVB irradiation. These findings suggested that hsp27 was involved in oxidative stress, aging and apoptosis of skin after UV exposure. Management the expression of hsp27 can be used as a potential intervention method to alleviate UVB-induced skin damage.

Abstract P2-06-05: TP-0903, an AXL kinase inhibitor, reduces inflammatory breast cancer aggressiveness and macrophage polarization through additional mechanisms that may include JAK2 and Aurora B

Abstract Background: Inflammatory breast cancer (IBC) is the most lethal and aggressive type of breast cancer; it accounts for 2-4% of breast cancer cases but causes 8-10% of breast cancer deaths. Novel targeted therapy to improve the outcomes of patients with IBC is urgently needed. The receptor tyrosine kinase AXL is a driver for metastasis and drug resistance in various cancers, including breast cancer. Our previous work showed that AXL signaling contributes to the aggressiveness of IBC. In addition, emerging evidence indicates that the tumor microenvironment components, particularly tumor-associated macrophages, are critical drivers of the IBC clinical phenotype and promote IBC metastasis. AXL signaling has been shown to modulate the tumor microenvironment. In the present study, we investigated the impact of TP-0903, a small-molecule AXL kinase inhibitor, with additional activity against Aurora B and Janus kinase 2 (JAK2), on IBC cells and macrophage polarization. Methods: The effects of TP-0903 on IBC cell proliferation, migration/invasion, and mammosphere formation were analyzed. The effects of TP-0903 on the polarization of human monocytic cells THP-1 were tested in vitro. In addition, the signaling pathways involved in TP-0903-regulated M2 macrophage polarization were investigated using Western blotting. Results: The half-maximal inhibitory concentration (IC50) of TP-0903 in an array of IBC cells (including SUM149, SUM190, BCX010, FC-IBC-02, MDA-IBC-3, and KPL4) ranged from 66 nM to 346 nM, suggesting a strong cell growth inhibitory effect. TP-0903 treatment decreased the migration, invasion, and mammosphere formation of IBC cells. In addition, TP-0903 inhibited both AXL signaling and Aurora B activation, which induced a G2/M cell cycle arrest in IBC cells. Based on the importance of AXL and JAK2 in the regulation of the tumor microenvironment, we showed that TP-0903 decreased expression of CD163/CD206 and the CCL17/CCL18 cytokine, and markers of M2 macrophages, suggesting that TP-0903 treatment inhibits the polarization of THP-1 cells to M2 macrophages in vitro. We also found that TP-0903 treatment decreased the phosphorylation of STAT6, a critical molecule in M2 polarization, and that knockdown of STAT6 expression decreased M2 macrophage polarization, indicating that TP-0903 may regulate macrophage polarization via STAT6 signaling. Conclusion: Our results demonstrated the dual functions of TP-0903 targeting of both IBC cells and macrophages, possibly via the targeting of multiple kinases, including AXL and Aurora B. Examinations of the impact of TP-0903 on the cross-talk between IBC cells and macrophages in vitro and in vivo and the related mechanisms are ongoing and will be presented at the meeting. Citation Format: Cheng Y, Funakoshi Y, Wang X, Warner SL, Bearss DJ, Ueno NT. TP-0903, an AXL kinase inhibitor, reduces inflammatory breast cancer aggressiveness and macrophage polarization through additional mechanisms that may include JAK2 and Aurora B [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-05.

Identification of Further Components of an Anticancer Defense System Composed of Small Molecules Present in the Serum.

Earlier we assumed that small molecules selectively accumulated in cancer cells might have a role in a defense system capable of killing cancer cells. We reported earlier that an experimentally selected mixture of substances present in the serum ("active mixture," AM) shows a selective toxic effect in vitro and in vivo on various cancer cells. In this study we investigated additional compounds found in the serum to further expand our knowledge of this defense system. The cell proliferation was detected by WST-1 assay. The mRNA level of the examined genes was measured by quantitative real-time polymerase chain reaction. We identified 34 additional compounds (l-amino acid metabolites, phenolic acids, d-amino acids, keto acids, etc.), which when applied in a per se nontoxic concentration are able to enhance the effect of AM. The combination of the mixture of these newly identified substances (new mixture, NM) with AM produced a significantly higher cancer cell growth inhibitory effect than NM or AM applied alone on HeLa, MCF-7, PC-3, Caco-2, HepG2, and 4T1 cancer cell lines, and more efficiently induced the expression of certain proapoptotic genes in HeLa cells. Any given combinations of the individual compounds of AM and NM always produced an increased effect compared with AM alone. The newly identified compounds significantly enhance the anticancer effect of AM. The components of AM and NM together may form part of a defense system capable of killing cancer cells and are worthy of further investigation.

ETS1 targets RYBP transcription to inhibit tumor cell proliferation

ETS1 (E26 transformation specific-1) is the founding member of ETS transcriptional factor family. It transcriptionally modulates numerous gene expressions, and is involved in cellular differentiation, tissue remodeling, angiogenesis, drug resistance and tumorigenesis. ETS1 is usually regarded as an oncogene. However, its apoptosis-inducing activity was also frequently reported. Here, we identified RYBP (Ring1 and YY1 binding protein), a critical epigenetic regulator and apoptosis enhancer, as a novel transcriptional target of ETS1. Specifically, we found that overexpression of ETS1 up-regulates the promoter activity of RYBP in HEK293T and tumor cells from different tissue origins, indicating a universal transcriptional regulatory effect. Subsequently, both overexpression and RNA interfering experiments demonstrated that ETS1 positively modulates RYBP expression from both mRNA and protein levels. Bioinformatics analysis combined with site-directed mutagenesis suggested that there probably exist a multiple of ETS1 binding sites in RYBP promoter region, and chromatin immunoprecipitation assay validates the physical association between ETS1 protein and RYBP promoter region. Functional studies showed that ectopic expression of ETS1 significantly suppresses tumor cell proliferation. However, this inhibitory effect was partially compromised when RYBP was concomitantly knocked down by its specific short hairpin RNA. Meanwhile, we provide evidence to demonstrate that cyclin-dependent kinase inhibitor p21 is possibly involved in this regulatory loop. Taken together, our current study identified RYBP as a new transcriptional target which is utilized by ETS1 to carry out its tumor cell growth inhibitory effect.

New spirobisnaphthalenes from an endolichenic fungus strain CGMCC 3.15192 and their anticancer effects through the P53-P21 pathway.

Natural products from fungi have remained a rich resource for drug discovery. Here we report the isolation of three new spirobisnaphthalenes, namely sacrosomycin A-C (1–3), and three known analogues (4–6), from the ethyl acetate extract of a nonsporulating endolichenic fungus derived from Peltigera elisabethae var. mauritzii. The structures of these compounds were elucidated by IR, UV, MS, and NMR. Biological functions of these compounds were evaluated using cultured human cancer cell lines. Short-term cell growth and long-term cell survival assays show that compound 5 demonstrated the strongest cancer cell growth inhibition effect. We reveal that compound 5 induced both cell cycle arrest at the G2/M phase and cell death. Using western blotting, luciferase reporter assay and quantitative PCR (qPCR), we show that compound 5 induced up-regulation of the P53–P21 pathway, supporting the cell cycle arrest and growth inhibition effect of this compound. In contrast, these compounds did not induce cell death in a normal cell line. These results demonstrate a potential anticancer effect of this rare family of spirobisnaphthalene compounds isolated from endolichenic fungi.

Anticancer activity of britannin through the downregulation of cyclin D1 and CDK4 in human breast cancer cells.

Both apoptotic induction and cell cycle blockade in cancer cells are effective strategies to eliminate cancer cells. Many conventional cancer drugs that induce apoptosis and inhibit cell cycle progression have been reported as potential therapeutics for various types of cancer. Britannin is a natural sesquiterpene lactone that its profound anticancer properties were revealed in our previous study. In this study, we evaluated the effects of britannin on the cell cycle distribution and also cell cycle-related proteins. Analysis of cell cycle distribution was carried out using flow cytometer. The effects of britannin on cyclin D1 and CDK4 expression were evaluated using the Western blot. The obtained results show that britannin at the low concentrations induces cell growth inhibition mainly through G1-phase arrest while it seems that apoptosis contributes to cell growth inhibitory effect of high doses of britannin. Reduction of cyclin D1 and CDK4 protein levels were also observed after treating cancer cells with britannin. The obtained results reveal that britannin can inhibit MCF-7 and MDA-MB-468 breast cancer cells proliferation through arresting cell cycle progression through cyclin D1/CDK4-mediated pathway.

Juglone Induces Michigan Cancer Foundation-7 Human Breast Cancer Cells Apoptosis through Bcl-2-Associated X protein/B-cell lymphoma/leukemia-2 Signal Way

Pharmacognosy Magazine ,2019,15,65,573-578.DOI:10.4103/pm.pm_604_18Published:September 2019Type:Original Article Authors:Qing Luo, Kang Hu, Fang Chen, Feng-Jiao Gan, Yuan-Xiu Leng, Xu-Mei Chen, and Su-Hong Sun Author(s) affiliations:Qing Luo1, Kang Hu2, Fang Chen1, Feng-Jiao Gan2, Yuan-Xiu Leng1, Xu-Mei Chen1, Su-Hong Sun2 1Department of Oncology Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi, China 2Breast and Thyroid Disease Medical Center, Affiliated Hospital of Zunyi Medical University, Zunyi, China Abstract:Background: Juglone is a natural pigment, which has a cytotoxic effect against tumor cells. However, its cytotoxicity to human breast cancer cells (Michigan Cancer Foundation-7 [MCF7]) has not been demonstrated. Objective: The objective was to observe the effect of Juglone on the protein expression of caspase-3, 9 in the apoptosis of Human Breast Cancer Cells (MCF7) and apoptosis-related protein, Bcl-2-associated X protein (Bax), and B-cell lymphoma-2 (Bcl-2) and investigate in the inhibitory effect of MCF7. Materials and Methods: Methyl thiazolyl tetrazolium experiment was performed for the detection of the cell growth inhibition effect of MCF7. The apoptosis rate was detected by flow cytometry. Western Blot was used to detect the protein expression of Bax, Bcl-2, and caspase. The messenger RNA (mRNA) was tested using quantitative real-time polymerase chain reaction. Results: Juglone inhibited the growth of MCF7 cells in a concentration- and time-dependent manner and promotes the apoptosis of MCF7 cells in a concentration-dependent manner. Compared with control group, the Juglone group raised the expression of Bax protein (*P < 0.05), and the protein expression of Bcl-2 was decreased (*P < 0.05). The expression of caspase-3 protein was not changed, and the caspase-9 was significantly elevated in the high concentration of Juglone. Cleaved caspase-3, -9 protein was significantly raised (*P < 0.05). The mRNA levels of Bax, caspase-3, and caspase-9 in MCF7 cells of Juglone group were significantly increased compared with control, while the expression of Bcl-2 was suppressed obviously. Conclusion: Juglone inhibited the growth of MCF7 cells and promotes the apoptosis of MCF7 cells. Its mechanism in promoting MCF7 cell apoptosis may be related to the decrease of the expression of the mitochondrial pathway-associated apoptosis factor Bcl-2, increase of the protein expression of Bax, and mitochondrial pathway downstream caspase-3, 9. Keywords:Apoptosis, B-cell lymphoma/leukemia-2, Bcl-2-associated X protein, Juglone, Michigan Cancer Foundation-7View:PDF (1.86 MB)

Polymeric micelles loading with ursolic acid enhancing anti-tumor effect on hepatocellular carcinoma.

Ursolic acid (UA) is widely found in many dietary plants, which has been proved to be effective in cancer therapy. But unfortunately its hydrophobic property limits its clinical application. Polymer micelles (PMs) are constructed from amphiphilic block copolymers that tend to self-assemble and form the unique core-shell structure consisting of a hydrophilic corona outside and a hydrophobic inner core. PMs could entrap the hydrophobic substance into its hydrophobic inner core for solubilizing these poorly water-soluble drugs and it is widely applied as a novel nano-sized drug delivery system. This study aimed to develop the drug delivery system of UA-loaded polymer micelles (UA-PMs) to overcome the disadvantages of UA in clinical application thus enhancing antitumor effect on hepatocellular carcinoma. UA-PMs was prepared and characterized for the physicochemical properties. It was investigated the cell-growth inhibition effect of UA-PMs against the human hepatocellular carcinoma cell line HepG2 and human normal liver cell line L-02. UA-PMs was evaluated about the in vivo toxicity and the antitumor activity. We took a diblock copolymer of methoxy poly (ethylene glycol)-poly(L-lactic acid) (mPEG-PLA) as carrier material to prepare UA-PMs by the thin-film dispersion method. MTT assay and wound-healing assay were investigated to assess the inhibition effect of UA-PMs against HepG2 cells on cell-growth and cell-migration. Further, we chose KM mice for the acute toxicity experiment and assessed the antitumor effect of UA-PMs on the H22 tumor xenograft. UA-PMs could markedly inhibit the proliferation and migration of HepG2 cells. In vivo study showed that UA-PMs could significantly inhibit the growth of H22 xenograft and prolong the survival time of tumor-bearing mice. It demonstrated that UA-PMs possess great potential in liver cancer therapy and may enlarge the application of UA in clinical therapy.

Inhibitory Effect of Synthetic Flavone Derivatives on Pan-Aurora Kinases: Induction of G2/M Cell-Cycle Arrest and Apoptosis in HCT116 Human Colon Cancer Cells.

Members of the aurora kinase family are Ser/Thr kinases involved in regulating mitosis. Multiple promising clinical trials to target aurora kinases are in development. To discover flavones showing growth inhibitory effects on cancer cells, 36 flavone derivatives were prepared, and their cytotoxicity was measured using a long-term clonogenic survival assay. Their half-maximal growth inhibitory effects against HCT116 human colon cancer cells were observed at the sub-micromolar level. Pharmacophores were derived based on three-dimensional quantitative structure–activity calculations. Because plant-derived flavones inhibit aurora kinase B, we selected 5-methoxy-2-(2-methoxynaphthalen-1-yl)-4H-chromen-4-one (derivative 31), which showed the best half-maximal cell growth inhibitory effect, and tested whether it can inhibit aurora kinases in HCT116 colon cancer cells. We found that derivative 31 inhibited the phosphorylation of aurora kinases A, aurora kinases B and aurora kinases C, suggesting that derivative 31 is a potential pan-aurora kinase inhibitor. The results of our analysis of the binding modes between derivative 31 and aurora A and aurora B kinases using in-silico docking were consistent with the pharmacophores proposed in this study.

Antineoplastic Properties of Phyto-synthesized Silver Nanoparticles from Hibiscus Sabdariffa Linn. Bark Extract

Objectives: In recent years, green synthesis of silver nanoparticles (AgNPs) has gained much interest from researchers as biomedical treatments. The purpose of this study was to determine if AgNPs synthesized from Hibiscus Sabdariffa L. bark extract are an effective stabilizing agent and inhibit Ehrlich ascites carcinoma (EAC) cell growth. Methods: AgNPs were prepared by the reaction of 0.6mM silver nitrate and 5% bark extract. Synthesis of AgNPs were confirmed by UV-visible spectroscopy as well as characterized by scanning electron microscopy, x-ray diffraction, and fourier transform infrared spectroscopy. AgNPs was applied on 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) experiments to determine its antioxidant activity as well as its cytotoxic effect against EAC cells. In vivo, the antineoplastic effect of AgNPs was tested against EAC cells. Results: The synthesized AgNPs have a surface plasmon resonance band centered at 475 nm. Fourier transform infrared spectroscopy (FTIR) spectra showed major peaks of phytochemicals and proteins involved in AgNPs biosynthesis by identifying different functional groups involved in effective capping of AgNPs. The scanning electron microscope (SEM) analysis of AgNPs showed spherical nanoparticles with mean size 90.82 nm. The DPPH and ABTS assays revealed the antioxidant activity of AgNPs with IC50 31.74±2.06 and 15.45±2.72 μg/ml that was comparable to catechin. The synthesized AgNPs exhibited effective cytotoxic activity against EAC cells and the inhibitory concentration (IC50) was recorded at 32.00 µg/ml. AgNPs showed effective cell growth inhibition, increased life span, reduced tumor weight, restored all hematological characteristics to normal level and also induced apoptosis of EAC cells. Conclusion: This study proves that the phyto-synthesized AgNPs show effective anticancer properties against EAC cells.

익모초 추출물의 항산화 효과 및 MCF-7 유방암 세포주의 성장억제 유도에 관한 연구

익모초 추출물의 항산화 효과 및 MCF-7 유방암 세포주의 성장억제 유도에 관한 연구

New Pim-1 Kinase Inhibitor From the Co-culture of Two Sponge-Associated Actinomycetes.

Saccharomonospora sp. UR22 and Dietzia sp. UR66, two actinomycetes derived from the Red Sea sponge Callyspongia siphonella, were co-cultured and the induced metabolites were monitored by HPLC-DAD and TLC. Saccharomonosporine A (1), a novel brominated oxo-indole alkaloid, convolutamydine F (2) along with other three known induced metabolites (3-5) were isolated from the EtOAc extract of Saccharomonospora sp. UR22 and Dietzia sp. UR66 co-culture. Additionally, axenic culture of Saccharomonospora sp. UR22 led to isolation of six known microbial metabolites (6-11). A kinase inhibition assay results showed that compounds 1 and 3 were potent Pim-1 kinase inhibitors with an IC50 value of 0.3 ± 0.02 and 0.95 ± 0.01 μM, respectively. Docking studies revealed the binding mode of compounds 1 and 3 in the ATP pocket of Pim-1 kinase. Testing of compounds 1 and 3 displayed significant antiproliferative activity against the human colon adenocarcinoma HT-29, (IC50 3.6 and 3.7 μM, respectively) and the human promyelocytic leukemia HL-60, (IC50 2.8 and 4.2 μM, respectively). These results suggested that compounds 1 and 3 act as potential Pim-1 kinase inhibitors that mediate the tumor cell growth inhibitory effect. This study highlighted the co-cultivation approach as an effective strategy to increase the chemical diversity of the secondary metabolites hidden in the genomes of the marine actinomycetes.

Enhanced In Vitro Antitumor Activity of GnRH-III-Daunorubicin Bioconjugates Influenced by Sequence Modification.

Receptors for gonadotropin releasing hormone (GnRH) are highly expressed in various human cancers including breast, ovarian, endometrial, prostate and colorectal cancer. Ligands like human GnRH-I or the sea lamprey analogue GnRH-III represent a promising approach for the development of efficient drug delivery systems for targeted tumor therapy. Here, we report on the synthesis and cytostatic effect of 14 oxime bond-linked daunorubicin GnRH-III conjugates containing a variety of unnatural amino acids within the peptide sequence. All compounds demonstrated a reduced cell viability in vitro on estrogen receptor α (ERα) positive and ERα negative cancer cells. The best candidate revealed an increased cancer cell growth inhibitory effect compared to our lead-compound GnRH-III-[4Lys(Bu),8Lys(Dau=Aoa)]. Flow cytometry and fluorescence microscopy studies showed that the cellular uptake of the novel conjugate is substantially improved leading to an accelerated delivery of the drug to its site of action. However, the release of the active drug-metabolite by lysosomal enzymes was not negatively affected by amino acid substitution, while the compound provided a high stability in human blood plasma. Receptor binding studies were carried out to ensure a high binding affinity of the new compound for the GnRH-receptor. It was demonstrated that GnRH-III-[2ΔHis,3d-Tic,4Lys(Bu),8Lys(Dau=Aoa)] is a highly potent and promising anticancer drug delivery system for targeted tumor therapy.

Antioksidan ve antimiktobiyal özellikleri ile birlikte Craterellus cornucopioides (L.) Pers. türünün hücre büyümesi baskılama potansiyeli

Craterellus cornucopioides (L.) Pers which is also known as trumpet of death or horn of plenty, is a wild edible macrofungus. This study was conducted to elucidate the potential health beneficial properties of C. cornucopioides. Bioactive ingredients (phenolics, flavonoids, β-carotene and lycopene) and DPPH radical scavenging activities were determined. Additionally, cell growth inhibitory effects on HepG2 cells together with some bacteria were evaluated. Accordingly, water and methanol extracts contains 37.71±1.42 μg/mg and 13.78±1.60 μg/mg phenolic contents, respectively. Similarly, methanolic extracts have higher β-caroten and lycopene content as compared to aqueous extracts. In parallel with these antioxidants, methanolic extracts have also higher DPPH scavenging activity (IC50: 5.26±0.67 mg/ml). Besides, water extracts have higher flavonoid contents (2.13±0.06 μg/mg) then the methanolic extracts. C. cornucopioides has also an important cell growth inhibitory effects on HepG2 cell (IC50: 18.41±1.10 mg/ml for aqueous extracts and IC50: 3.14±1.07 mg/ml for methanolic extracts). Moreover, both extracts were effective on six different bacteria tested. As a result, this study indicates that C. cornucopioides could reduce the cellular oxidative stress because of its high antioxidant ingredients, inhibit the growth of pathogen microrganisms and have some degree of cell growth inhibitory potential at least to the HepG2 cells.Pers which is (L.) Craterellus cornucopioides

Phytosterol and γ-Oryzanol Conjugates: Synthesis and Evaluation of their Antioxidant, Antiproliferative, and Anticholesterol Activities.

Fifteen new multifunctional conjugates were designed and synthesized by chemically linking the steroidal framework of natural occurring γ-oryzanol and γ-oryzanol-derived phytosterols to a wide range of bioactive natural compounds (fatty acids, phenolic acids, amino acids, lipoic acid, retinoic acid, curcumin, and resveratrol). Starting from γ-oryzanol, which is the main component of rice bran oil, this study was aimed at assessing if the conjugation strategy might enhance some γ-oryzanol bioactivities. The antioxidant activity was evaluated through three different mechanisms, namely, DPPH-scavenging activity, metal-chelating activity, and β-carotene-bleaching inhibition. Measurement of the in vitro cell growth inhibitory effects on three different human cancer cellular lines was also carried out, and the potential hypocholesterolemic effect was studied. Compounds 10 and 15 displayed an improved antioxidant activity, with respect to that of γ-oryzanol. Compounds 2, 6, and 12 exerted an antiproliferative activity in the low micromolar range against HeLa and DAOY cells (GI50 < 10 μM). As for the claimed hypocholesterolemic effect of γ-oryzanol, none of the synthesized compounds inhibited the 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis.

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

Multistep syntheses of novel 17β-pyrazol-5'-ones in the Δ5-androstane series were efficiently carried out from pregnenolone acetate. A steroidal 17-carboxylic acid was first synthesized as a norpregnene precursor by the bromoform reaction and subsequent acetylation. Its CDI-activated acylimidazole derivative was then converted to a β-ketoester containing a two carbon atom-elongated side chain than that of the starting material. A Knorr cyclization of the bifunctional 1,3-dicarbonyl compound with hydrazine and its monosubstituted derivatives in AcOH under microwave heating conditions led to the regioselective formation of 17-exo-heterocycles in good to excellent yields. The suppression of an acid-catalyzed thermal decarboxylation of the β-ketoester and thus a significant improvement in the yield of the desired heterocyclic products could be achieved by the preliminary liberation of the arylhydrazines from their hydrochloride salts in EtOH in the presence of NaOAc. The reaction rates were found to depend on the electronic character of the substituent present in the phenylhydrazine applied. The antiproliferative activities of the structurally related steroidal pyrazol-5'-ones and their deacetylated analogs were screened on three human adherent breast cancer cell lines (MCF7, T47D and MDA-MB-231): the microculture tetrazolium assay revealed that some of the presented derivatives exerted cell growth inhibitory effects on some of these cell lines comparable to those of the reference compound, cisplatin.

Cell growth inhibitory effects of polyphenols with naphthalene skeleton against cisplatin-resistant ovarian cancer cells

Cisplatin often shows the drug resistance which could limit the chemotherapeutic efficacy. Thus, it is necessary to develop anticancer agents against cisplatin-resistant cancer cells. To identify pharmacophores exhibiting the cell growth inhibitory effect against cisplatin-resistant A2780/Cis ovarian cancer cells, we prepared 35 synthetic polyphenols bearing naphthalene skeleton including naphthalenyl chalcones, naphthalenyl flavones, naphthalenyl flavanones, 4,5-dihydro-1H-pyrazol-3-yl)naphthalen-2-ols, naphthalen-1-yl-N-phenyl-4,5-dihydro-1H-pyrazole-1-carbothioamides, and 4,5-dihydro-1H-pyrazol-3-yl)naphthalen-1-ol. The correlation between their inhibitory effects and structural properties was evaluated using hologram quantitative structure activity relationship and comparative molecular field analysis. The pharmacophores derived here can lead us to design new polyphenols against the growth of cisplatin-resistant cells.

Cellular Pharmacology of Palladinum(III) Hematoporphyrin IX Complexes: Solution Stability, Antineoplastic and Apoptogenic Activity, DNA Binding, and Processing of DNA-Adducts.

Two paramagnetic PdIII complexes of hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp), namely a dinuclear one [PdIII2(Hp-3H)Cl3(H2O)5]·2PdCl2, Pd1 and a mononuclear metalloporphyrin type [PdIII(Hp-2H)Cl(H2O)]·H2O, Pd2 have been synthesized reproducibly and isolated as neutral compounds at different reaction conditions. Their structure and solution stability have been assayed by UV/Vis and EPR spectroscopy. The compounds researched have shown in vitro cell growth inhibitory effects at micromolar concentration against a panel of human tumor cell lines. A DNA fragmentation test in the HL-60 cell line has indicated that Pd1 causes comparable proapoptotic effects with regard to cisplatin but at substantially higher concentrations. Pd1 and cisplatin form intra-strand guanine bis-adducts as the palladium complex is less capable of forming DNA adducts. This demonstrates its cisplatin-dissimilar pharmacological profile. The test for efficient removal of DNA-adducts by the NER synthesis after modification of pBS plasmids with either cisplatin or Pd1 has manifested that the lesions induced by cisplatin are far better recognized and repaired compared those of Pd1. The study on the recognition and binding of the HMGB-1 protein to cisplatin or Pd1 modified DNA probes have shown that HMG proteins are less involved in the palladium agent cytotoxicity.