Chemical Characterization,Antiproliferative and Antioxidant Activities of Polyunsaturated Fatty Acid-Rich Extracts from Chlorella sp. S14

Microalgae is a rich source of polyunsaturated fatty acid. This study was conducted to identify and isolate microalgal strain with the potentials for producing polyunsaturated fatty acids (PUFAs) and determine its cytotoxic effect on some cancer cells. The algal strain (Chlorella sp. S14) was cultivated using modified BG-11 media, and algal biomass obtained was used for fatty acid extraction. Gas chromatographic–mass spectrometry was used to identify and quantify the levels of the fatty acid constituents. The total content of monounsaturated fatty acids (1.12%) was low compared to polyunsaturated fatty acids (PUFAs) (52.87%). Furthermore, n-3 PUFAs accounted for (12.37%) of total PUFAs with the presence of α-linolenic acid (2.16%) and cis-11,14,17-eicosatrienoic acid (2.16%). The PUFA-rich extract did not exhibit a cytotoxic effect on normal cells. Treatment with the PUFA-rich extract (150 µg/mL) significantly reduced cell viability in MCF-7 (31.58%) and A549 (62.56%) cells after the 48 h treatment. Furthermore, treatment of MCF-7 with fatty acid extracts (125 and 150 µg/mL) showed a significant reduction in MDA levels, increase in catalase activities and decrease in GSH level compared to untreated cells. However, a slight decrease in MDA level was observed in A549 cells after the 48 h treatment. There are no significant changes in catalase activities and GSH level in treated A549 cells. However, a slight reduction of NO levels was observed in treated MCF-7 and A549 cells. These results indicate the potentials of PUFA-rich extracts from Chlorella sp. S14 to reduce viability and modulate redox status in A549 and MCF-7 cells.     

Discovery of Leptulipin,a New Anticancer Protein from theIranian Scorpion,Hemiscorpius lepturus

Cancer is one of the leading causes of mortality in the world. Unfortunately, the present anticancer chemotherapeutics display high cytotoxicity. Accordingly, the discovery of new anticancer agents with lower side effects is highly necessitated. This study aimed to discover an anticancer compound from Hemiscorpius lepturus scorpion venom. Bioactivity-guided chromatography was performed to isolate an active compound against colon and breast cancer cell lines. 2D electrophoresis and MALDI-TOF were performed to identify the molecule. A partial protein sequence was obtained by mass spectrometry, while the full-length was deciphered using a cDNA library of the venom gland by bioinformatics analyses and was designated as leptulipin. The gene was cloned in pET-26b, expressed, and purified. The anticancer effect and mechanism action of leptulipin were evaluated by MTT, apoptosis, and cell cycle assays, as well as by gene expression analysis of apoptosis-related genes. The treated cells displayed inhibition of cell proliferation, altered morphology, DNA fragmentation, and cell cycle arrest. Furthermore, the treated cells showed a decrease in BCL-2 expression and an increase in Bax and Caspase 9 genes. In this study, we discovered a new anticancer protein from H. lepturus scorpion venom. Leptulipin showed significant anticancer activity against breast and colon cancer cell lines.     

CuO NPs@Starch as a novel chemotherapeutic drug for the treatment of several types of gastrointestinal system cancers including gastric,pancreatic, and colon cancers

Copper oxide nanoparticles were successfully synthesized through a simple and ‘green’ route using starch as a capping and stabilizing agent under ultrasonic irradiation in alkaline medium. Unique reaction condition was prepared by ultrasonic irradiation, releasing the stored energy in the collapsed bubbles and heats the bubble contents that leads to Cu(II) reduction in the presence of starch. The obtained nanoparticle (CuO NPs@Starch) was characterized by advanced physical and chemical techniques like Transmission Electron Microscope (TEM), Fourier-transform infrared spectroscopy (FTIR), Uv–Vis spectroscopy, scanning electron microscopy (SEM), X-ray Diffraction (XRD) and energy-dispersive X-ray analysis (EDX). The properties of CuO NPs@Starch against gastric cancer (AGS and KATO III), pancreatic cancer (AsPC-1 and MIA PaCa-2), and colon cancer (HCT 116 and HCT-8) were evaluated. The viability of malignant cancer cell lines reduced dose-dependently in the presence of CuO NPs@Starch. After clinical study, CuO NPs@Starch can be utilized as an efficient drug in the treatment of gastric, pancreatic, and colon cancers in humans.     

An In Vitro Anticancer,Antioxidant, and Phytochemical Study on Water Extract of Kalanchoe daigremontiana Raym.-Hamet and H. Perrier

Kalanchoe species are succulents with anti-inflammatory, antioxidant, and analgesic properties, as well as cytotoxic activity. One of the most popular species cultivated in Europe is Kalanchoe daigremontiana Raym.-Hamet and H. Perrier. In our study, we analyzed the phytochemical composition of K. daigremontiana water extract using UHPLC-QTOF-MS and estimated the cytotoxic activity of the extract on human ovarian cancer SKOV-3 cells by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, flow cytometry, luminometric, and fluorescent microscopy techniques. The expression levels of 92 genes associated with cell death were estimated via real-time PCR. The antioxidant activity was assessed via flow cytometry on human keratinocyte HaCaT cell line. The DPPH (2,2-diphenyl-1-picrylhydrazyl) radical and FRAP (ferric-reducing antioxidant power) assays were also applied. We identified twenty bufadienolide compounds in the water extract and quantified eleven. Bersaldegenin-1,3,5-orthoacetate and bryophyllin A were present in the highest amounts (757.4 ± 18.7 and 573.5 ± 27.2 ng/mg dry weight, respectively). The extract showed significant antiproliferative and cytotoxic activity, induced depolarization of the mitochondrial membrane, and significantly arrested cell cycle in the S and G2/M phases of SKOV-3 cells. Caspases-3, 7, 8, and 9 were not activated during the treatment, which indicated non-apoptotic cell death triggered by the extract. Additionally, the extract increased the level of oxidative stress in the cancer cell line. In keratinocytes treated with menadione, the extract moderately reduced the level of oxidative stress. This antioxidant activity was confirmed by the DPPH and FRAP assays, where the obtained IC₅₀ values were 1750 ± 140 and 1271.82 ± 53.25 μg/mL, respectively. The real-time PCR analysis revealed that the extract may induce cell death via TNF receptor (tumor necrosis factor receptor) superfamily members 6 and 10.     

Cancer Initiation,Progression and Resistance: Are Phytocannabinoids from Cannabis sativa L. Promising Compounds?

Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from Cannabis sativa L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for Cannabis sativa L. and the ongoing clinical trials.     

Alnus sibirica Compounds Exhibiting Anti-Proliferative,Apoptosis-Inducing,and GSTP1 Demethylating Effects on Prostate Cancer Cells

Alnus sibirica (AS) is distributed in Korea, Japan, China, and Russia and has reported anti-oxidant, anti-inflammatory, and reducing activities on atopic dermatitis-like skin lesions, along with other beneficial health properties. In the present study, we tried to prove the cancer-preventive activity against prostate cancer. The extracted and isolated compounds, oregonin (1), hirsutenone (2), and hirsutanonol (3), which were isolated from AS, were tested for anti-proliferative activity. To do this, we used the MTT assay; NF-κB inhibitory activity, using Western blotting; apoptosis-inducing activity using flow cytometry; DNA methylation activity, using methylation-specific polymerase chain reaction in androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines. The compounds (1–3) showed potent anti-proliferative activity against both prostate cancer cell lines. Hirsutenone (2) exhibited the strongest NF-κB inhibitory and apoptosis-inducing activities compared with oregonin (1) and hirsutanonol (3). DNA methylation activity, which was assessed for hirsutenone (2), revealed a concentration-dependent enhancement of the unmethylated DNA content and a reduction in the methylated DNA content in both PC-3 and LNCaP cells. Overall, these findings suggest that hirsutenone (2), when isolated from AS, may be a potential agent for preventing the development or progression of prostate cancer.     

Novel Schiff base ligand and its metal complexes with some transition elements. Synthesis,spectroscopic, thermal analysis,antimicrobial and in vitro anticancer activity

A novel Schiff base ligand (H₂L) was prepared through condensation of 2,6‐diaminopyridine and o‐benzoylbenzoic acid in a 1:2 ratio. This Schiff base ligand was characterized using elemental and spectroscopic analyses. A new series of Cr(III), Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) metal complexes of H₂L were prepared and characterized using elemental analysis, spectroscopy (¹H NMR, mass, UV–visible, Fourier transform infrared, electron spin resonance), magnetic susceptibility, molar conductivity, X‐ray powder diffraction and thermal analysis. The complexes are found to have trigonal bipyramidal geometry except Cr(III), Mn(II) and Fe(III) complexes which have octahedral geometry based on magnetic moment and solid reflectance measurements. The infrared spectral studies reveal that H₂L behaves as a neutral bidentate ligand and coordinates to the metal ions via the two azomethine nitrogens. ¹H NMR spectra confirm the non‐involvement of the carboxylic COOH proton in complex formation. The presence of water molecules in all reported complexes is supported by thermogravimetric studies. Kinetic and thermodynamic parameters were determined using Coats–Redfern and Horowitz–Metzger equations. The synthesized ligand and its complexes were screened for antimicrobial activities against two Gram‐positive bacteria (Bacillus subtilis and Staphylococcus aureus), two Gram‐negative bacteria (Escherichia coli and Neisseria gonorrhoeae) and one fungus (Candida albicans). Anticancer activities of the ligand and its metal complexes against human breast cancer cell line (MCF7) were investigated. Copyright © 2016 John Wiley & Sons, Ltd.     

HPV在宫颈炎、宫颈癌前病变、宫颈癌中的检测及其临床意义研究

目的研究并探讨人乳头状瘤病毒(human papillomavirus,简称HPV)在宫颈炎、宫颈癌前病变、宫颈癌中的检测价值及临床意义。方法选取菏泽市妇幼保健院2014年1月—2016年12月期间收治的120例慢性宫颈炎患者、90例宫颈癌前病变患者、60例宫颈癌患者作为研究对象,分别设置为宫颈炎组、癌前病变组、宫颈癌组,并将癌前病变组分为CIN Ⅰ级、CIN Ⅱ级、CIN Ⅲ级,所有患者均接受HPV检测,比较其HPV阳性率、HPV DNA负荷载量、HPV感染持续时间,计算HPV感染持续时间、HPV DNA负荷载量与宫颈癌发生的相关性。结果宫颈炎组、癌前病变组、宫颈癌组的HPV阳性率、HPV DNA负荷载量、HPV感染持续时间比较,差异均具有统计学意义(P0.05),从高至低依次为宫颈癌组、癌前病变组、宫颈炎组,且不同分级宫颈癌前病变患者的HPV DNA负荷载量、HPV感染持续时间均存在显著差异(P0.05);经相关性分析,HPV感染持续时间、HPV DNA负荷载量均与宫颈癌的发生密切相关,呈正相关。结论HPV感染可能参与到宫颈癌前病变、宫颈癌的发生、发展中,开展HPV检测可对宫颈癌前病变、宫颈癌进行筛查,有利于宫颈癌的防治。     

Synthesis,anticancer activity,and molecular docking of new pyrazolo[1,5-a]pyrimidine derivatives

The reaction of 3-aminopyrzoles with dimethylamino-acrylonitrile derivatives was utilized for the production of new functionalized pyrazolopyrimidine compounds 4a-c and 6a-c. The structures of the obtained pyrazolopyrimidines were characterized by the different spectroscopic measurements (IR, NMR, and mass analyses). The DFT quantum chemical calculations were applied to the determination of the HOMO-LUMO energies and Mulliken atomic charges. The investigated derivatives exhibited a low HOMO-LUMO energy gap, ranging from 2.70 to 2.34 eV, 4c and both 4b and 6b, respectively. Furthermore, the anticancer activities of the synthesized compounds have also been investigated against four cancer cells as well as normal cells (WI38). The investigated compounds demonstrated an impressive cytotoxic effect on MCF-7 and Hep-2 cells. On comparison with 5-fluorouracil, pyrazolopyrimidines 6a–c showed promising cytotoxic action against MCF-7 and Hep-2, with IC₅₀ values of 18.31–26.51 and 24.15–27.16 μM, respectively. Molecular docking of the prepared pyrazolopyrimidines 4 and 6 with the crystal structure of the KDM5A protein, obtained from the PDB, revealed the types of the protein's binding sites.     

Green formulation,chemical characterization,and antioxidant,cytotoxicity, and anti-human cervical cancer effects of vanadium nanoparticles: A pre-clinical study

In this study, V₂O₅ nanoparticles were synthesized in an aqueous medium using Calendula officinalis extract as stabilizing and reducing agents. The synthesized nanoparticles (VNPs@C.officinalis) were characterized using different techniques including UV–Vis. and FT-IR Spectroscopy, X‐ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and Energy Dispersive X-ray Spectrometry (EDS). According to the XRD analysis, 28.83 nm was measured for VNPs@C.officinalis crystal size. SEM images exhibited a uniform spherical morphology in size of 38.14 nm for the biosynthesized nanoparticles. To survey the cytotoxicity and anti-human cervical cancer effects of C. officinalis aqueous extract and vanadium nanoparticles, MTT assay was used on C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3, and LM-MEL-41 cell lines. The IC50 of the vanadium nanoparticles were237, 259, 226, 409, 335, and 192 µg/mL against C-33 A [c-33a], SiHa, Ca Ski, DoTc2 4510, HT-3, and LM-MEL-41 cell lines, respectively. To survey the antioxidant properties of Calendula officinalis aqueous extract and vanadium nanoparticles, the DPPH test was used. The vanadium nanoparticles inhibited half of the DPPH molecules in a concentration of 125 µg/mL. As mentioned, the vanadium nanoparticles had significant antioxidant and anti-human cervical cancer effects.     

Dietary Polyphenols: Extraction,Identification, Bioavailability,and Role for Prevention and Treatment of Colorectal and Prostate Cancers

Fruits, vegetables, and other edible plants in our diet have numerous health benefits, due to the bioactive compounds in these food items, including polyphenols. These plants are a rich and promising source of natural products and phytochemicals that can be used to treat and prevent numerous diseases and prevent the progression of cancer. Dietary polyphenols exhibit chemo-preventive and therapeutic effects against various ailments, including several types of cancer. The current study focuses on polyphenol’s traditional and advanced extraction methods, with supercritical extraction as a novel approach. It also deals with their identification, bioavailability, and role in preventing and treating colorectal and prostate cancers. Additionally, the article covers the literature that deals with the anticancer activities of polyphenols, as well as their potential use as anticancer agents.     

Design,Synthesis, and Biochemical Evaluation of New Triazole Derivatives as Aurora-A Kinase Inhibitors

Aurora-A kinase, a key mitosis regulator, is expressed in a cell cycle-dependent manner and has an essential role in maintaining chromosomal stability and the normal progression of the cell through mitosis. Aurora-A kinase is overexpressed in many malignant solid tumors, such as breast, ovarian, colon, and pancreatic cancers. Thus, inhibiting Aurora-A kinase activity is a promising approach for cancer treatment. Here, new triazole derivatives were designed as bioisosteric analogues of the known inhibitor JNJ-7706621. The new compounds showed interesting inhibitory activity against Aurora-A kinase, as attested by IC₅₀s in the low to submicromolar range.     

Bioactivity-guided isolation of new antiproliferative compounds from Juniperus foetidissima Willd.

Based on a literature survey on cytotoxic medicinal plants, Juniper species were identified as interesting source of antitumor compounds. Using bioassay-guided fractionation against Caov-4 cancer cells on acetone extract of leaves and branchlets of Juniperus foetidissima led to the isolation of a new 3H-benzofuaran-2-one: 4-methyl-3-methoxy-3H-benzofuaran-2-one (1), a new sesquiterpene: 4,9(α)-dihydroxy-nardosin-6-en (2) and an already known labdane-type diterpene: 15-hydroxy-8(17),13(E)-labdadiene-19-carboxilic acid (3). Compounds 1–3 exhibited cytotoxic effects, with moderate cytotoxicity against the EJ-138 bladder and CAOV-4 ovary cancer cell lines.