Cancer Cell Line SKOV3 Research Articles

Anticarcinogenic and Antioxidant Action of an Edible Aquatic Flora Jussiaea repens L. Using In Vitro Bioassays and In Vivo Zebrafish Model.

Oxidative stress is the major cause of many health conditions, and regular consumption of antioxidants helped to encounter and prevent such oxidative stress-related diseases. Due to safety concerns over long-term uses of synthetic antioxidants, natural antioxidants are more preferred. The purpose of this study is to investigate the antioxidant and anticancer activities of Jussiaea repens L., a wild edible flora found in Manipur, India. The antioxidant activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), Ferric reducing antioxidant power (FRAP) assay and DNA-nicking assay. The anticancer activity was tested using five cancer lines viz., SKOV3 cells (ovarian), HeLa (cervical), MDA-MB-231 (breast), PANC-1 (pancreatic), and PC3 (prostate). The toxicity, developmental effect, antiproliferative activity was further tested using zebrafish embryos. The methanolic plant extract had higher polyphenol content than flavonoids. The in vitro study demonstrated a promising antioxidant capacity and DNA protection ability of this plant. The extract also showed cytotoxic activity against SKOV3, HeLa, MDA-MB-23, and PANC-1 cancer cell lines. The in vivo studies on zebrafish embryos demonstrated the extract’s ability to suppress the developmental process and elicited more cytotoxicity to cancer cells than developing zebrafish embryos. Moreover, the in vivo studies on zebrafish embryos also indicated the antiproliferative activity of J. repens L. extract.

Cytotoxicity of Ocimum basilicum and Impatiens walleriana Extracts on AGS and SKOV-3 Cancer Cell Lines by Flow Cytometry Analysis

Background: Numerous studies investigate finding new drug candidates with an increasing death rate caused by cancer. Nowadays, herbal medicine has been noticed again because of the many side effects of chemical drugs. Objectives: In the current study, anthocyanin and carotenoid types of compounds of Ocimum basilicum and Impatiens walleriana were determined and their cytotoxic effect on human gastric adenocarcinoma (AGS) and human ovarian carcinoma (SKOV-3) cancer cell lines were investigated. The cytotoxic effect of I. walleriana on cancer cells has not been reported so far. Methods: The amount of anthocyanin and carotenoid derivatives in these two plant species were investigated by biochemical tests, 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and flow cytometry methods were applied for the cytotoxicity effect of the extracts on the AGS and SKOV3 cancer cell lines. Cell necrosis and apoptosis were determined by annexin V-fluorescent isothiocyanate/propidium iodide (FITC/PI) staining and quantification by flow cytometry. Results: Ocimum basilicum and I. walleriana contained a noticeable amount of the mentioned compounds. According to the results, the lowest IC50 (Half- maximal inhibitory concentration) value with an amount of 2.5 ± 0.21 mg/mL that indicates the most cytotoxic extract on the AGS cancer cell line belonged to I. walleriana extract. Besides, the lowest IC50 value of O. basilicum was about 0.9 ± 0. 11 mg/mL on the SKOV3 cancer cell line. The flow cytometry analysis has also proved that the toxicity of O. basilicum is more than I. walleriana on the SKOV3 cell line and the toxicity of I. walleriana was higher than O. basilicum on the AGS cancer cell line. Conclusions: Ocimum basilicum and I. walleriana contain antioxidant compounds, which showed the cytotoxic effect on AGS and SKOV3 cancer cell lines. Further studies on animal models and subsequent trials are necessary for revealing the full potential of the extracts.

Fluorinated Cycloplatinated(II) Complexes Bearing Bisphosphine Ligands as Potent Anticancer Agents.

A family of cationic cycloplatinated(II) complexes [Pt(dfppy)(P^P)]Cl, dfppy = 2-(2,4-difluorophenyl)pyridine, incorporating bisphosphine ligands, P^P = bis(diphenylphosphino)methane (1, dppm), 1,2-bis(diphenylphosphino)ethane (2, dppe) and 1,2-bis(diphenylphosphino)benzene (3, dppbz), was prepared. The complexes were characterized by means of several analytical and spectroscopic methods. These complexes displayed acceptable stability in the biological environments which was confirmed by NMR, HR ESI-MS and UV-vis techniques. The antiproliferative properties of these complexes were evaluated by National Cancer Institute (NCI) at National Institutes of Health (NIH) against 60 different human tumor cell lines such as leukemia, melanoma, lung, colon, brain, ovary, breast, prostate and kidney. These complexes showed higher cytotoxicity than cisplatin against a wide variety of cancer cell lines such as K-562 (leukemia), HOP-92 (lung), HCT-116 (colon), OVCAR-8 (ovarian), PC-3 (prostate), MDA-MB-468 (breast), and melanoma cancer cell lines. Complex 3 as the most potent compound in this study furnished an excellent anti-proliferative activity compared to the cisplatin against Hela, SKOV3, and MCF-7 cancer cell lines. The main mode of the interaction of 1-3 with DNA was also determined using molecular docking studies.

Species D Adenoviruses as Oncolytic Viral Vectors.

Oncolytic adenoviruses (Ad) have shown promising results in the therapeutic treatment of cancer. Ad type 5 (Ad5) is the most extensively utilized Ad type. However, several limitations exist to using Ad5 as an oncolytic virus, including high levels of anti-Ad5 neutralizing antibodies in the population, binding of the Ad5 hexon to blood coagulation factor X leading to liver sequestration and toxicity, and reduced expression of the primary receptor CAR on many tumors. Here, we use in vitro methods to explore the oncolytic potential of four alternative Ad types (Ad26, 28, 45, and 48) belonging to the species D Ad subgroup and developed replication-competent species D Ads expressing the human sodium iodide symporter protein (hNIS) for combination radiovirotherapy. We evaluated the species D Ad vectors transduction, replication, cytotoxicity, and gene expression in six different cancer cell lines. Species D Ads showed the greatest transduction and cytotoxic killing in the SKBR3 breast cancer cells, followed by 293, A549, and HepG2 cells, however the cytotoxicity was less than the wild type Ad5 virus. In contrast, species D Ads showed limited transduction and cytotoxicity in the Hela and SKOV3 cancer cell lines. These species D Ad vectors also successfully expressed the hNIS gene during infection leading to increased iodide uptake in multiple cancer cell lines. These results, the low seroprevalence of anti-species D antibodies, and the lack of binding to blood coagulation FX, support further exploration of species D Ads as alternative oncolytic adenoviruses against multiple types of cancer.

Design, synthesis, and evaluation of new 2-oxoquinoline arylaminothiazole derivatives as potential anticancer agents

A series of novel 2-oxoquinoline derivatives containing arylaminothiazole were designed and synthesized as potential antitumor agents. The synthesized compounds were evaluated for their in vitro cytotoxicity activity against HeLa, NCI-H460, T24 and SKOV3 cancer cell lines using MTT assay. Among them, compound A7 exhibited the most potent activity against the test cancer cell lines, with the IC50 values ranged from 4.4 to 8.7 µM. The results of tubulin polymerization assay showed that compound A7 could inhibit tubulin polymerization in vitro. Meanwhile, molecular docking study revealed that A7 can bind to the colchicine site of tubulin and formed hydrogen bonds with key amino acid residues in the active site. Further mechanism study demonstrated that compound A7 blocked cell cycle arrest at G2/M phase, induced cell apoptosis and depolarized mitochondria of HeLa cells. Collectively, our findings suggest that A7 could serve as a promising lead for the development of more efficient microtubule polymerization inhibitors for cancer therapy.

Comparison of antioxidant and anti-bacterial activities of Ocimum basilicum and Impatiens walleriana and their anticancer properties on SKOV-3 cancer cell line

Comparison of antioxidant and anti-bacterial activities of Ocimum basilicum and Impatiens walleriana and their anticancer properties on SKOV-3 cancer cell line

Design, synthesis and antitumor evaluation of new 1,8-naphthalimide derivatives targeting nuclear DNA.

Four series of new 3-nitro naphthalimides derivatives, 4(4a‒4f), 5(5a‒5i), 6(6a‒6e) and 7 (7a‒7j), were designed and synthesized as antitumor agents. Methyl thiazolyl tetrazolium (MTT) screening assay results revealed that some compounds displayed effective invitro antiproliferative activity on SMMC-7721, T24, SKOV-3, A549 and MGC-803 cancer cell lines in comparison with 5-fluorouracil (5-FU), mitonafide and amonafide. Nude mouse xenotransplantation model assay results indicated that compounds 6b and 7b exhibited good invivo antiproliferative activity in MGC-803 xenografts in comparison with amonafide and cisplatin, suggesting that compounds 6b and 7b could be good candidates for antitumor agents. Gel electrophoresis assay indicated that DNA and Topo I were the potential targets of compounds 6b and 7b, and comet assay confirmed that compounds 6b and 7b could induce DNA damage, while the further study showed that the 6b- and 7b-induced DNA damage was accompanied by the upregulation of p-ATM, P-Chk2, Cdc25A and p-H2AX. Cell cycle arrest studies demonstrated that compounds 6b and 7b arrested the cell cycle at the S phase, accompanied by the upregulation of the expression levels of the antioncogene p21 and the down-regulation of the expression levels of cyclin E. Apoptosis assays indicated that compounds 6b and 7b caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-3, caspase-9 and PARP and the downregulation of Bcl-2. These mechanistic studies suggested that compounds 6b and 7b exerted their antitumor activity by targeting to DNA, thereby inducing DNA damage and Topo I inhibition, and consequently causing S stage arrest and the induction of apoptosis.

10-Methylthiocolchicine complexes with lithium, sodium, potassium, rubidium and cesium metal cations salts – Cytotoxic, semi-empirical and molecular modelling studies

Thiocolchicine (10-methylthiocolchicine) is a semi-synthetic alkaloid with notable cytotoxic activity. Complexes of 10-methylthiocolchicine with Li+, Na+, K+, Rb+ and Cs+ monovalent cations of perchlorates and iodides have been obtained and characterized by spectroscopic methods, semi-empirical studies and molecular modelling. An explanation of the chemical nature of complexes formed between this alkaloid and monovalent metal cations of perchlorate and iodide salts which are present in human daily life is important. Their activities as cytotoxic and antifungal agents were also tested against the SKOV-3 cancer cell line and for eight selected microfungi species, respectively. Biological tests indicated no antifungal properties for 10-methylthiocolchicine. Complexation of 10-methylthiocolchicine with monovalent metal cations significantly improved the anticancer potency (~IC50 = 4 nM) against the SKOV-3 cancer cell line.

Investigations of antioxidant potential and protective effect of Acanthophora algae on DNA damage: An electrochemical approach

In this paper, the electrochemical method was used as a rapid and sensitive method to measure the antioxidant activity of Acanthophora red macro-algae (collected from the Persian Gulf coast of Bushehr-Iran). The algae extract was obtained by a combination of maceration and microwave methods, and then the important volatile and bioactive compounds were identified by GC-Mass analysis. To prepare the sensor and improve the electrochemical signal, gold nanoparticles synthesized by the green method were used to modify the electrode surface. Differential pulse voltammetry method (DPV) was used to investigate the inhibitory effect of the extract on ABTS and DPPH radicals.To investigate the ability of the Acanthophora algae extract to prevent DNA damage induced by Fenton reaction, an electrochemical biosensor was designed based on the immobilization of human interleukin-2 (IL-2) gene probe on the surface of gold nanoparticle-modified carbon screen-printed electrode. Then, the protective effect of the algae extract was investigated by electrochemical impedance spectroscopy. Finally, the toxicity effect of Acanthophora algae extract on the HT-29, SKOV3, MCF-7, and SKMES-1 cancer cell lines was evaluated by MTT assay.

Abstract 968: Distinct pathways of DC-induced CD8+T cell differentiation revealed by single-cell mRNA sequencing analysis

Abstract Purpose of Study: Dendritic Cells (DC) maturing in the conditions of acute/early versus late/chronic inflammation (such as alpha-type-1-polarized DCs [αDC1s] and “standard” nonpolarized DCs; sDCs) deliver differential “signal 3” to resting T cells, resulting in their different induction of effector functions in tumor-specific CD8+ T cells. Here, using single-cell mRNAseq (scRNAseq), a unique technology allowing for unbiased analysis of gene expression (GEX), we evaluated the GEX patterns and cellular heterogeneity of CD8+ T cells expanded by cancer-cell loaded αDC1s or sDCs. Procedure: Freshly isolated autologous (compared to DCs) CD8+ T cells were in vitro sensitized for 1 week, using either αDC1s loaded with UV/gamma-radiation-killed ovarian cancer (OvCa) cell lines OVCAR or SKOV3, or sDCs loaded with the same antigens. αDC1s and sDCs not loaded with exogenous antigen were used as controls. The expanded CD8+ T cells were harvested, captured at the single-cell level and immobilized in a vertical flow array chip (VFAC), which contain 100-microchambers packed with 105 beads immobilizing 1010 oligo(dT) probes with unique cell-ID, UMI, and PCR-tags. Each cell was lysed and its mRNA was individually tagged with unique cell ID sequences prior to library preparation and targeted scRNAseq using a custom 94-gene inflammation RNA-seq panel was performed. Post-clustering (Scanpy), unsupervised cell-type identification (louvain), and downstream analyses were performed on GEX data to determine impact of αDC1s versus sDCs (loaded with OVCAR or SKOV3 versus not loaded with antigens) on the effector and memory pathways of differentiation of the expanded T cells and their unique functional status. Results: PCA and unsupervised clustering revealed sample groups with distinct phenotypic signatures associated with loaded versus unloaded aDC1s, with differential GEX subclusters identified for the αDC1- activated T cells (independently on DC loading with either OVCAR or SKOV3 cells) to include at least two populations with differential expression of genes typical of central memory, effector memory and effector cells (killer molecules and chemokine receptors typical of both lymphoid and peripheral homing potential). In sharp contrast, sDC1 activated T cell showed a more uniform gene distribution patterns lacking the effector T cell component. These differences correlated with the differential ability of αDC1- and sDC-activated T cells to respond to migrate to different chemokines and to recognize and kill cancer cells. Conclusion: scRNAseq was able to identify distinct single-cell T-cell phenotypes caused by induction of αDC1s or sDCs (loaded with OVCAR or SKOV3), consistent with the differential ability of these two DC types to induce effector, effector memory and central memory CD8+ T cells in response to different tumor targets and with their differential ability to modulate peripheral tissue homing patterns. Citation Format: Bowen Dong, Sarabjot Pabla, Vincent Giamo, Weijian Jiang, Kiyomi Taniguchi, Sean T. Glenn, Masataka Shirai, Pawel Kalinski. Distinct pathways of DC-induced CD8+T cell differentiation revealed by single-cell mRNA sequencing analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 968.

MiR-6086 inhibits ovarian cancer angiogenesis by downregulating the OC2/VEGFA/EGFL6 axis

miRNAs have emerged as a pivotal component of gene regulatory networks, mediating cytokines secretion, cell cycle, and differentiation regulation. However, how miRNAs collaborate with transcription factors and downstream effector proteins that determine the fate of ovarian cancer cells remains to be understood, especially regarding to mechanism of tumor angiogenesis regulation. Based on the qRT-PCR and IHC analysis, we found that miR-6086 was maintained a very low level both in ovarian cancer cell lines and tissues. Further, we identified OC2 and EGFL6 as the direct targets of miR-6086 by luciferase assay and we observed an inverse relationship between the expression of miR-6086 and the OC2/VEGFA/EGFL6 axis. The Western blotting analysis suggested that OC2 could directly upregulate VEGFA and indirectly up-regulate EGFL6 through VEGFA. Moreover, miR-6086 could indirectly downregulate VEGFA through OC2. In addition, miR-6086, siOC2 and siEGFL6 could negatively regulate the tumor growth and angiogenesis of ovarian cancer (Skov3) in the animal studies, with the inhibition rates of 77.07%, 69.89%, and 73.62%, respectively (**p < 0.01). Moreover, the tumor cell proliferation, migration, and invasion of ovarian cancer cell lines (Caov3 and Skov3) and vascular formation (HUVECs) were significantly suppressed in vitro, by decreasing the AKT/MAPK pathways (*p < 0.05). Taken together, our results reveal that miR-6086 can suppress the angiogenesis networks in ovarian cancer by down-regulating the OC2/VEGFA/EGFL6 axis, directly or indirectly, which may provide potential targets for tumor therapeutics.

Comparison of ultrastructural changes and the anticarcinogenic effects of thymol and carvacrol on ovarian cancer cells: which is more effective?

ABSTRACTOvarian cancer is the seventh most common cancer worldwide in women. Many anticancer drugs are currently used clinically have been isolated from plant species or are based on such substances. Thymol (5-methyl-2-isopropylphenol) and carvacrol are oxygenated aromatic compounds from the monoterpene group. They are the main constituents of thyme essential oil and show antiproliferative, antioxidant, and antiseptic properties. The aim of this study is to compare the antiproliferative and apoptotic effects of thymol and carvacrol on SKOV-3 ovarian cancer cell line. The cancer cells were treated with different concentrations of thymol and carvacrol (100, 200, 400, 600 µM) at 24 h and 48 h durations. The cell viability was investigated by MTT assay and analysis of apoptosis with annexin V assay was determined. The study show that thymol and carvacrol significantly induced apoptosis in all groups as dose and time-dependent (p < .05). The data in the present study demonstrated that thymol and carvacrol have apoptotic and antiproliferative properties in a concentration-dependent manner toward ovarian cancer cells. SKOV-3 cancer cell line was much more sensitive to the toxic effect of thymol than carvacrol.

Design, synthesis and biological evaluation of 3-nitro-1,8-naphthalimides as potential antitumor agents

A series of 3-nitro-naphthalimides 1(1a–1h) were designed and synthesized as antitumor agents. MTT assay results showed that all these compounds exhibited obvious antiproliferative activity against SKOV3, HepG2, A549, T-24 and SMMC-7721 cancer cell lines, while compound 1a displayed the best antiproliferative activity against HepG2 and T-24 cell lines in comparison with mitonafide, with IC50 of 9.2 ± 1.8 and 4.133 ± 0.9 μM, respectively. In vivo antiproliferative activity assay results showed that compound 1a exhibited good antiproliferative activity in the HepG2 and T-24 models, compared with mitonafide. Action mechanism results showed that compound 1a could induced the damage of DNA and the inhibition topo I, accompanying by inducing the G2-stage arresting and the apoptosis of T-24 cancer cells through up-regulating expression levels of cyclin B1, cdc 2-pTy, Wee1, γH2AX, p21, Bax and cytochrome c and down-regulating expression of Bcl-2.

Cytotoxic potentials of the culture extract of the endophytic Aspergillus niger strain karmalı isolated from Punica granatum against SKOV3 and A549 cancer cell lines

Cytotoxic potentials of the culture extract of the endophytic Aspergillus niger strain karmalı isolated from Punica granatum against SKOV3 and A549 cancer cell lines

1866 The Role of Microrna-424/503-Wee1 Axis in Ovarian Cancer Stem Like Cells

Study Objective We investigated the role of miR-424/503-WEE1 axis in ovarian cancer and its potential utility as a therapeutic target. Design To determine whether miR 424/503-WEE1 axis is associated with the generation of CSCs, we up/down-regulated miR 424/503-WEE1 axis in ovarian cancer sphere cells. Setting This study was performed in Pusan National University Hospital, Busan, Korea Patients or Participants The human epithelial ovarian cancer cell lines OVCAR3, SKOV3, and OVCAR429 were obtained from the Korean Cell Line Bank. Ovarian cancer cells were maintained in MEM (Life Technologies, Inc., Grand Island, NY, USA) supplemented with 10% fetal bovine serum and 100 μg/ml streptomycin in a humidified 5% CO2 incubator. Interventions In order to assess spheroid formation, approximately 5 × 103 cells were suspended in 10 mL of serum-free DMEM-F12, supplemented with 10 ng/mL basic fibroblast growth factor, 20 ng/mL epidermal growth factor and plated in an ultra-low attachment plate to prevent adherence. Spheres were counted at 14 days after plating. All experiments were performed in triplicate. Measurements and Main Results Firstly, we discovered that miR-424 and miR-503 are lowly expressed in ovarian cancer stem-like cells (CSCs) compared with non-CSCs. Over-expression of miR-424 and miR-503 resulted in decreased cancer colony formation, migration in ovarian cancer cell lines. Moreover, miR-424 and miR-503 over-expression caused inhibition of spheroid formation and the DNA damage repair pathway, while over-expression of Wee1 caused increased spheroid formation and cell survival in ovarian CSCs. Secondly, we found that the stem cell marker NANOG decreased miR-424 and miR-503 transcription in ovarian CSCs. In addition, miR-424 and miR-503 bind to the 3’ UTR of WEE1 to decrease its expression. Finally, we found that atorvastatin treatment increased miR-424 and miR-503 expression while it significantly decreased NANOG and WEE1 expression in ovarian CSCs. Conclusion Our findings indicate that increased WEE1 is an oncogenic marker for ovarian CSCs and is a potential target for CSC-specific therapy.

Exploitation of apple pomace towards extraction of triterpenic acids, antioxidant potential, cytotoxic effects, and inhibition of clinically important enzymes

Apple pomace (AP) utilised for analysis of triterpenic acids (TTAs) using HPLC-MS/MS. The methanol, ethanol and ethyl acetate extracts showed high phenolic content with significant antioxidant activity compared to chloroform and n-hexane. AP TTAs; ursolic acid, betulinic acid and maslinic acid showed potent antioxidant and enzyme inhibitory effects. The IC50 values were 13.2–30.8 μg/mL (tyrosinase), 19.6–42.5 μg/mL (xanthine oxidase) and 16.6–38.6 μg/mL (urease) for AP extracts and 8.4–25.8 μg/mL (tyrosinase), 12.6–30.2 μg/mL (xanthine oxidase) and 10.1–28.6 μg/mL (urease) for TTAs, compared to the positive controls; kojic acid (10.4 ± 0.06 μg/mL), allopurinol (9.6 ± 0.04 μg/mL) and thiourea (8.9 ± 0.02 μg/mL) towards respective enzymes. UA showed a competitive type of inhibition for tyrosinase, while BA showed a noncompetitive type of inhibition towards xanthine oxidase. In addition, the AP extracts and TTAs exerted significant cytotoxic effects towards the proliferation of cancer cell lines. AP methanol extract (IC50 of 38.5 ± 4.1, 47.1 ± 3.5, 70.6 ± 2.3, and 50.5 ± 3.9 μg/mL) and ursolic acid (IC50 of 6.5 ± 0.7, 15.5 ± 1.4, 20.8 ± 1.3, and 5.6 ± 0.8 μg/mL) showed prominent anticancer activity on Hela, Skov-3, Caski, and NCL cancer cell lines, respectively. Thus, this study shows that the AP & TTAs could be utilized for functional food development and as a potent antioxidant, anticancer, skin whitening, and anti-urolithic agents.

Estrogen-independent role of ERα in ovarian cancer progression induced by leptin/Ob-Rb axis.

Leptin induces ovarian cancer cell invasion via overexpression of MMP7, MMP9, and upA. In addition, the key role of ERα in leptin-increased cell growth was indicated. However, the influence of ER on leptin-mediated cell invasion remains still unknown. The present study was designed to evaluate the E2-independent effect of ERα/β on leptin-mediated cell invasion and cell proliferation in ovarian cancer. We utilized SKOV3 cancer (expressing OB-Rb and ERα/β, insensitive to estrogen) and OVCAR3 (expressing OB-Rb) cell lines to show the involvement of ER in leptin-mediated effects in an E2-independent manner. MTT, BrdU, and BD matrigel invasion assays were applied to analyze cell growth, proliferation, and invasion. The siRNA approach was used to confirm the role of ERα/β in leptin effects. Moreover, western blotting and Real-time PCR were employed to detect the OB-Rb, ER, MMP9/7, and upA proteins and mRNAs. Leptin, in the absence of E2, increased ERα expression in SKOV3 cells, which was attenuated using knockdown of OB-Rb gene by siRNA. The effect of leptin on the cell growth was promoted in the presence of PPT, but not in the presence of DNP and E2, which was lost when OB-Rb siRNA was transfected. Furthermore, ERα gene silencing and/or pre-incubation with ER antagonist (ICI 182,780, 10nM) significantly reduced cell invasion and MMP9 expression stimulated by leptin. In conclusion, our findings demonstrated that ERα, but not ERβ, is involved in leptin-induced ovarian cancer in an E2-independent manner, providing new evidence for cancer progression in obesity-associated ovarian cancer.

Synthesis and biological evaluation of potent benzoselenophene and heteroaromatic analogues of (S)-1-(chloromethyl)-8-methoxy-2,3-dihydro-1H-benzo[e]indol-5-ol (seco-MCBI).

A diverse series of compounds (18a–x) were synthesized from (S)-1-(chloromethyl)-8-methoxy-2,3-dihydro-1H-benzo[e]indol-5-ol (seco-MCBI) and benzoselenophene or heteroaromatic acids. These new compounds were evaluated for their cytotoxicity against the human gastric NCI-N87 and human ovarian SK-OV3 cancer cell lines. The incorporation of a methoxy substituent at the C-7 position of the seco-CBI unit enhances the cytotoxicity through its additional van der Waals interaction and gave a much higher potency than the corresponding seco-CBI-based analogues. Similarly, the seco-MCBI-benzoselenophene conjugates (18h–x) exhibited substitution effects on biological activity, and the N-butyramido and N-methylthiopropanamido analogues are highly potent, possessing >77- and >24-fold better activity than seco-MCBI-TMI for the SK-OV3 and NCI-N87 cell lines, respectively.

Novel triazole analogs of apigenin-7-methyl ether exhibit potent antitumor activity against ovarian carcinoma cells via the induction of mitochondrial-mediated apoptosis.

Ovarian cancer is one of the main causes of cancer-associated mortality across the world. Currently, ovarian cancer is mainly treated with chemotherapy. However, ovarian cancer is detected at advanced stages and chemotherapy has numerous side effects. In addition, the results of current chemotherapy on the treatment of ovarian cancer are less than satisfactory. Therefore, there is an urgent need to develop novel and more viable chemotherapeutic agents that can be used to treat ovarian cancer. The present study was designed to synthesize a series of novel triazole analogs of the bioactive apigenin-7-methyl ether to evaluate its anticancer activity against three human ovarian cancer cell lines. A total of eight novel triazole derivatives were synthesized and screened for their anticancer activity. Of all the derivatives, a derivative named 3d exhibited significant and dose-dependent anticancer activity against the SKOV3 ovarian cancer cell line. The IC50 of 3d was found to be 10 µM against the SKOV3 cancer cell line. It was also observed that 3d induced apoptosis in SKOV3 cancer cells through the accretion of reactive oxygen species and reduction in mitochondrial membrane potential. The molecule also modulated the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein. Taken together, these results showed that the apigenein-7-methyl ether novel derivative 3d may prove an important lead molecule for the treatment of ovarian cancer.

Growth inhibition and apoptosis induction in two types of women cancer cell lines using laser ablated silver nanoparticles in polyvinylpyrrolidone solution

Silver nanoparticles (AgNPs) coated with polyvinylpyrrolidone (PVP) was prepared by pulsed laser ablation method inPVP solution, 1000 pluse was used with laser energy of 800 mJ/pulse. Formation of AgNPs-PVP was confirmed by UVvisiblespectrophotometer detecting surface plasmon resonance chang in the abilation solution. Concentration of AgNPs, sizedistribution, and surface charge of the ablated AgNPs in the produced solution was determined using atomic absorbtion spectroscopyand zeta potential analysis respectivly. Nanoparticles shape was determined using transmission electron microscopeimaging. Ability of the senthezied AgNPs to inhibit the growth of cancer cells was compared to that of normal fibroblast cellsusing two cancer cell lines (HeLa and SKOV-3) in different concentrations (0.78, 1.56, 3.125, 6.25, 12.5 and 25μg/ml). Theapoptosis events were also detected in both types of cancer cell lines using mitochondrial membrane permeability, nuclearmorphology, and genomic DNA fragmentation. The contribution of AgNPs to the levels of glutathione s-transferase was alsodetermined. According to the results, AgNPs size was 28.43nm with spherical shape and peak UV-Vis absorbance rangedbetween 402-410nm. Concentration of AgNPs in ablated solution was 50μg/ml and used as stock concentration in cell linesexperiments. Ablated silver nanoparticles was capable of inhibit the growth of both HeLa and SKOV-3 cancer cell lines indose and time dependent manner, whereas it was less inhibitory against normal fibroblast cells. All three apoptosis detectionmethod conducted indicated positive characteristics for apoptosis, while GSH levels did not varied significantly in both HeLaand SKOV-3 cells.Keywords: AgNPs, cancer cells, metal silver, Cytotoxicity, MTP, DNA fragmentation, GSH.