Adenocarcinoma Cancer Cell Lines Research Articles

Theoretical and experimental study of gold(III), palladium(II), and platinum (II) complexes with 3-((4-nitrophenyl)thio)phenylcyanamide and 2,2′-bipyridine ligands: Cytotoxic activity and interaction with 9-methylguanine

The new gold(III), palladium(II), and platinum(II) complexes with 3-((4-nitrophenyl)thio)phenylcyanamide (HL) and 2,2′-bipyridine (bpy) ligands of formula [M(bpy)LCl] (M = Pd(II),1, Pt(II), 2) or [Au(bpy)LCl]Cl, 3, have been synthesized and fully characterized. The cytotoxicity of free ligands and complexes 1–3 were evaluated against HT-29 (colorectal adenocarcinoma), MCF-7 (breast), and HeLa (human squamous cervical adenocarcinoma) cancer cell lines along with MRC-5 non-tumorigenic cells (human lung fibroblasts) and their activity has been compared to the familiar platinum-based anticancer agent cisplatin. The free ligands bpy and HL were ineffective against the cancer cell lines. However, the complexes 1–3 showed a significant in vitro antitumor activity with IC50 values in the low micromolar. The complexes 1–3 were revealed to produce cellular reactive oxygen species (ROS). The most potent ROS producer, complex 3, also elicited the highest cytotoxicity. The interaction of 9-methylguanine (9-MeG-N7) with complexes 1–3 was studied by 1H NMR and mass spectroscopy. Furthermore, DFT calculations have been performed on complexes 1–3 and also [M(bpy)(L)(9-MeG-N7)](NO3)(M = Pd(II), 4, Pt(II), 5) or [Au(bpy)(L)(9-MeG-N7)](NO3)2, 6, using the BP86-D and B3LYP* functionals to provide a complete rationalization of their structures and to describe their electronic structures. The energy decomposition analysis (EDA) gave a clear understanding of the bonding for all complexes 1–6 showing that the interactions are mostly governed by electrostatic ones. Strong interactions occurred between the chlorine anion and the metallic fragment, but weakened between 9-methylguanine and the metallic fragment, in agreement with the electron transfers and the interaction energies.

Abstract 4921: TGF-beta signaling proteins and CYP24A1 may serve as surrogate markers for progesterone calcitriol treatment in ovarian and endometrial cancers of different histological types

Abstract Strategies are needed to coordinately block drivers and induce suppressors of cancer to reduce incidence and improve outcomes for individuals with inherited or acquired risk. We previously reported the chemopreventive and therapeutic efficacy of the combination of progestin and calcitriol in transformed and malignant endometrioid endometrial cancer and in ovarian cancer models involving attenuated expression of TGF-β signaling proteins and progestin-mediated inhibition of calcitriol-induced CYP24A1 expression. This study aims to expand the applications for this combination to other subtypes of endometrial and ovarian cancers including those with mutations in ARID1A or PIK3CA, DNA mismatch repair deficiency or BRCA1-null status. The end points for this in vitro investigation included assessments of cell growth and the expression of TGF-β ligands, receptors, SMAD proteins and CYP24A1. Treatment of ovarian clear cell carcinoma, endometrioid carcinoma, papillary serous adenocarcinoma, BRCA1 null, and DNA mismatch repair deficient endometrial cancer cell lines with progesterone alone or in combination with calcitriol inhibited cell growth and expression of TGF-β1, TGF-β2, TGF-Rβ1, TGF-βR2, pSMAD2/3 and CYP24A1. Expression of TGF-βR3, SMAD-4, PR and VDR was not altered in any cell line tested except, ES-2, where VDR expression was upregulated in response to treatment. These results suggest that progesterone alone and progesterone-calcitriol combination have broad application in both chemopreventive and therapeutic settings that merit further development in a wide variety of ovarian and endometrial cancers, including those derived from germline or somatic mechanisms. Moreover, our data suggest that TGF-β signaling proteins and CYP24A1 may be effective surrogate markers indicative of treatment response. Citation Format: Ana Paucarmayta, Hannah Taitz, Yovanni Casablanca, Gustavo C. Rodriguez, G L. Maxwell, Kathleen M. Darcy, Viqar Syed. TGF-beta signaling proteins and CYP24A1 may serve as surrogate markers for progesterone calcitriol treatment in ovarian and endometrial cancers of different histological types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4921.

Theoretical, antimicrobial, antioxidant, in vitro cytotoxicity, and cyclin-dependent kinase 2 inhibitor studies of metal(II) complexes with bis(imidazol-1-yl)methane-based heteroscorpionate ligands

A series of C-centered heteroscorpionate-based homoleptic manganese(II), nickel(II), and copper(II) complexes of type [M(L1–3)2] (1–9) have been synthesized by using the ligands (2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL1), (4-diethylamino-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL2) and (5-bromo-2-hydroxyphenyl)bis(imidazol-1-yl)methane (HL3). The geometric parameters of the complexes were determined using UV-vis and theoretical studies suggesting distorted octahedral geometry around metal(II) ion. Frontier molecular orbital analysis supports bioefficacy of the complexes. Antimicrobial activity of the metal(II) complexes were determined against two Gram(–ve) (Escherichia coli and Klebsiella pneumoniae) and two Gram(+ve) (Bacillus cereus and Staphylococcus aureus) bacteria, and three fungal (Candida albicans, Candida glabrata, and Candida krusei) strains. Antioxidant activity of nickel(II) and copper(II) complexes were evaluated against ABTS, DPPH, and H2O2 free radicals. In vitro cytotoxicity activity of nickel(II) and copper(II) complexes against human breast adenocarcinoma (MCF-7), cervical (HeLa), and lung (A549) cancer cell lines along with one normal human dermal fibroblasts (NHDF) cell line were carried out by MTT assay, which shows the potent activity of copper(II) complex 8 with respect to the standard drug cisplatin. Molecular docking studies evidence the interaction of complexes with cyclin-dependent kinase 2 receptor (CDK2).

Influence of Fe doping on structural, physicochemical and biological properties of CdSe nanoparticles

We synthesized pure and Fe doped CdSe nanoparticles (NPs) (Fe@CdSe NPs) with different dopant concentrations 5%, 10%, 15% using mercaptoethanol (ME) as a capping agent via precipitation technique (PT). As-synthesized NPs phase clarity was confirmed with the help of powder X-ray diffraction (P-XRD), and the calculated crystallite size was found to be ∼1.2 nm (±0.1) using by Scherer method. The optical band gap (Eg) values were depicted by UV–Visible spectroscopy with the help of K-M function (Kubelka-Munk). The Fourier transform infrared (FT-IR) and FT-Raman spectrometer were used to analyze the existence of functional groups and various vibrational modes in the synthesized NPs. The structural and expected elemental compositional properties were examined by using both transmission electron microscope (TEM) and energy dispersive spectroscopy (EDAX). In addition, magnetic property of synthesized NPs was measured using vibrating scanning magnetometer (VSM). Further, the impedance spectroscopy was employed to estimate the dielectric relaxation of the samples at various temperatures (303, 323, 343 and 373 K) with different frequency range. The synthesized pure and Fe@CdSe NPs were employed in photocatalytic degradation by methylene blue (MB) dye under visible region (664 nm). It resulted in the enhancement of photocatalytic dye degradation when compared to pure CdSe NPs. Moreover, the cytotoxicity of the synthesized NPs was studied on MCF-7 (human breast adenocarcinoma cancer cell lines), and we found that the CdSe NPs could inhibit cell growth by dose dependent inhibition (DDI).

Cycloschimperols A and B, new cytotoxic cycloartane triterpenoids from Euphorbia schimperi

Two new cycloartane-type triterpenoids, cycloschimperols A [cycloart-20,24-dien-3β-ol] (3) and B [26,27-dinor-3β-hydroxy cycloartan-25-al] (4) and two known compounds, 24-methylenecycloartane (1) and cycloart-25-en-3-one (2) were separated from the aerial parts of Euphorbia schimperi C. Presl (Euphorbiaceae). The structural characterization of these metabolites was achieved by various spectroscopic analyses, including 1D and 2D NMR and HRESIMS as well as comparison with the published data. The cytotoxic activities of these metabolites were assessed towards breast adenocarcinoma (MCF-7), human hepatocellular carcinoma (HepG2), and colorectal adenocarcinoma (HCT-116) cancer cell lines using sulphorhodamine B assay (SRB). Compounds 2 and 4 had the most potent cytotoxic profile against the tested cells lines with IC50s ranging from 1.4 to 4.7 μM, in comparison to doxorubicin (IC50 0.18, 0.60, and 0.20 μM, respectively).

Crystal structure, cytotoxicity and biological activity of hydrogen bonded networks based on dimethyltin (IV) and bipodal ligands

The supramolecular complexes (SC) of the type [Me2SnCl2L], L = 2,2′-bipyridine (2,2′-bpy), SC 1, 4,4′-bipyridine (4,4′-bpy), SC 2, and (1,10-phenanthroline), SC 3, have been synthesized and structurally characterized by elemental analysis, FT-IR, UV–Vis, 1H and 13C NMR spectra and X-ray single crystal. The X-ray data of SC 1 and SC 2 exhibited 1:1 stoichiometry for the dimethyltin dichloride: bipodal ligand. The structure of SC 1 extends along the a-axis in a parallel way forming 1D-chains via H-bonds while they further propagate creating 2D-network via extensive H-bonds. The extending structure of the SC 2 along the a-axis consists of parallel 1D-chains via H-bonds creating the A … A … A fashion. Molecular modeling studies of SC 3 indicated that Sn(IV) center acquires N2C2Cl2 octahedral geometry. The tested compounds SC 1, SC 2 and SC 3 were found to inhibit cell proliferation and induce high percent of apoptotic towards human breast adenocarcinoma (MCF7), liver carcinoma (HEPG2), colorectal carcinoma (HCT-116), cervical carcinoma (HELA) and prostate cancer (PC3) cell lines in vitro model within short times of treatment. The anti-Oxidant and anti-hemolytic assays employ that SC 1 exhibits moderate antioxidant activity as well as the most potent anti-hemolysis activities compared with ascorbic acid. The antimicrobial assessment has been also studied by disc diffusion method.

(Invited) Biological Multiphoton Imaging Techniques for Tracking Non-Fluorescent Carbon Nanomaterials

Multiphoton Microscopy (MPM) has enabled an unprecedented level of dynamic exploration within living cells and organisms. The physical principle behind this imaging technique involves the use of near-infrared femtosecond lasers to excite optical processes in fluorescent molecules using two or more photons1. The use of long wavelengths (700 nm – 1000 nm) enables deep tissue penetration (up to 1000 μm) without inducing harmful biological effects. Previous studies include the examination of membrane potentials on the single-molecule scale2, the non-invasive observation of embryo development3, and the simultaneous multiplane imaging of calcium transportation in transgenic mice4. An excellent review of this field can be found in the literature5. Herein we demonstrate a novel multiphoton-based technique for imaging negligible-to-non-fluorescent carbon-based nanomaterials such as C60 fullerenes, single-walled carbon nanotubes, and graphene, which usually can only be imaged by conjugation of specific fluorescent tracers thereby altering their inherent dynamics within biological systems. More specifically, we demonstrate optical and photoluminescent activity in water-soluble C60-serinol, highly enriched (95 %) metallic and semiconducting single-walled carbon nanotubes, and graphene. This multiphoton imaging technique was also applied to in vitro and in vivo animal model studies. Various concentrations of the above-mentioned nanomaterials were given to human pancreatic ductal adenocarcinoma (Panc-1) and hepatocellular carcinoma (Heb3B) cancer cell lines, as well as normal, healthy pancreatic ductal epithelial cells (HPDE). In all cases, imaging of these nanomaterials was possible using the MP imaging technique even though the nanomaterials exhibit weak, almost zero inherent fluorescent properties. We also examined the ability to image these nanomaterials, real-time, in vivo, using mice with orthotopic 4T1 breast tumors. Finally, we also include a range of spectroscopy data to examine the specific optical characteristics of the carbon nanomaterials. References Denk, W.; Strickler, J.; Webb, W. Science 1990, 248, (4951), 73-76.Peleg, G.; Lewis, A.; Linial, M.; Loew, L. M. Proceedings of the National Academy of Sciences 1999, 96, (12), 6700-6704.Chu, S.-W.; Chen, S.-Y.; Tsai, T.-H.; Liu, T.-M.; Lin, C.-Y.; Tsai, H.-J.; Sun, C.-K. Opt. Express 2003, 11, (23), 3093-3099.Cheng, A.; Goncalves, J. T.; Golshani, P.; Arisaka, K.; Portera-Cailliau, C. Nat Meth 2011, 8, (2), 139-142.Hoover, E. E.; Squier, J. A. Nat Photon 2013, 7, (2), 93-101.

4-(4-Bromophenyl)-thiazol-2-amine derivatives: synthesis, biological activity and molecular docking study with ADME profile

In order to overcome the challenges of microbial resistance as well as to improve the effectiveness and selectivity of chemotherapeutic agents against cancer, a novel series of 4-(4-bromophenyl)-thiazol-2-amine derivatives was synthesized and its molecular structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were further evaluated for their in vitro antimicrobial activity using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. The antimicrobial activity results revealed that compound p2, p3, p4 and p6 exhibited promising antimicrobial activity that are comparable to standard norfloxacin (antibacterial) and fluconazole (antifungal). Anticancer screening results demonstrated that compound p2 was found to be the most active one against cancer cell line when compared to the rest of the compounds and comparable to the standard drug (5-fluorouracil). The molecular docking study demonstrated that compounds, p2, p3, p4 and p6 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and showed promising ADME properties.

Synthesis, molecular modelling and biological significance of N-(4-(4-bromophenyl) thiazol-2-yl)-2-chloroacetamide derivatives as prospective antimicrobial and antiproliferative agents

To combat the antimicrobial and anticancer drug resistance by pathogens and cancerous cells, efforts has been made to study the pharmacological activities of newly synthesized N-(4-(4-bromophenyl)thiazol-2-yl)-2-chloroacetamide derivatives. The molecular structures of the synthesized derivatives were confirmed by their physicochemical properties and spectroanalytical data (NMR, IR and elemental). The synthesized compounds were evaluated for their in vitro antimicrobial activity against bacterial (Gram positive and Gram negative) and fungal species using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. Molecular docking studies were carried out to study the binding mode of active compounds with receptor using Schrodinger v11.5. The antimicrobial activity results revealed that compounds d1, d2 and d3 have promising antimicrobial activity. Anticancer screening results indicated that compounds d6 and d7 were found to be the most active ones against breast cancer cell line. Furthermore, the molecular docking study demonstrated that compounds d1, d2, d3, d6 and d7 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and has the potential to be used as lead compounds for rational drug designing.

Sensitizing Prostate Cancer Cells to IL‐27 Immunotherapy by Chemotherapy Induced Immunogenic Modulation

Bone‐metastasis occurs in most patients suffering from advanced prostate cancer. Treatment options for such patients are currently limited and immunogenic modulation (IMO) is emerging as a possible therapeutic option. IMO involves changes in cancer cell‐phenotype in response to treatment with sub‐clinical doses of chemotherapy which makes cells more susceptible to an immune attack. By utilizing the immune system to eliminate tumors, one can effectively reduce chemotherapy toxicity and the associated side‐effects. Moreover, an IMO approach may enable one to treat tumors unresponsive or resistant to chemotherapy. Our goal for this project is to characterize and optimize the response of prostate cancer cells to sub‐lethal doses of chemotherapy drugs. We examined gene expression changes in cancer cells in vitro following exposure to varying sub‐lethal concentrations of chemotherapeutics and optimized cellular response with respect to the duration of treatment, drug concentrations, and different cell types by using quantitative Polymerase Chain Reaction (qPCR), viability assays, and flow cytometry approaches. Expression levels of five markers of IMO were investigated in two prostate cancer cell lines. For example, the carcinoembryonic (CEA) gene, which is a tumor antigen and previously associated with IMO, was significantly upregulated in response to sublethal doses of chemotherapy and thus was selected for subsequent characterization. Of the five drugs that we tested across two cell lines, Cabozantinib and Docetaxel showed the most promising response in upregulating CEA. PC3 cells (a human prostate cancer adenocarcinoma cell line) showed a ~15‐fold change in CEA expression 48 h post‐docetaxel treatment. Similarly, Cabozantinib promoted a ~11‐fold CEA upregulation after 72 h of treatment. These gene expression changes were confirmed using flow cytometry. These results suggest that sub‐lethal doses of chemotherapy might induce tumor cell sensitivity to CEA‐specific T‐cell mediated killing. Further studies in in vivo models to profile tumor‐infiltrating immune effectors will help characterize the associated immune response and examine whether chemotherapy and immunotherapy (IL‐27) can act in synergy to enhance the anti‐tumor immune response. We anticipate that such combinational therapy will open new avenues for treating bone‐metastatic prostate cancer while reducing chemotherapy‐associated toxicity.Support or Funding InformationNIH NCI R01CA196947This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Morphological characteristics of vasculogenic mimicry and its correlation with EphA2 expression in gastric adenocarcinoma

Genetically deregulated tumor cells generate vascular channels by vasculogenic mimicry (VM) that is independent of endothelial blood vessels. The morphological characteristics of VM and the role of EphA2 in the formation of VM were evaluated in 144 clinical samples of gastric adenocarcinoma and AGS gastric cancer cell line. It has long been believed that VM consists of PAS-positive basement membrane and CD31/CD34-negative cells. Interestingly, we found that the luminal surface of gastric tumor cells that form VM channels showed PAS-positive reaction, and that the involvement of CD31/CD34-positive tumor cells in the formation of VM channels. Highly aggressive tumor cells that formed VM were found to express CD31 or CD34, implicating the angiogenic and vasculogenic potential of the genetically deregulated tumor cells. VM occurrence was positively correlated with high expression of EphA2 in our patient cohort, and the indispensable role of EphA2 in VM formation was identified by gene silencing in AGS cells. We also report that Epstein–Barr virus (EBV)-positive tumor cells were involved in the formation of VM channels in EBV-associated gastric cancer samples. Overall, our results suggest that EphA2 signaling promotes tumor metastasis by inducing VM formation during gastric tumorigenesis.

Pyrrolizines as Potential Anticancer Agents: Design, Synthesis, Caspase-3 activation and Micronucleus (MN) Induction.

For further exploration of the promising pyrrolizine scaffold and in continuation of our previous work, that proved the potential anticancer activity of the hit compound I, a new series of pyrrolizines 2-5 and 7-9 were designed and synthesized. Structures of the new compounds were confirmed by IR, 1H-NMR, 13C-NMR and elemental analysis. Antitumor activity for the prepared compounds against human breast adenocarcinoma (MCF-7), liver (HEPG2) and colon (HCT116) cancer cell lines was evaluated using SRB assay method. Compounds 2, 3 and 5 were the most potent on colon cancer cells, their IC50 values were less than 5 µM. Compounds 2, 3 and 8 were the most potent on liver cancer cells, their IC50 values were less than 10 µM. As for MCF7, compounds 2, 7, 8 and 9 were the most active with IC50 values less than 10 µM. We can conclude that combining pyrrolizine scaffold with urea gave abroad spectrum anticancer agent 2 against the three tested cell lines. Micronucleus assays showed that compounds 2, 3, 8 are mutagenic and can induce apoptosis. In addition, caspase-3 activation was evaluated and compound 2 showed increase in the level of caspase-3 (9 folds) followed by 3 (8.28 folds) then 8 (7.89 folds). The obtained results encourage considering these three compounds as novel anticancer prototypes.

HPLC Analysis of Phenolic Acids, Antioxidant Activity and in vitro Effectiveness of Green and Roasted Caffea arabica Bean Extracts: A Comparative Study.

Coffee is a popular drink; it is one of the most commercialized food products and a rich source of biologically active compounds that are important for human health. This study aimed to prove the anticancer activity of Green Coffee (GC) and Roasted Coffee (RC) bean aqueous extracts (Coffea arabica) on breast cancer adenocarcinoma cell line (MCF-7) and the safety of both extracts on normal Human Peripheral Blood Lymphocytes culture (HPBL). Total phenolic content for GC and RC extracts was measured and result of both extracts were (0.308±0.016 & 0.233±0.013mg/g) respectively. The phenolic acids were screened by HPLC at the wavelength of 254& 278 and 300 nm and 5-caffeoylquinic acids (Chlorogenic acid), the predominant form of phenolic acids, was identified in GC and RC samples. Ferric Reducing Antioxidant Power (FRAP) as well as the free radical scavenging activity (DPPH) proved the antioxidant properties of both extracts. The DPPH IC50 mean values of GC and RC extracts were (2.4±0.08, 2.3±0.16 µg/ml) respectively. Cytotoxicity of both extracts on MCF-7 cells were evaluated by neutral red uptake assay which showed the IC50 mean values (377±5.7,500±8.1 µg/ml) for GC and RC extracts respectively. The safety of both extracts (0, 125, 250, 500 µg/ml) on HPBL was evaluated in vitro using trypan blue exclusion method and DNA single strand breaks (alkaline comet assay). Result revealed non-significant cytotoxic difference (P<0.001) between cultures especially at lower doses of GC and RC extracts except the highest dose of GC and RC extract which showed slightly significant damage (P<0.001). This study proved that GC and RC aqueous extracts were found to be selectively cytotoxic in vitro to cancerous cells (MCF-7 cell line) causing cell death with no cytotoxicity on normal human lymphocytes especially at lower doses.

In vitro cytotoxic activity of Zaleya Pentandra L. Extracts against the breast cancer adenocarcinoma cell line MCF-7.

To evaluate the cytotoxicity of crude aqueous and ethanol extracts of Zaleya pentandra against oestrogen receptor-positive breast cancer cell line Michigan Cancer Foundation-7. The study was conducted at the Institute of Chinese Medicine, the Chinese University of Hong Kong, Hong Kong, from March to September 2017, and comprised Zaleya pentandra herbaceous perennial plant collected from Pakistani cities of Shakargarh, Lahore and Sialkot. Both aqueous and ethanol extracts were prepared in solvents following Soxhlet extraction technique. Rate of reduction in viability of cancer cell line was studied through MTT (dye compound 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) assay on the basis of time of incubation and the dose of extract. Analysis was performed using High Performance Liquid Chromatography with Diode Array Detector in order to found the compounds responsible for the death of cancer cells. Cell viability was observed to be dose-dependent (range: 16.7-37.4%) for aqueous extracts. Minimum inhibition concentration was 16.65% at 200μg/ml after 24 hours of incubation, whereas maximum inhibition was 37.39% at 3200μg/ml. Ethanol extracts showed less inhibition, with maximum inhibition being 25.29% at 1000μg/ml and minimum 13.57% at 62.5μg/ml. Certain polar compounds, like Hydroxytrosol and Tyrosol, could be obtained from the aqueous extracts only. Zaleya pentandra aqueous extract was found to have potential benefit towards cytotoxicity of breast cancer cells.

Synthesis, docking, and cytotoxic activities of novel 2-aryl-4-(arylamino)quinazolines

A synthesis of functionalized 2-aryl-4-(arylamino)quinazolines from 4-chloro-2-arylquinazolines (derived from 2-arylquinazolin-4(3H)-one) and 5-chloroaniline derivatives in DMF is described. The interaction of 2-aryl-4-(arylamino)quinazolines with their biological target, human epithelial growth factor receptor (EGFR), was investigated by molecular docking. Docking results indicated lower binding energy for all compounds towards EGFR active sites. The cytotoxic activities of fifteen 2-aryl-4-(arylamino)quinazolines are evaluated against lung adenocarcinoma (A549) and ovarian cancer (SKOV3) cell lines using MTT method. Our results demonstrated that among the tested compounds 2-(4-bromophenyl)-N-(5-chloro-2-methylphenyl)quinazolin-4-amine and N-(2,5-dichlorophenyl)-2-(4-chlorophenyl)quinazolin-4-amine showed desirable cytotoxic activities on both cell lines. Compounds 2-(3-bromophenyl)-N-(5-chloro-2-methylphenyl)quinazolin-4-amine and 2-(4-bromophenyl)-N-(2,5-dichlorophenyl)quinazolin-4-amine displayed appropriate cytotoxic activities on A549 and SKOV3 cell lines, respectively.

93P - Decreasing telomerase activity of adenocarcinoma cancer cell line (AGS) is associated with different concentrations of sodium selenite and cadmium chloride and selenium l methionine

93P - Decreasing telomerase activity of adenocarcinoma cancer cell line (AGS) is associated with different concentrations of sodium selenite and cadmium chloride and selenium l methionine

E-Cadherin Loss Accelerates Tumor Progression and Metastasis in a Mouse Model of Lung Adenocarcinoma.

Metastatic disease is the primary cause of death of patients with lung cancer, but the mouse models of lung adenocarcinoma do not accurately recapitulate the tumor microenvironment or metastatic disease observed in patients. In this study, we conditionally deleted E-cadherin in an autochthonous lung adenocarcinoma mouse model driven by activated oncogenic Kras and p53 loss. Loss of E-cadherin significantly accelerated lung adenocarcinoma progression and decreased survival of the mice. Kras;p53;E-cadherin mice had a 41% lung tumor burden, invasive grade 4 tumors, and a desmoplastic stroma just 8 weeks after tumor initiation. One hundred percent of the mice developed local metastases to the lymph nodes or chest wall, and 38% developed distant metastases to the liver or kidney. Lung adenocarcinoma cancer cell lines derived from these tumors also had high migratory rates. These studies demonstrate that the Kras;p53;E-cadherin mouse model better emulates the tumor microenvironment and metastases observed in patients with lung adenocarcinoma than previous models and may therefore be useful for studying metastasis and testing new lung cancer treatments in vivo.

Texture feature extraction of gray-level co-occurrence matrix for metastatic cancer cells using scanned laser pico-projection images.

Metastasis is responsible for 90% of all cancer-related deaths in humans, and the development of a rapid and promising solution for an early diagnosis of metastasis is required. The present study proposed a promising method combined with scanned laser pico-projection technique and typical texture feature (i.e., contrast, correlation, energy, entropy, and homogeneity) extraction of gray-level co-occurrence matrix (GLCM) image processing model to classify the low- and high-metastatic cancer cells using five common cancer adenocarcinoma cell line pairs (i.e., HeLa/HeLa-S3, CL1-0/CL1-5, OVTW59-P0/OVTW59-P4, and CE81T-FNlow/CE81T-FNhigh cell lines). Highly metastatic cancer cells essentially have the highest levels of disorder. Both contrast and entropy refer to the degree of disorder, and energy and homogeneity refer to the degree of uniformity. These four texture features can be effective evaluation indexes for disorder in cancer cells responding to metastatic ability. Texture feature extraction forms reflection images, which are recorded with scanned laser pico-projection system; they effectively bridge the gap in information derived from transmission images. The low- and high-metastatic cancer cells are statistically and effectively classified from the texture feature of GLCM through transmission and reflection images taken with scanned laser pico-projection system. In particular, it only requires several seconds after producing a confluent monolayer of cells and achieves the rapid method with a more reliable diagnostic performance for metastatic ability of cancer cells in vitro or ex vivo.

Poly Organotin Acetates against DNA with Possible Implementation on Human Breast Cancer.

Two known tin-based polymers of formula {[R3Sn(CH3COO)]n} where R = n-Bu– (1) and R = Ph– (2),were evaluated for their in vitro biological properties. The compounds were characterized via their physical properties and FT-IR, 119Sn Mössbauer, and 1H NMR spectroscopic data. The molecular structures were confirmed by single-crystal X-Ray diffraction crystallography. The geometry around the tin(IV) ion is trigonal bi-pyramidal. Variations in O–Sn–O···Sn′ torsion angles lead to zig-zag and helical supramolecular assemblies for 1 and 2, respectively. The in vitro cell viability against human breast adenocarcinoma cancer cell lines: MCF-7 positive to estrogens receptors (ERs) and MDA-MB-231 negative to ERs upon their incubation with 1 and 2 was investigated. Their toxicity has been studied against normal human fetal lung fibroblast cells (MRC-5). Compounds 1 and 2 exhibit 134 and 223-fold respectively stronger antiproliferative activity against MDA-MB-231 than cisplatin. The type of the cell death caused by 1 or 2 was also determined using flow cytometry assay. The binding affinity of 1 and 2 towards the CT-DNA was suspected from the differentiation of the viscosity which occurred in the solution containing increasing amounts of 1 and 2. Changes in fluorescent emission light of Ethidium bromide (EB) in the presence of DNA confirmed the intercalation mode of interactions into DNA of both complexes 1 and 2 which have been ascertained from viscosity measurements. The corresponding apparent binding constants (Kapp) of 1 and 2 towards CT-DNA calculated through fluorescence spectra are 4.9 × 104 (1) and 7.3 × 104 (2) M−1 respectively. Finally, the type of DNA binding interactions with 1 and 2 was confirmed by docking studies.

Abstract 5842: Oxidative stress and protein carbonylation towards multi-drug resistance in cancer

Abstract Reactive oxygen species (ROS) are constantly produced under normal as well as stress conditions and play important roles in cell signaling and homeostasis. An elevated level of ROS has been reported in most cancers which may play a critical role in both cancer progression or cancer suppression. One proposed therapeutic strategy is to alter the oxidative stress from ROS-induced tumor promoting event to a ROS-induced apoptotic signaling. Most ROS inducing therapeutic agents initially induce ROS to kill cancer cells by apoptosis; however, prolonged exposure of drugs may result in reduced ROS level and an adaptive microenvironment that makes cancer cells resistant to the same ROS-inducing therapeutic drugs. Chronic exposure of ROS may also upregulate the multidrug resistance protein expression in cancer cells. We hypothesize that differences in oxidative stress and the antioxidant response between drug sensitive and drug resistance cells may play a key role in drug resistance to redox-active drugs. We used two pairs of cell lines, a mitoxantrone sensitive and resistance MCF7 human breast adenocarcinoma (MCF7/MCF7MX) and H460 non-small lung cancer cell lines (H460/H460MX) for our experiments. We employed western blot and ELISA assays to determine the total and specific protein oxidation by carbonylation. Both MCF7MX and H460MX showed slightly lower level of total protein carbonylation compared to their mitoxantrone sensitive counterparts. In western blot analysis, we observed two specific proteins that were differentially carbonylated in MCF7MX compared to and MCF7. Both cytoskeletal and multifunctional proteins were identified by mass spectrometry and confirmed by two-color western blot analysis. Investigation of the potential roles of these specific protein carbonylation in drug resistance will be presented. Citation Format: Baikuntha P. Aryal, Jean-Pierre Gillet, V Ashutosh Rao. Oxidative stress and protein carbonylation towards multi-drug resistance in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5842.