Anticancer siRNA cocktails as a novel tool to treat cancer cells. Part (B). Efficiency of pharmacological action

Abstract Muscle fructose-1,6-bisphosphate aldolase (ALDOA) is among the most abundant glycolytic enzymes in all cancer cells. Here, we show that the enzyme plays a previously unknown and critical role in a cancer cell survival. Simultaneous inhibition of ALDOA activity and interaction with F-actin cytoskeleton using ALDOA slow-binding inhibitor UM0112176 leads to a rapid cofilin-dependent loss of F-actin stress fibers which is associated with elevated ROS production, inhibition of ATP synthesis, increase in calcium levels, caspase activation and arrested cellular proliferation. These effects can be reproduced by silencing of ALDOA. The mechanism of pharmacological action is, however, independent of the catalytic function of the enzyme, specific to cancer cells, and is most deleterious to cells undergoing the epithelial–mesenchymal transition, a process facilitating cancer cell invasion. Our results demonstrate that the overabundance of ALDOA in cancer cells is associated with its moonlighting rather than catalytic functions. This may have significant implications for development of novel broad-based anti-cancer therapies.

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Parthenolide Induces Reactive Oxygen Species-Mediated Autophagic Cell Death in Human Osteosarcoma Cells

Cellular Physiology and Biochemistry ◽

10.1159/000452532 ◽

2016 ◽

Vol 40 (1-2) ◽

pp. 146-154 ◽

Cited By ~ 8

Author(s):

Chen Yang ◽

Qing Ou Yang ◽

Qing-Jie Kong ◽

Wen Yuan ◽

Yue-Ping Ou Yang

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Cancer Cells ◽

Reactive Oxygen ◽

Annexin V ◽

Pharmacological Action ◽

Autophagic Cell Death ◽

Oxygen Species ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells

Background and Aim: Osteosarcoma is a devastating tumor of bone, primarily affecting adolescents. Parthenolide, a naturally occurring small molecule that interferes with NF-κB signaling, has recently attracted considerable attention because of its pharmacological action involving anti-cancer effects. However, the mechanism of the cytotoxic effect exerted by parthenolide on tumor cells is not clearly defined today. Methods: In this study, the effects of parthenolide were evaluated and characterized in human osteosarcoma cancer cell. Cell viability was assessed by CCK-8. Apoptosis was assessed by Annexin V-FITC/PI Flow cytometry assay. Relative quantitative real-time PCR and western blot were used to determine the expressions of genes and proteins. Results: Our results suggest that parthenolide did not cause caspase-dependent cell death in osteosarcoma cancer cells, as indicated by the absence of significant early apoptosis as well as caspase-3 cleavage. Instead, parthenolide increased the autophagy and mitophagy, as characterized by increased PINK1 and Parkin translocation to mitochondria and enhanced autophagy proteins. The induction of autophagy by parthenolide was associated with the increase of reactive oxygen species (ROS). ROS antioxidants N-acetylcysteine (NAC) attenuated parthenolide-induced autophagy activity. Conclusions: Our findings unveil a novel mechanism of drug action by parthenolide in osteosarcoma cancer cells and suggest a potential value of treating osteosarcoma cancer through a caspase-independent autophagic cell death by ROS activation.

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Pharmacological Action and Changes of Gene Expression by Cannabidiol Treatment in Human Dermal Papilla Cells and A549 Lung Cancer Cells

10.26226/morressier.60dc99f4e537565438d6c0c1 ◽

2021 ◽

Author(s):

Keun-Cheol Kim

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Cancer Cells ◽

Dermal Papilla ◽

Pharmacological Action ◽

Lung Cancer Cells ◽

Dermal Papilla Cells ◽

A549 Lung

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Ultrastructural modification of cellular interactions in cancer tumor

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100082455 ◽

1978 ◽

Vol 36 (2) ◽

pp. 318-319

Author(s):

N. P. Dmitrieva

Keyword(s):

Cancer Cells ◽

Human Thyroid ◽

Adjacent Cell ◽

Main Role ◽

Cellular Interactions ◽

Electron Microscopic ◽

Cancer Tumor ◽

Normal Human ◽

Characteristic Features

One of the most characteristic features of cancer cells is their ability to metastasia. It is suggested that the modifications of the structure and properties of cancer cells surfaces play the main role in this process. The present work was aimed at finding out what ultrastructural features apear in tumor in vivo which removal of individual cancer cells from the cell population can provide. For this purpose the cellular interactions in the normal human thyroid and cancer tumor of this gland electron microscopic were studied. The tissues were fixed in osmium tetroxide and were embedded in Araldite-Epon.In normal human thyroid the most common type of intercellular contacts was represented by simple junction formed by the parallelalignment of adjacent cell membranees leaving in between an intermembranes space 15-20 nm filled with electronlucid material (Fig. 1a). Sometimes in the basal part of cells dilatations of the intercellular space 40-50 nm wide were found (Fig. 1a). Here the cell surfaces may form single short microvilli.

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Ultrastructural Localization Study of Carcinoembryonic Antigen (CEA) in Gastric Cancer: Immunoelectron Microscopic Observation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158807 ◽

1990 ◽

Vol 48 (3) ◽

pp. 252-253

Author(s):

Dong Yuming ◽

Yang Guanglin ◽

Wu Jifeng ◽

Chen Xiaolin

Keyword(s):

Gastric Cancer ◽

Intestinal Metaplasia ◽

Cancer Cells ◽

Microscopic Observation ◽

Biological Significance ◽

Ultrastructural Localization ◽

Mucinous Carcinoma ◽

Surface Glycoprotein ◽

Tubular Adenocarcinoma ◽

Pap Method

On the basis of light microscopic observation, the ultrastructural localization of CEA in gastric cancer was studied by immunoelectron microscopic technique. The distribution of CEA in gastric cancer and its biological significance and the mechanism of abnormal distribution of CEA were further discussed.Among 104 surgically resected specimens of gastric cancer with PAP method at light microscopic level, the incidence of CEA(+) was 85.58%. All of mucinous carcinoma exhibited CEA(+). In tubular adenocarcinoma the incidence of CEA(+) showed a tendency to rising with the increase of degree of differentiation. In normal epithelia and intestinal metaplasia CEA was faintly present and was found only in the luminal surface. The CEA staining patterns in cancer cells were of three types--- cytoplasmic, membranous and weak reactive type. The ultrastructural localization of CEA in 14 cases of gastric cancer was studied by immunoelectron microscopic technique.There was a little or no CEA in the microvilli of normal epithelia. In intestinal metaplasia CEA was found on the microvilli of absorptive cells and among the mucus particles of goblet cells. In gastric cancer CEA was also distributed on the lateral and basal surface or even over the entire surface of cancer cells and lost their polarity completely. Many studies had proved that the alterations in surface glycoprotein were characteristic changes of tumor cells. The antigenic determinant of CEA was glycoprotein, so the alterations of tumor-associated surface glycoprotein opened up a new way for the diagnosis of tumors.

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Water-soluble amphiphilic ruthenium(ii) polypyridyl complexes as potential light-activated therapeutic agents

Chemical Communications ◽

10.1039/d0cc04397d ◽

2020 ◽

Vol 56 (65) ◽

pp. 9332-9335

Author(s):

Sandra Estalayo-Adrián ◽

Salvador Blasco ◽

Sandra A. Bright ◽

Gavin J. McManus ◽

Guillermo Orellana ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Cellular Uptake ◽

Therapeutic Agents ◽

Water Soluble ◽

Polypyridyl Complexes ◽

Cervical Cancer Cells

Two new water-soluble amphiphilic Ru(ii) polypyridyl complexes were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and phototoxicity against HeLa cervical cancer cells.

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