scholarly journals Salinomycin Treatment Specifically Inhibits Cell Proliferation of Cancer Stem Cells Revealed by Longitudinal Single Cell Tracking in Combination with Fluorescence Microscopy

2020 ◽  
Vol 10 (14) ◽  
pp. 4732
Author(s):  
Sofia Kamlund ◽  
Birgit Janicke ◽  
Kersti Alm ◽  
Stina Oredsson
Keyword(s):  
Cell Proliferation ◽  
Fluorescence Microscopy ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Digital Holography ◽  
Cell Tracking ◽  
Population Based ◽  
Longitudinal Tracking ◽  
Long Time ◽  
New Anticancer Drugs

A cell line derived from a tumor is a heterogeneous mixture of phenotypically different cells. Such cancer cell lines are used extensively in the search for new anticancer drugs and for investigating their mechanisms of action. Most studies today are population-based, implying that small subpopulations of cells, reacting differently to the potential drug go undetected. This is a problem specifically related to the most aggressive single cancer cells in a tumor as they appear to be insensitive to the drugs used today. These cells are not detected in population-based studies when developing new anticancer drugs. Thus, to get a deeper understanding of how all individual cancer cells react to chemotherapeutic drugs, longitudinal tracking of individual cells is needed. Here we have used digital holography for long time imaging and longitudinal tracking of individual JIMT-1 breast cancer cells. To gain further knowledge about the tracked cells, we combined digital holography with fluorescence microscopy. We grouped the JIMT-1 cells into different subpopulations based on expression of CD24 and E-cadherin and analyzed cell proliferation and cell migration for 72 h. We investigated how the cancer stem cell (CSC) targeting drug salinomycin affected the different subpopulations. By uniquely combining digital holography with fluorescence microscopy we show that salinomycin specifically targeted the CD24− subpopulation, i.e., the CSCs, by inhibiting cell proliferation, which was evident already after 24 h of drug treatment. We further found that after salinomycin treatment, the surviving cells were more epithelial-like due to the selection of the CD24+ cells.

scholarly journals Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing Platform

2021 ◽  
Vol 23 (1) ◽  
pp. 122
Author(s):  
Dongwei Wu ◽  
Johanna Berg ◽  
Birte Arlt ◽  
Viola Röhrs ◽  
Munir A. Al-Zeer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Human Cancer ◽  
Early Death ◽  
Human Kidney ◽  
Therapeutic Window ◽  
Cancer Model ◽  
Cell Type ◽  
Anaplastic Lymphoma ◽  
New Anticancer Drugs

Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type.

scholarly journals Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 747
Author(s):  
Eleonora Turrini ◽  
Piero Sestili ◽  
Carmela Fimognari
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Bioactive Molecules ◽  
Piper Nigrum ◽  
Comprehensive Overview ◽  
Anticancer Properties ◽  
Toxicological Profile ◽  
Key Pathways ◽  
New Anticancer Drugs

The main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient’s quality of life. Therefore, the discovery of new anticancer drugs remains an urgent challenge. Natural products represent an excellent opportunity due to their ability to target heterogenous populations of cancer cells and regulate several key pathways involved in cancer development, and their favorable toxicological profile. Piper nigrum is one of the most popular spices in the world, with growing fame as a source of bioactive molecules with pharmacological properties. The present review aims to provide a comprehensive overview of the anticancer potential of Piper nigrum and its major active constituents—not limited to the well-known piperine—whose undeniable anticancer properties have been reported for different cancer cell lines and animal models. Moreover, the chemosensitizing effects of Piper nigrum in association with traditional anticancer drugs are depicted and its toxicological profile is outlined. Despite the promising results, human studies are missing, which are crucial for supporting the efficacy and safety of Piper nigrum and its single components in cancer patients.

Risk of Incremental Toxicities and Associated Costs of New Anticancer Drugs: A Meta-Analysis

2014 ◽  
Vol 32 (32) ◽  
pp. 3634-3642 ◽  
Author(s):  
Saroj Niraula ◽  
Eitan Amir ◽  
Francisco Vera-Badillo ◽  
Bostjan Seruga ◽  
Alberto Ocana ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Meta Analysis ◽  
Molecular Target ◽  
Chemotherapeutic Agents ◽  
Targeted Agents ◽  
Treatment Frequency ◽  
Experimental Drugs ◽  
Grade 3 ◽  
New Anticancer Drugs

Purpose There are increasing reports of rare but serious toxicities caused by new anticancer drugs, and there are costs associated with their management. Methods We identified anticancer drugs approved by the US Food and Drug Administration from 2000 to 2011 and pivotal trials supporting their registration. Twelve frequent grade 3 to 4 adverse event (AEs) were weighted and pooled in a meta-analysis. Estimates of incremental drug prices and incremental costs for management of AEs were calculated according to type of new agent based on target specificity. Results We identified 41 studies comprising 27,539 patients and evaluating 19 experimental drugs. Agents directed against a specific molecular target on cancer cells had a lower incidence of grade 3 to 4 toxicities compared with controls (median risk ratio [RR], 0.67; P = .22), whereas less-specific targeted agents, including angiogenesis inhibitors (median RR, 3.39; P < .001) and chemotherapeutic agents (median RR, 1.73; P < .001), were more toxic. Risk was increased regardless of whether the control arm contained active treatment (RR, 2.11; P < .001) or not (RR, 3.02; P < .001). Median incremental drug price for experimental agents was $6,000 per patient per month. Median cost of managing toxicity was low compared with drug costs but higher than controls for treatment with less-specific targeted agents and chemotherapies. Conclusion Newly approved anticancer drugs are associated with increased toxicity, except for agents with a specific molecular target on cancer cells. Management of toxicity leads to a small increase in overall cost of treatment. Frequency of toxicity and associated costs are likely higher in less-selected patients treated in general oncologic practice. Development of biomarker-driven agents should be encouraged.

Cytotoxic Effect of the Combination of Gemcitabine and Atorvastatin Loaded in Microemulsion on the HCT116 Colon Cancer Cells

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Mayson H. Alkhatib ◽  
Dalal Al-Saedi ◽  
Wadiah S. Backer
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Therapeutic Potential ◽  
Morphological Changes ◽  
In Vitro Study ◽  
Colon Cancer Cells ◽  
Apoptosis Detection ◽  
Hct116 Cells

The combination of anticancer drugs in nanoparticles has great potential as a promising strategy to maximize efficacies by eradicating resistant, reduce the dosage of the drug and minimize toxicities on the normal cells. Gemcitabine (GEM), a nucleoside analogue, and atorvastatin (ATV), a cholesterol lowering agent, have shown anticancer effect with some limitations. The objective of this in vitro study was to evaluate the antitumor activity of the combination therapy of GEM and ATVencapsulated in a microemulsion (ME) formulation in the HCT116 colon cancer cells. The cytotoxicity and efficacy of the formulation were assessed by the 3- (4,5dimethylthiazole-2-yl)-2,5-diphyneltetrazolium bromide (MTT) assay. The mechanism of cell death was examined by observing the morphological changes of treated cells under light microscope, identifying apoptosis by using the ApopNexin apoptosis detection kit, and viewing the morphological changes in the chromatin structure stained with 4′,6-diamidino-2-phenylindole (DAPI) under the inverted fluorescence microscope. It has been found that reducing the concentration of GEM loaded on ME (GEM-ME) from 5μM to 1.67μM by combining it with 3.33μM of ATV in a ME formulation (GEM/2ATV-ME) has preserved the strong cytotoxicity of GEM-ME against HCT116 cells. The current study proved that formulating GEM with ATV in ME has improved the therapeutic potential of GEM and ATV as anticancer drugs.

Oncogenic LncRNA CASC9 in Cancer Progression

2020 ◽  
Vol 26 ◽  
Author(s):  
Yuying Qi ◽  
Chaoying Song ◽  
Jiali Zhang ◽  
Chong Guo ◽  
Chengfu Yuan
Keyword(s):  
Cell Proliferation ◽  
Drug Resistance ◽  
Cell Growth ◽  
Cancer Cells ◽  
Therapeutic Potential ◽  
Squamous Metaplasia ◽  
Neoplastic Transformation ◽  
Over Expression ◽  
Human Cancers ◽  
Current Review

Background: Long non-coding RNA (LncRNAs), with the length over 200 nucleotides, originate from intergenic, antisense, or promoter-proximal regions, is a large family of RNAs that lack coding capacity. Emerging evidences illustrated that LncRNAs played significant roles in a variety of cellular functions and biological processes in profuse human diseases, especially in cancers. Cancer susceptibility candidate 9 (CASC9), as a member of the LncRNAs group, was firstly found its oncogenic function in esophageal cancer. In following recent studies, a growing amount of human malignancies are verified to be correlated with CASC9, most of which are derived from the squamous epithelium tissue. This present review attempts to highlight the latest insights into the expression, functional roles, and molecular mechanisms of CASC9 in different human malignancies. Methods: In this review, the latest findings related to the pathophysiological processes of CASC9 in human cancers were summarized and analyzed, the associated studies were collected in systematically retrieval of PubMed used lncRNA and CASA9 as keywords. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depress cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 closely relates to neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of CASC9 in various human cancers. Results: CASC9 expression is identified to be aberrantly elevated in a variety of malignancies. The over-expression of CASC9 has been suggested to accelerate cell proliferation, migration, cell growth and drug resistance of cancer cells, while depress cell apoptosis, revealing its role as an oncogene. Moreover, the current review demonstrated CASC9 closely relates to neoplastic transformation of squamous epithelial cells and squamous metaplasia in non-squamous epithelial tissues. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of CASC9 in various human cancers. Conclusion: Long non-coding RNACASC9 likely served as useful disease biomarkers or therapy targets that could effectively apply in treatment of different kinds of cancers.

Panax Notoginseng Saponins Promote Cell Death and Chemosensitivity in Pancreatic Cancer through the Apoptosis and Autophagy Pathways

2020 ◽  
Vol 20 ◽  
Author(s):  
Li-Chao Yao ◽  
Lun Wu ◽  
Wei Wang ◽  
Lu-Lu Zhai ◽  
Lin Ye ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Panax Notoginseng ◽  
Panax Notoginseng Saponins ◽  
Transwell Assay ◽  
Pancreatic Cancer Cells ◽  
New Strategy ◽  
Induced Apoptosis ◽  
Promote Cell Death

Background:: Panax Notoginseng Saponins (PNS) is used as traditional Chinese medicine for ischemic stroke and cardiovascular disease, it has been proven to possess anticancer activity recently. Objective:: In this study, we aimed to explore the anticancer curative effect and potential mechanisms of PNS in pancreatic cancer cells. Methods:: Pancreatic cancer Miapaca2 and PANC-1 cells were treated with PNS and Gemcitabine (Gem), respectively. Then the cell viability was assessed by CCK-8 assay, cell proliferation was tested by colony formation assay and EdU cell proliferation assay, cell migration and invasiveness were tested by wound healing assay and transwell assay respectively, and cell apoptosis was detected by flow cytometry. Finally, we detected the expression levels of proteins related to migration, apoptosis and autophagy through Western blotting. Results:: PNS not only inhibited the proliferation, migration, invasion and autophagy of Miapaca2 and PANC-1 cells, but also induced apoptosis and promoted chemosensitivity of pancreatic cancer cells to Gem. Conclusion:: PNS may exhibit cytotoxicity and increase chemosensitivity of pancreatic cancer cells to Gem by inhibiting autophagy and inducing apoptosis, providing a new strategy and potential treatment option for pancreatic cancer.

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