Locomotion of Cancer Cells in vivo Compared with Normal Cells

1967 ◽  
pp. 26-30 ◽  
Author(s):  
Sumner Wood ◽  
R. Robinson Baker ◽  
Barbara Marzocchi
Keyword(s):  
Cancer Cells ◽  
Normal Cells

Innovative dual system for selective eradication of cancer cells using exosomes carrying natural bacterial toxin-antitoxin (TA).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14635-e14635
Author(s):  
Shiran Shapira ◽  
Ilana Boustanai ◽  
Dina Kazanov ◽  
Ahmad Fokra ◽  
Ezra Bernstein ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Xenograft Model ◽  
Genetic Alterations ◽  
Bacterial Toxin ◽  
Genetic Profile ◽  
Dependent Manner ◽  
Normal Cells ◽  
Responsive Element

e14635 Background: Inactivation of P53 and activation of ras are frequent genetic alterations in cancer. We have shown in vitro and in vivo, that the TA system can selectively and effectively eradicate RAS-mutated cancer cells. Aim: Selective killing of cancer cells while sparing the normal cells based on tumor genetic signature. Methods: A “first generation” ΔE1/ΔE3 human type-5 adenoviral-vectors for gene delivery were designed and constructed to specifically target cancer cells. They are designated as "PY4-mazF-mCherry" (PY4, ras responsive element), "ΔPY4-mazF-mCherry" (control viruses) and "RGC-mazE-IRES-GFP" (RGC, P53 responsive element). Their potency was tested in vitro, by the enzymatic MTT assay, microscopic observation, colony formation assay and FACS analysis, and in a xenograft model of CRC. Next, we generated, small natural vesicles, exosomes, that directly targeted cancer through specific small antibody fragments against CD24 that is expressed in most cancer cells and rarely on normal cells. Results: The TA system ("PY4-mazF-mCherry"+"RGC-mazE-IRES-GFP") induced a massive cell death, in a dose-dependent manner in vitro, 69% as compared to 19% in control co-infected ("ΔPY4-mazF-mCherry"+"RGC-mazE-IRES-GFP") HCT116 CRC cells (mutated RAS and p53). In vivo, growth of HCT116-/- ( KRASmutand P53mut) and HCT116+/+ ( KRASmut and P53wt) tumors were significantly inhibited (70% and 65%, respectively). Conclusions: 1. Abusing the P53 genetic status and the activated Ras pathway holds promising effective and safe strategy to target tumor cells while sparing normal tissues. 2. It is a proof of concept for personalized cancer therapy based on the tumor genetic profile.

Cancer Targeted Nanoparticles Specifically Induce Apoptosis in Cancer Cells and Spare Normal Cells

2012 ◽  
Vol 65 (1) ◽  
pp. 5 ◽  
Author(s):  
Jagat R. Kanwar ◽  
Rupinder K. Kanwar ◽  
Ganesh Mahidhara ◽  
Chun Hei Antonio Cheung
Keyword(s):  
Adverse Effects ◽  
Cancer Cells ◽  
Modern Medicine ◽  
Chemotherapeutic Agents ◽  
Locked Nucleic Acid ◽  
Cancer Drug ◽  
Drug Induced ◽  
Normal Cells

Curing cancer is the greatest challenge for modern medicine and finding ways to minimize the adverse effects caused by chemotherapeutic agents is of importance in improving patient’s physical conditions. Traditionally, chemotherapy can induce various adverse effects, and these effects are mostly caused by the non-target specific properties of the chemotherapeutic compounds. Recently, the use of nanoparticles has been found to be capable of minimizing these drug-induced adverse effects in animals and in patients during cancer treatment. The use of nanoparticles allows various chemotherapeutic drugs to be targeted to cancer cells with lower dosages. In addition to this, the use of nanoparticles also allows various drugs to be administered to the subjects by an oral route. Here, locked nucleic acid (LNA)-modified epithelial cell adhesion molecules (EpCAM), aptamers (RNA nucleotide), and nucleolin (DNA nucleotide) aptamers have been developed and conjugated on anti-cancer drug-loaded nanocarriers for specific delivery to cancer cells and spare normal cells. Significant amounts of the drug loaded nanocarriers (92 ± 6 %) were found to distribute to the cancer cells at the tumour site and more interestingly, normal cells were unaffected in vitro and in vivo. In this review, the benefits of using nanoparticle-coated drugs in various cancer treatments are discussed. Various nanoparticles that have been tried in improving the target specificity and potency of chemotherapeutic compounds are also described.

scholarly journals Differential oxidative and pro-apoptotic response of cancer and normal cells to an anti-inflammatory agent CLEFMA

2021 ◽  
Author(s):  
Vibhudutta Awasthi ◽  
Kaustuv Sahoo
Keyword(s):  
Cancer Cells ◽  
Survival Data ◽  
Maximum Tolerated Dose ◽  
Binding Activity ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Normal Cells ◽  
Dna Binding Activity ◽  
Anti Inflammatory

Selective killing of cancer cells by chemotherapy has been an age old challenge, but certain unique features of cancer cells allow discriminatory response between cancer and normal cells. The objectives of this study was to investigate pro-oxidant and apoptotic effects of CLEFMA, an anti-inflammatory compound with anticancer activity, in lung cancer cells versus normal lung fibroblasts and to establish its maximum tolerated dose (MTD) in mice. We found that CLEFMA preferentially induced reactive oxygen species (ROS)-mediated apoptosis in H441, H1650 and H226 cancer cells, but spared normal CCL151 and MRC9 fibroblasts. Immunoblotting studies revealed that CLEFMA-induced apoptosis is associated with p53 phosphorylation in cancer cells which was not observed in CLEFMA treated normal fibroblasts. CLEFMA showed no effect on NF-κB p-65 expression in the normal lung fibroblasts, whereas its translocation to nucleus was inhibited in cancer cells. Furthermore, CLEFMA treatment also inhibited the DNA-binding activity of NF-κB p65 in H441cancer cells, but not in normal CCL151 cells. Preclinical toxicology studies in CD31 mice showed that CLEFMA was not toxic when injected daily for 7 days or injected weekly for 4 weeks. Based on survival data, MTD of CLEFMA was estimated as 30 mg/kg bodyweight. We conclude that CLEFMA exploits the biochemical differences in cancer and normal cells and selectively induces ROS in cancer cells. Secondly, CLEFMA can be safely administered in vivo because its known dose necessary for in vivo efficacy as anti-inflammatory and anti-tumor agent (0.4 mg/kg) is 75 times lower than its MTD.

scholarly journals Different Inhibitory Effect and Mechanism of Hydroxyapatite Nanoparticles on Normal Cells and Cancer Cells In Vitro and In Vivo

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Yingchao Han ◽  
Shipu Li ◽  
Xianying Cao ◽  
Lin Yuan ◽  
Youfa Wang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Inhibitory Effect ◽  
Hydroxyapatite Nanoparticles ◽  
Normal Cells

scholarly journals Erratum: CORRIGENDUM: Different Inhibitory Effect and Mechanism of Hydroxyapatite Nanoparticles on Normal Cells and Cancer Cells In Vitro and In Vivo

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Yingchao Han ◽  
Shipu Li ◽  
Xianying Cao ◽  
Lin Yuan ◽  
Youfa Wang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Inhibitory Effect ◽  
Hydroxyapatite Nanoparticles ◽  
Normal Cells

scholarly journals Methyl Jasmonate: Putative Mechanisms of Action on Cancer Cells Cycle, Metabolism, and Apoptosis

2014 ◽  
Vol 2014 ◽  
pp. 1-25 ◽  
Author(s):  
Italo Mario Cesari ◽  
Erika Carvalho ◽  
Mariana Figueiredo Rodrigues ◽  
Bruna dos Santos Mendonça ◽  
Nivea Dias Amôedo ◽  
...  
Keyword(s):  
Methyl Jasmonate ◽  
Cancer Cells ◽  
Anion Channel ◽  
Atp Depletion ◽  
Voltage Dependent Anion Channel ◽  
Normal Cells ◽  
Antiapoptotic Proteins ◽  
Mitochondrial Functions

Methyl jasmonate (MJ), an oxylipid that induces defense-related mechanisms in plants, has been shown to be active against cancer cells bothin vitroandin vivo, without affecting normal cells. Here we review most of the described MJ activities in an attempt to get an integrated view and better understanding of its multifaceted modes of action. MJ (1) arrests cell cycle, inhibiting cell growth and proliferation, (2) causes cell death through the intrinsic/extrinsic proapoptotic, p53-independent apoptotic, and nonapoptotic (necrosis) pathways, (3) detaches hexokinase from the voltage-dependent anion channel, dissociating glycolytic and mitochondrial functions, decreasing the mitochondrial membrane potential, favoring cytochromecrelease and ATP depletion, activating pro-apoptotic, and inactivating antiapoptotic proteins, (4) induces reactive oxygen species mediated responses, (5) stimulates MAPK-stress signaling and redifferentiation in leukemia cells, (6) inhibits overexpressed proinflammatory enzymes in cancer cells such as aldo-keto reductase 1 and 5-lipoxygenase, and (7) inhibits cell migration and shows antiangiogenic and antimetastatic activities. Finally, MJ may act as a chemosensitizer to some chemotherapics helping to overcome drug resistant. The complete lack of toxicity to normal cells and the rapidity by which MJ causes damage to cancer cells turn MJ into a promising anticancer agent that can be used alone or in combination with other agents.

scholarly journals Cancer-specific overmethylation of histone H3 lysines is necessary for methionine addiction and malignancy

2020 ◽  
Author(s):  
Jun Yamamoto ◽  
Sachiko Inubushi ◽  
Qinghong Han ◽  
Yoshihiko Tashiro ◽  
Yu Sun ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Therapeutic Target ◽  
Methylation Status ◽  
Histone H3 ◽  
Cell Types ◽  
Lysine Methylation ◽  
Normal Cells ◽  
Molecular Changes

AbstractMethionine addiction is a fundamental and general hallmark of cancer. Methionine addiction results from the overuse of methionine by cancer cells for excess transmethylation reactions. In order to identify excess transmethylation reactions in cancer, we compared the histone H3 lysine methylation status between methionine-addicted cancer cells, normal cells and revertants of methionine-addicted cancer cells which regained methionine independence and lost malignancy. The levels of H3K4me3, H3K9me3 and pan-methyl lysine of histone H3 were elevated in methionine-addicted cancer cells in vitro compared to methionine-independent revertants isolated from the cancer cells and to normal cells. Tumorigenicity in nude mice was highly reduced in the methionine-independent revertants compared to the parental cells. The methionine-independent revertants no longer overmethylated pan-methyl lysine of H3, H3K4me3 and H3K9me3. Our previous studies showed that methionine restriction (MR) selectively arrests methionine-addicted cancer cells due to loss of histone H3 lysine methylation, which was stable in normal cells under MR. Our previous and present results suggest that overmethylation of histone H3 lysine is necessary for methionine addiction of cancer, required for the growth of cancer cells in vitro and in vivo, and necessary for malignancy. Methionine addiction has revealed fundamental molecular changes necessary for malignancy and presents great potential as a pan-cancer therapeutic target.Signiificance StatementAll cancer cell types are methionine-addicted. Methionine addiction is due to the overuse of methionine by cancer cells for excess transmethylation reactions. In the present study, we showed that the level of histone H3 lysine methylation was elevated in methionine-addicted cancer cells compared to normal fibroblasts and methionine-independent revertants with reduced malignancy that were derived from the methionine-addicted cancer cells. These results suggest that overmethylation of histone H3 lysine is necessary for methionine addiction of cancer and malignancy itself. Methionine addiction has revealed fundamental molecular changes necessary for malignancy and has been shown to be a universal therapeutic target in numerous pre-clinical studies of all major cancer types and has great clinical potential.

scholarly journals Palladium nanoparticles encapsulated with resveratrol-derived phenols and polyphenols for targeted prostate cancer therapy

2019 ◽  
Author(s):  
◽  
Velaphi Clement Thipe
Keyword(s):  
Prostate Cancer ◽  
Cancer Cells ◽  
Palladium Nanoparticles ◽  
Gum Arabic ◽  
Prostate Tumor ◽  
Laminin Receptor ◽  
Prostate Cancer Cells ◽  
Normal Cells

The main goal of this dissertation was to explore the development of a new generation of green nanoformulations through the production of biocompatible palladium nanoparticles using resveratrol to treat, image and evaluate the efficacy of the formulations in prostate cancer cells with minimal toxicity to surrounding normal tissues. This dissertation is classified into three parts with three main objectives of the producing and characterizing resveratrol-derived phenols and polyphenols encapsulated palladium nanoparticles (Res-PdNPs) for the imaging and treatment of prostate cancer. Rigorous studies were performed for the optimization of the synthesis to achieve increased resveratrol-derived phenols and polyphenols corona loading on the palladium nanoparticle surface capable of providing adjuvant therapeutic benefits through delivering potent doses of both resveratrol phenols and nanoparticles directly to prostate cancer cells. A total of four formulations were produced Res-PdNP-1 (resveratrol-palladium nanoparticles), Res-PdNP-2 (increased resveratrol corona loaded palladium nanoparticles), Res-PdNP-3 (resveratrol-gum arabic stabilized palladium nanoparticles) and Res-PdNP-4 (increased resveratrol corona loaded and compacted with gum arabic stabilized palladium nanoparticles), respectively. Electron microscopic (TEM) results revealed that role of gum arabic was not limited to the stability of the nanoparticles but also facilitated the crystallization of the produced palladium nanoparticles (Res-PdNP-3 and Res-PdNP-4) and subsequently provided a supportive matrix for increased resveratrol phenols loading capacity. In vitro evaluation of the Res-PdNPs showed that Res-PdNP-1 and Res-PdNP-2, were not stable in serum while Res-PdNP-3 and Res-PdNP-4 maintained superior stability, thus ruling out further analysis using Res-PdNP-1 and Res-PdNP-2. The LC-MS/MRM results confirmed increased resveratrol phenols loading in Res-PdNP-4 when compared to Res-PdNP-3; consequently Res-PdNP-4 nanoparticles were confirmed as the ideal nanoformulation to improve the bioavailability, biodistribution and emblematize as an adjuvant therapy to induce selective and specific tumor-cell-death. The prostate tumor selective and specific affinity of Res-PdNP-4 nanoparticles through numerous cellular internalization studies undoubtedly revealed that Res-PdNP-4 nanoparticles can be internalized into prostate cancer cells via laminin receptor-mediated endocytosis which are receptors overexpressed on prostate cancer cells compared to normal cells. The Res-PdNP-4 nanoparticles were evaluated to investigate in vitro cellular toxicity against both prostate cancer (PC-3) cells and normal human aortic endothelial cells (HAEC). Results indicated that Res-PdNP-4 exhibited comparable anticancer efficacy against prostate cancer cells as chemotherapeutic drugs (cisplatin and etoposide). However, the results showed that cisplatin and etoposide treatments were highly toxic to normal cells while Res-PdNP-4 nanoparticles presented no toxicity further corroborating laminin receptor-mediated delivery, making Res-PdNP-4 nanoparticles selective and specific to prostate cancer cells. Res-PdNP-4 nanoparticles were investigated in vivo using a human prostate tumor-bearing severely combined immunodeficient (SCID) male mice as the animal model to evaluate Res-PdNP-4 nanoparticles ability to control or reduce prostate tumor size. The in vivo results of Res-PdNP-4 showed a good dose response which was well tolerated by the animals, as no animal health problems and discomfort was observed as evidenced by body weight/eating habits of animals. Although further studies are required to determine a better dose to see increased efficacy. This study was performed through intravenous (IV) administration of the Res-PdNP-4, intraperitoneal (IP) delivery and direct injection into the tumor may show a better response as has been the case with many different types of nanoparticles. In conclusion, the therapeutic efficacy results showed that Res-PdNP-4 have significant therapeutic effect and are able to control the tumor size in comparison to the saline control and free resveratrol treated groups. This was due to the high corona of resveratrol-derived phenols and polyphenols on the PdNPs facilitating effectively enhanced delivery of resveratrol with high bioavailability, giving an advantage in tumor therapy.

scholarly journals E-cadherin promotes cell hyper-proliferation in breast cancer

2020 ◽  
Author(s):  
Gabriella C. Russo ◽  
Michelle N. Karl ◽  
David Clark ◽  
Julie Cui ◽  
Ryan Carney ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Adhesion Molecule ◽  
Intercellular Adhesion ◽  
Normal Cells ◽  
Mesenchymal Transition ◽  
E Cadherin

ABSTRACTThe loss of the intercellular adhesion molecule E-cadherin is a hallmark of the epithelial-mesenchymal transition (EMT), which promotes a transition of cancer cells to a migratory and invasive phenotype. E-cadherin is associated with a decrease in cell proliferation in normal cells. Here, using physiologically relevant 3D in vitro models, we find that E-cadherin induces hyper-proliferation in breast cancer cells through activation of the Raf/MEK/ERK signaling pathway. These results were validated and consistent across multiple in vivo models of primary tumor growth and metastatic outgrowth. E-cadherin expression dramatically increases tumor growth and, without affecting the ability of cells to extravasate and colonize the lung, significantly increases macrometastasis formation via cell proliferation at the distant site. Pharmacological inhibition of MEK1/2, blocking phosphorylation of ERK in E-cadherin-expressing cells, significantly depresses both tumor growth and macrometastasis. This work suggests a novel role of E-cadherin in tumor progression and identifies a potential new target to treat hyper-proliferative breast tumors.SUMMARYE-cadherin, an extensively studied transmembrane molecule ubiquitously expressed in normal epithelial tissues, promotes and maintains intercellular adhesion. In cancer, the loss of adhesion molecule E-cadherin is associated with onset of invasion via epithelial-to-mesenchymal transition (EMT) process.1 EMT consists of a highly orchestrated cascade of molecular events where epithelial cells switch from a non-motile phenotype to an invasive, migratory phenotype accompanied by a change in cell morphology.1,2 These processes are believed to then trigger metastasis in carcinomas (cancers of epithelial origin). Moreover, the expression of intercellular adhesion molecule E-cadherin (E-cad) is associated with a decrease in cell proliferation in normal cells. Classical experiments in fibroblasts and epithelial cells show that the expression of E-cad not only promotes cell-cell adhesion, but also reduces cell proliferation and onset of apoptosis.3,4 Altogether these results have long supported that E-cad acts as a tumor suppressor gene.1,2However, despite its role in cell-adhesion the requirement for loss of E-cad in metastasis has recently been re-assessed.5,6,7,8These investigations focus on E-cad’s role in EMT, even though the relationship between E-cad and proliferation is just as intriguing. While E-cad has been shown to have anit-proliferative effects in normal cells, E-cad also helps maintain a pluripotent and proliferative phenotype in stem cells, and notably is lost during differentiation, a non-proliferative step of stem cell progression.9,10 Yet, despite potentially important implications in our understanding of tumor progression, whether E-cad expression affects growth in cancer cells remains mostly unexplored.Here, utilizing a physiologically relevant 3D in vitro model and multiple in vivo models, we studied the impact of E-cad on cell proliferation at the primary tumor site and proliferation at a secondary site. Remarkably, E-cad upregulates multiple proliferation pathways, including hyper-activation of the ERK cascade within the greater MAPKinase pathway, resulting in a dramatic increase in cell proliferation in vitro and tumor growth in vivo. When the phosphorylation of ERK is blocked utilizing a MEK1/2 inhibitor, PD032590111, this effect is reversed in vitro and in vivo. Thus, E-cad plays an oncogenic role in tumorigenesis and merits evaluation as a potential new drug target.

A near-infrared fluorescent probe for accurately diagnosing cancer by sequential detection of cysteine and H+

2021 ◽  
Author(s):  
Zun-Pan She ◽  
Wen-Xin Wang ◽  
Guo-Jiang Mao ◽  
Wen-Li Jiang ◽  
Zhi-Qing Wang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Fluorescent Probe ◽  
Near Infrared ◽  
Sequential Detection ◽  
Normal Cells

A near-infrared fluorescent probe, CyAc, is synthesized for accurately diagnosing cancer in vivo by sequential detection of Cys and H+. CyAc can not only discriminate normal cells and cancer cells, but also distinguish normal mice from tumor mice.

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