ALA-mediated photodynamic effect on apoptosis induction and secretion of macrophage migration inhibitory factor (MIF) and of monocyte chemotactic protein (MCP-1) by colon cancer cells in normoxia and in hypoxia-like conditions in vitro

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.

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In Vitro Collapsing Colon Cancer Cells by Selectivity of Disulfiram-Loaded Charge Switchable Nanoparticles Against Cancer Stem Cells

Recent Patents on Anti-Cancer Drug Discovery ◽

10.2174/1574892812666170424144925 ◽

2017 ◽

Vol 12 (3) ◽

Cited By ~ 7

Author(s):

Marwa M. Abu-Serie ◽

Fatma H. El-Rashidy

Keyword(s):

Stem Cells ◽

Colon Cancer ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Colon Cancer Cells

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CXCL2-CXCR2 axis mediates αV integrin-dependent peritoneal metastasis of colon cancer cells

Clinical & Experimental Metastasis ◽

10.1007/s10585-021-10103-0 ◽

2021 ◽

Author(s):

Mattias Lepsenyi ◽

Nader Algethami ◽

Amr A. Al-Haidari ◽

Anwar Algaber ◽

Ingvar Syk ◽

...

Keyword(s):

Colon Cancer ◽

Cell Adhesion ◽

Cancer Cells ◽

Cancer Cell ◽

Colon Cancer Cell ◽

Colon Cancer Cells ◽

Cancer Cell Adhesion ◽

And Migration ◽

Cxcr2 Antagonist

AbstractPeritoneal metastasis is an insidious aspect of colorectal cancer. The aim of the present study was to define mechanisms regulating colon cancer cell adhesion and spread to peritoneal wounds after abdominal surgery. Mice was laparotomized and injected intraperitoneally with CT-26 colon carcinoma cells and metastatic noduli in the peritoneal cavity was quantified after treatment with a CXCR2 antagonist or integrin-αV-antibody. CT-26 cells expressed cell surface chemokine receptors CXCR2, CXCR3, CXCR4 and CXCR5. Stimulation with the CXCR2 ligand, CXCL2, dose-dependently increased proliferation and migration of CT-26 cells in vitro. The CXCR2 antagonist, SB225002, dose-dependently decreased CXCL2-induced proliferation and migration of colon cancer cells in vitro. Intraperitoneal administration of CT-26 colon cancer cells resulted in wide-spread growth of metastatic nodules at the peritoneal surface of laparotomized animals. Laparotomy increased gene expression of CXCL2 at the incisional line. Pretreatment with CXCR2 antagonist reduced metastatic nodules by 70%. Moreover, stimulation with CXCL2 increased CT-26 cell adhesion to extracellular matrix (ECM) proteins in a CXCR2-dependent manner. CT-26 cells expressed the αV, β1 and β3 integrin subunits and immunoneutralization of αV abolished CXCL2-triggered adhesion of CT-26 to vitronectin, fibronectin and fibrinogen. Finally, inhibition of the αV integrin significantly attenuated the number of carcinomatosis nodules by 69% in laparotomized mice. These results were validated by use of the human colon cancer cell line HT-29 in vitro. Our data show that colon cancer cell adhesion and growth on peritoneal wound sites is mediated by a CXCL2-CXCR2 signaling axis and αV integrin-dependent adhesion to ECM proteins.

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