scholarly journals Folic Acid Conjugated PEG-PCL-PEG Triblock Copolymer Nanoparticles for Enhanced Delivery of 5-Fluorouracil to HT29 Colon Cancer Cells

2020 ◽  
Author(s):  
Parvin Sadat Mirzaghavami ◽  
Samideh Khoei ◽  
Sepideh Khoee ◽  
Sakine Shirvalilou
Keyword(s):  
Colon Cancer ◽  
Folic Acid ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Colony Formation ◽  
Triblock Copolymer ◽  
Therapeutic Index ◽  
Ros Production ◽  
Colon Cancer Cells ◽  
Antitumor Effects

Abstract Background: In the current study, folic acid conjugated magnetite PEG-PCL-PEG triblock copolymer were synthesized and loaded with 5-Fluorouracil (5-FU-SPION-PEG-PCL-PEG-FA) for targeted delivery of drug to HT29 colon cancer cells.Methods: The cytotoxic effect and cellular uptake of synthesized nanoparticles was assessed on HUVEC and HT29 cell lines. In addition, antitumor effects of nanoparticles were investigated based on gene expression of Bax and Bcl2, Annexin V/PI staining, ROS production and colony formation.Results: As compared to 5-FU, an improvement in therapeutic index was demonstrated for 5-FU-SPION-PEG-PCL-PEG-FA according to cytotoxicity induced in HUVEC and HT29 cells. In addition, 5-FU-SPION-PEG-PCL-PEG-FA was found to be more antitumor efficient in comparison to 5-FU based on Bax/Bcl2 ratio, percentage of cell death, ROS production and colony formation ability (P<0.05).Conclusion: The obtained results suggested that 5-FU-SPION-PEG-PCL-PEG-FA could be considered as promising targeted drug delivery system.

scholarly journals Effective Targeting of Colon Cancer Cells with Piperine Natural Anticancer Prodrug Using Functionalized Clusters of Hydroxyapatite Nanoparticles

Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 70 ◽  
Author(s):  
Khaled AbouAitah ◽  
Agata Stefanek ◽  
Iman M. Higazy ◽  
Magdalena Janczewska ◽  
Anna Swiderska-Sroda ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Folic Acid ◽  
Cancer Cells ◽  
Delivery System ◽  
Targeted Delivery ◽  
Gum Arabic ◽  
Colon Cancer Cells ◽  
Hydroxyapatite Nanoparticles ◽  
Anticancer Effects ◽  
Targeted Delivery System

Targeted drug delivery offers great opportunities for treating cancer. Here, we developed a novel anticancer targeted delivery system for piperine (Pip), an alkaloid prodrug derived from black pepper that exhibits anticancer effects. The tailored delivery system comprises aggregated hydroxyapatite nanoparticles (HAPs) functionalized with phosphonate groups (HAP-Ps). Pip was loaded into HAPs and HAP-Ps at pH 7.2 and 9.3 to obtain nanoformulations. The nanoformulations were characterized using several techniques and the release kinetics and anticancer effects investigated in vitro. The Pip loading capacity was >20%. Prolonged release was observed with kinetics dependent on pH, surface modification, and coating. The nanoformulations fully inhibited monolayer HCT116 colon cancer cells compared to Caco2 colon cancer and MCF7 breast cancer cells after 72 h, whereas free Pip had a weaker effect. The nanoformulations inhibited ~60% in HCT116 spheroids compared to free Pip. The Pip-loaded nanoparticles were also coated with gum Arabic and functionalized with folic acid as a targeting ligand. These functionalized nanoformulations had the lowest cytotoxicity towards normal WI-38 fibroblast cells. These preliminary findings suggest that the targeted delivery system comprising HAP aggregates loaded with Pip, coated with gum Arabic, and functionalized with folic acid are a potentially efficient agent against colon cancer.

scholarly journals ADCK1 activates the β-catenin/TCF signaling pathway to promote the growth and migration of colon cancer cells

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yong Ji ◽  
Yiqian Liu ◽  
Changchun Sun ◽  
Lijiang Yu ◽  
Zhao Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Colony Formation ◽  
Activation Mechanism ◽  
Colon Cancer Cells ◽  
Mechanistic Studies ◽  
T Cell Factor ◽  
And Migration

AbstractAs a result of mutations in the upstream components of the Wnt/β-catenin signaling pathway, this cascade is abnormally activated in colon cancer. Hence, identifying the activation mechanism of this pathway is an urgent need for the treatment of colon cancer. Here, we found an increase in ADCK1 (AarF domain-containing kinase 1) expression in clinical specimens of colon cancer and animal models. Upregulation of ADCK1 expression promoted the colony formation and infiltration of cancer cells. Downregulation of ADCK1 expression inhibited the colony formation and infiltration of cancer cells, in vivo tumorigenesis, migration, and organoid formation. Molecular mechanistic studies demonstrated that ADCK1 interacted with TCF4 (T-cell factor 4) to activate the β-catenin/TCF signaling pathway. In conclusion, our research revealed the functions of ADCK1 in the development of colon cancer and provided potential therapeutic targets.

Effects of LPA1 and LPA6 on the regulation of colony formation activity in colon cancer cells treated with anticancer drugs

2018 ◽  
Vol 38 (1) ◽  
pp. 71-75 ◽  
Author(s):  
Kaede Takahashi ◽  
Kaori Fukushima ◽  
Shiho Otagaki ◽  
Kaichi Ishimoto ◽  
Kanako Minami ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Colony Formation ◽  
Colon Cancer Cells

scholarly journals Synergistic tumor inhibition of colon cancer cells by nitazoxanide and obeticholic acid, a farnesoid X receptor ligand

2020 ◽  
Author(s):  
Junhui Yu ◽  
Kui Yang ◽  
Jianbao Zheng ◽  
Wei Zhao ◽  
Xuejun Sun
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Farnesoid X Receptor ◽  
Colon Cancer Cells ◽  
Antitumor Effects ◽  
Colorectal Tumorigenesis ◽  
Tumor Inhibition ◽  
Combination Study

Abstract The tumor-suppressive role of Farnesoid X receptor (FXR) in colorectal tumorigenesis supports restoring FXR expression as a novel therapeutic strategy. However, the complicated signaling network and tumor heterogeneity hinder the effectiveness of FXR agonists in the clinical setting. These difficulties highlight the importance of identifying drug combinations with potency and specificity to enhance the antitumor effects of FXR agonists. In this study, we found that the β-catenin level affected the antitumor effects of the FXR agonist OCA on colon cancer cells. Mechanistic studies identified a novel FXR/β-catenin complex in colon cancer cells. Furthermore, the depletion of β-catenin expedited FXR nuclear localization and enhanced its occupancy of the SHP promoter and thereby sensitized colon cancer cells to OCA. Furthermore, we utilized a drug combination study and identified that the antiparasitic drug nitazoxanide (NTZ) abrogated β-catenin expression and acted synergistically with OCA in colon cancer cells. The combination of OCA plus NTZ exerts synergistic tumor inhibition in CRC both in vitro and in vivo by cooperatively upregulating SHP expression. In conclusion, our study offers useful evidence for the clinical use of FXR agonists combined with β-catenin inhibitors in combating CRC.

scholarly journals PADI3 plays an antitumor role via the Hsp90/CKS1 pathway in colon cancer

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhengbin Chai ◽  
Li Wang ◽  
Yabing Zheng ◽  
Na Liang ◽  
Xiwei Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Molecular Mechanism ◽  
Expression Pattern ◽  
Colony Formation ◽  
Regulatory Mechanism ◽  
Cancer Cell Proliferation ◽  
Colon Cancer Cells ◽  
Cancer Tissues

Abstract Background CKS1 is highly expressed in colon cancer tissues, and is essential for cancer cell proliferation. The downstream molecular mechanism of CKS1 has been fully studied, but the upstream regulatory mechanism of it is still unclear. Earlier research found that PADI3 plays its anti-tumor roles via suppress cell proliferation, in this study, we found that the expression pattern of PADI3 and CKS1 are negatively correlated in colon cancer tissues, and overexpression of PADI3 can partly reverse CKS1 induced cancer cell proliferation. However, the regulatory mechanism of PADI3 and CKS1 in the tumorigenesis of colon cancer is still unclear and need to do further research. Methods Western blot and real-time PCR were used to detect the expression levels of genes. CCK-8 and colony formation assays were used to examine cell proliferation and colony formation ability. Overexpression and rescue experiments were used to study the molecular mechanism of CKS1 in colon cancer cells, BALB/c nude mice were used to study the function of CKS1 in vivo. Results CKS1 is highly expressed in colon cancer tissues, and the overexpression of CKS1 promotes cell proliferation and colony formation in both HCT116 (originating from primary colon cancer) and SW620 (originating from metastatic tumor nodules of colon cancer) cells. CKS1-expressing HCT116 cells produced larger tumors than the control cells. The expression pattern of PADI3 and CKS1 are negatively correlation in clinical samples of colon cancer, further study indicates that PADI3 can significantly decrease Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to downregulate CKS1expression in colon cancer cells. Conclusions PADI3 exerts its antitumor activity by inhibiting Hsp90 and CKS1 expression, and Hsp90 is essential for PADI3 to suppress CKS1 expression.

Targeted delivery of small interfering RNA to colon cancer cells using chitosan and PEGylated chitosan nanoparticles

2016 ◽  
Vol 147 ◽  
pp. 323-332 ◽  
Author(s):  
Walter E. Rudzinski ◽  
Adriana Palacios ◽  
Abuzar Ahmed ◽  
Michelle A. Lane ◽  
Tejraj M. Aminabhavi
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Small Interfering Rna ◽  
Chitosan Nanoparticles ◽  
Colon Cancer Cells ◽  
Interfering Rna
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