scholarly journals Redox-Responsive Nanophotosensitizer Composed of Chlorin e6-Conjugated Dextran for Photodynamic Treatment of Colon Cancer Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Chong Woo Chu ◽  
Je Ho Ryu ◽  
Young-IL Jeong ◽  
Tae Won Kwak ◽  
Hye Lim Lee ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Chlorin E6 ◽  
Colon Cancer Cells ◽  
Photodynamic Treatment ◽  
Disulfide Linkage ◽  
Tumor Tissues ◽  
Redox Responsive ◽  
End Group

We synthesized dextran-chlorin e6 conjugates having disulfide linkage for specific targeting of colonic region and cancer cells. Reductive end group of dextran was treated with sodium borocyanohydride and conjugated with cystamine. Cystamine end group was conjugated with carboxylic acid of chlorin e6 (DEX6ss). DEX6ss conjugates were formed as spherical nanoparticles with small sizes less than 100 nm. Chlorin e6 (Ce6) was specifically released from DEX6ss nanoparticles in the presence of dextranase or glutathione (GSH), indicating that DEX6ss nanoparticles have responsiveness against dextranase and redox-environment. In dark-toxicity test using normal cells and cancer cells, Ce6 and DEX6ss nanoparticles were practically nontoxic. Intracellular delivery of DEX6ss nanoparticles was significantly improved compared to Ce6 itself. DEX6ss nanoparticles achieved significantly higher ROS production and phototoxicity against HCT116 colon cancer cells than Ce6 itself. Furthermore, DEX6ss nanoparticles showed enhanced tumor targeting efficiency and longer retention in the tumor tissues atin vivoanimal study with HCT116 tumor-bearing mice. Furthermore, DEX6ss nanoparticles have responsiveness against colonic enzyme, dextranase, indicating that they have potential of colon-specific delivery and dextranase-specific drug delivery capacity. We fabricated colon-specific and tumor-targetable nanophotosensitizer using DEX6ss conjugates. They showed improved cellular uptake ratio, phototoxicity, and colon-specificity. We suggest that DEX6ss nanoparticles can be considered as a promising candidate for PDT of colon cancer.

scholarly journals The Anticancer Action of a Novel 1,2,4-Triazine Sulfonamide Derivative in Colon Cancer Cells

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2045
Author(s):  
Agnieszka Gornowicz ◽  
Anna Szymanowska ◽  
Mariusz Mojzych ◽  
Robert Czarnomysy ◽  
Krzysztof Bielawski ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cathepsin B ◽  
Beclin 1 ◽  
Special Role ◽  
The Novel ◽  
Colon Cancer Cells ◽  
Sulfonamide Derivative

Cancer therapy is one of the most important challenges of modern medical and chemical sciences. Among the many methods of combating cancer, chemotherapy plays a special role. Imperfect modern chemotherapy justifies continuing the search for new, more effective, and safe drugs. Sulfonamides are the classic group of chemotherapeutic drugs with a broad spectrum of pharmacological activity. Recent literature reports show that sulfonamide derivatives have anti-tumor activity in vitro and in vivo. The aim of the study was to synthesize a novel 1,2,4-triazine sulfonamide derivative and check its anticancer potential in DLD-1 and HT-29 colon cancer cells. The biological studies included MTT assay, DNA biosynthesis, cell cycle analysis, Annexin V binding assay, ethidium bromide/acridine orange staining, and caspase-8, -9, and -3/7 activity. The concentrations of important molecules (sICAM-1, mTOR, Beclin-1, cathepsin B) involved in the pathogenesis and poor prognosis of colorectal cancer were also evaluated by ELISA. We demonstrated that the novel compound was able to induce apoptosis through intrinsic and extrinsic pathways and was capable of decreasing sICAM-1, mTOR, cathepsin B concentrations, whereas increased Beclin-1 concentration was detected in both colon cancer cell lines. The novel compound represents promising multi-targeted potential in colorectal cancer, but further in vivo examinations are needed to confirm the claim.

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.

scholarly journals Destruxin B Suppresses Drug-Resistant Colon Tumorigenesis and Stemness Is Associated with the Upregulation of miR-214 and Downregulation of mTOR/β-Catenin Pathway

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 353 ◽  
Author(s):  
Szu-Yuan Wu ◽  
Yan-Jiun Huang ◽  
Yew-Min Tzeng ◽  
Chi-Ying Huang ◽  
Michael Hsiao ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Side Population ◽  
Colon Cancer Cells ◽  
Cancer Stemness ◽  
Colon Cells ◽  
Colon Tumorigenesis ◽  
Tumor Sphere ◽  
Sphere Formation

Background: Drug resistance represents a major challenge for treating patients with colon cancer. Accumulating evidence suggests that Insulin-like growth factor (IGF)-associated signaling promotes colon tumorigenesis and cancer stemness. Therefore, the identification of agents, which can disrupt cancer stemness signaling, may provide improved therapeutic efficacy. Methods: Mimicking the tumor microenvironment, we treated colon cancer cells with exogenous IGF1. The increased stemness of IGF1-cultured cells was determined by ALDH1 activity, side-population, tumor sphere formation assays. Destruxin B (DB) was evaluated for its anti-tumorigenic and stemness properties using cellular viability, colony-formation tests. The mimic and inhibitor of miR-214 were used to treat colon cancer cells to show its functional association to DB treatment. In vivo mouse models were used to evaluate DB’s ability to suppress colon tumor-initiating ability and growth inhibitory function. Results: IGF1-cultured colon cancer cells showed a significant increase in 5-FU resistance and enhanced stemness properties, including an increased percentage of ALDH1+, side-population cells, tumor sphere generation in vitro, and increased tumor initiation in vivo. In support, using public databases showed that increased IGF1 expression was significantly associated with a poorer prognosis in patients with colon cancer. DB, a hexadepsipeptide mycotoxin, was able to suppress colon tumorigenic phenotypes, including colony and sphere formation. The sequential treatment of DB, followed by 5-FU, synergistically inhibited the viability of colon cancer cells. In vivo studies showed that DB suppressed the tumorigenesis by 5-FU resistant colon cells, and in a greater degree when combined with 5-FU. Mechanistically, DB treatment was associated with decreased the mammalian target of rapamycin (mTOR) and β-catenin expression and an increased miR-214 level. Conclusion: We provided evidence of DB as a potential therapeutic agent for overcoming 5-FU resistance induced by IGF1, and suppressing cancer stem-like properties in association with miR-214 regulation. Further investigation is warranted for its translation to clinical application.

932 Targeting the 19S Proteasomal Subunit, Rpt4, in Colon Cancer Cells Induces Cell Death and Reduces Cellular Proliferation In Vitro and In Vivo

2013 ◽  
Vol 144 (5) ◽  
pp. S-166-S-167
Author(s):  
Karen Boland ◽  
Caoimhin Concannon ◽  
Niamh McCawley ◽  
Elaine W. Kay ◽  
Deborah McNamara ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cell Death ◽  
Cancer Cells ◽  
Cellular Proliferation ◽  
Colon Cancer Cells ◽  
Proliferation In Vitro

scholarly journals In Vitro and in Vivo antitumor activity and the mechanism of siphonodictyal B in human colon cancer cells

2019 ◽  
Vol 8 (12) ◽  
pp. 5662-5672 ◽  
Author(s):  
Sonoko Chikamatsu ◽  
Ken Saijo ◽  
Hiroo Imai ◽  
Koichi Narita ◽  
Yoshifumi Kawamura ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Antitumor Activity ◽  
Cancer Cells ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Human Colon Cancer ◽  
In Vivo Antitumor Activity ◽  
Human 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 NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Longgang Wang ◽  
Jinxiang Guo ◽  
Jin Zhou ◽  
Dongyang Wang ◽  
Xiuwen Kang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Human Colon ◽  
Colon Cancer Cells ◽  
Tumor Models ◽  
Human Colon Cancer ◽  
Subcutaneous Tumor

Abstract Background Colon cancer represents one of the leading causes of gastrointestinal tumors in industrialized countries, and its incidence appears to be increasing at an alarming rate. Accumulating evidence has unveiled the contributory roles of cancer stem cells (CSCs) in tumorigenicity, recurrence, and metastases. The functions of NF-kappa B (NF-κB) activation on cancer cell survival, including colon cancer cells have encouraged us to study the role of NF-κB in the maintenance of CSCs in colon cancer. Methods Tumor samples and matched normal samples were obtained from 35 colon cancer cases. CSCs were isolated from human colon cancer cell lines, where the stemness of the cells was evaluated by cell viability, colony-forming, spheroid-forming, invasion, migration, and apoptosis assays. NF-κB activation was then performed in subcutaneous tumor models of CSCs by injecting lipopolysaccharides (LPS) i.p. Results We found that NF-κB activation could reduce the expression of miR-195-5p and miR-497-5p, where these two miRNAs were determined to be downregulated in colon cancer tissues, cultured colon CSCs, and LPS-injected subcutaneous tumor models. Elevation of miR-195-5p and miR-497-5p levels by their specific mimic could ablate the effects of NF-κB on the stemness of colon cancer cells in vivo and in vitro, suggesting that NF-κB could maintain the stemness of colon cancer cells by downregulating miR-195-5p/497–5p. MCM2 was validated as the target gene of miR-195-5p and miR-497-5p in cultured colon CSCs. Overexpression of MCM2 was shown to restore the stemness of colon cancer cells in the presence of miR-195-5p and miR-497-5p, suggesting that miR-195-5p and miR-497-5p could impair the stemness of colon cancer cells by targeting MCM2 in vivo and in vitro. Conclusions Our work demonstrates that the restoration of miR-195-5p and miR-497-5p may be a therapeutic strategy for colon cancer treatment in relation to NF-κB activation.

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