Evaluation of Anti-Tumorigenic Effects of Diosmetin against Human Colon Cancer Xenografts in Athymic Nude Mice

Colon cancer is the third most common type of cancer in the world. Diosmetin (Dis), a natural O-methylated flavone, has been reported to have anti-cancer effects against different types of cancer. Although the mechanisms of action of Dis against several cancer cell lines are well reported, in vivo anti-tumorigenesis properties of this compound are still obscure. Therefore, this study aimed to investigate the anti-tumorigenesis properties of Dis against HCT-116 colon cancer xenografts in nude mice. HCT-116 colon cancer cells were injected in NCr nu/nu nude mice and treatment with Dis was initiated after the tumor volumes reached 100 mm3 and continued for four weeks. On the sacrificing date nude mice treated with 100 mg/kg of Dis showed significant lower tumor volume (264 ± 238.3 mm3) as compared to the untreated group (1428.8 ± 459.6 mm3). Anti-apoptotic Bcl-2 protein was significantly downregulated, while apoptotic protein (Bax) was significantly overexpressed in nude mice treated with 100 mg/kg Dis as compared to untreated mice. In conclusion, our in vivo results indicate that Dis significantly reduces tumor growth rate of HCT-116 colon cancer cells in nude mice at a dose of 100 mg/kg, and has no toxic effects in ICR mice up to 2000 mg/kg.

Download Full-text

Leptin stimulates the proliferation of human colon cancer cells in vitro but does not promote the growth of colon cancer xenografts in nude mice or intestinal tumorigenesis in ApcMin/+ mice

Gut ◽

10.1136/gut.2004.060533 ◽

2005 ◽

Vol 54 (8) ◽

pp. 1136-1145 ◽

Cited By ~ 68

Author(s):

T Aparicio

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Nude Mice ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Intestinal Tumorigenesis ◽

Human Colon Cancer Cells

Download Full-text

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

Cancer Medicine ◽

10.1002/cam4.2409 ◽

2019 ◽

Vol 8 (12) ◽

pp. 5662-5672 ◽

Cited By ~ 3

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

Download Full-text

NF-κB maintains the stemness of colon cancer cells by downregulating miR-195-5p/497–5p and upregulating MCM2

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-020-01704-w ◽

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.

Download Full-text

Effect on in vivo tumorigenicity of lengthy exposure of human colon cancer cells to the differentiation agent hexamethylene bisacetamide

Cancer Letters ◽

10.1016/0304-3835(89)90202-4 ◽

1989 ◽

Vol 48 (1) ◽

pp. 53-58 ◽

Cited By ~ 4

Author(s):

P. Schroy ◽

S. Winawer ◽

E. Friedman

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Hexamethylene Bisacetamide ◽

Human Colon Cancer Cells

Download Full-text

Identification of a thymidylate synthase ribonucleoprotein complex in human colon cancer cells.

Molecular and Cellular Biology ◽

10.1128/mcb.14.1.207 ◽

1994 ◽

Vol 14 (1) ◽

pp. 207-213 ◽

Cited By ~ 53

Author(s):

E Chu ◽

D M Voeller ◽

K L Jones ◽

T Takechi ◽

G F Maley ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Thymidylate Synthase ◽

Translational Regulation ◽

Direct Interaction ◽

Human Colon ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Human Colon Cancer Cells

Translation of thymidylate synthase (TS) mRNA is controlled by its own protein product, TS, in an autoregulatory manner. Direct binding of TS protein to two different cis-acting elements on the TS mRNA is associated with this translational regulation. In this study, an immunoprecipitation-reverse transcription-PCR technique was used to identify a TS ribonucleoprotein (RNP) complex in cultured human colon cancer cells. Using antibodies specific for TS protein, we show that TS is complexed in vivo with its own TS RNA. Furthermore, evidence demonstrating a direct interaction between the mRNA of the nuclear oncogene c-myc and TS protein is presented.

Download Full-text