Rotundic Acid Regulates the Effects of Let-7f-5p on Caco2 Cell Proliferation

Author(s):  
Yuan Feng ◽  
Xinran Liu ◽  
Yueqing Han ◽  
Mantian Chen ◽  
Lin Zhang ◽  
...  

Background & Objective: Nowadays, the interaction between natural products and microRNAs provides a promising field for exploring the chemo preventive agents for various cancers.As a member of microRNAs, the expression of let-7f-5p is universally down regulated in colorectal cancer (CRC). The present study aimed to uncover the function of let-7f-5p in the proliferation of human colon cancer cell line Caco2 and explored chemo preventive agents from natural resources that can prevent the development of CRC. Methods: Herein, Caco2 cells were transfected with let-7f-5p mimic and inhibitor to manipulate let-7f-5p levels, and the expression of let-7f-5p wasper formed by RT‑qPCR. Next, we determined how let-7f-5p regulates Caco2 cell proliferation by using MTT, wound-healing, cell cycle,and colony formation assays.Besides, to further understand the effect of let-7f-5p, we evaluated the protein level of AMER3 and SLC9A9 by using western blotting assays. Results: The results showed a suppressive function of let-7f-5p on Caco2 cell proliferation and then put forward a triterpenoid (rotundic acid, RA) which significant antagonized the effect of cell proliferation, restitution after wounding,and colony formation caused by let-7f-5p. Moreover, the western blot results further indicated that the inhibitory effect of RA might be due to its suppressive role in let-7f-5p-targeted AMER3 and SLC9A9 regulation. Conclusion: Our validation study results confirmed that let-7f-5p was a potent tumor suppressor gene of Caco2 cell proliferation,and RA showed as a regulator of the effect oflet-7f-5p on cell proliferation and then could be a potential chemo preventive agent for CRC treatment.

2005 ◽  
Vol 12 (2) ◽  
pp. 455-469 ◽  
Author(s):  
Valentina Martineti ◽  
Lucia Picariello ◽  
Isabella Tognarini ◽  
Silvia Carbonell Sala ◽  
Alessia Gozzini ◽  
...  

Several strands of evidence indicate that oestrogens exert a protective role against the development of colon cancer through indirect and direct effects on colonic epithelium. Oestrogen receptor β (ERβ), the predominant ER subtype in human colon, is significantly decreased in colonic tumours compared with normal mucosa suggesting a potential role in the regulation of colon tumour growth. To investigate this hypothesis we engineered human colon cancer ERα-negative HCT8 cells in order to obtain ERβ protein over-expression. Stably transfected cells were cloned and ERβ expression and functionality were monitored by RT-PCR, Western blotting and transactivation in an assay using oestrogen-responsive reporter constructs. Over-expression of ERβ inhibited cell proliferation and increased cell adhesion in a ligand-independent manner. Its constitutive activation is possibly due to cross-talk with intracellular signalling pathways, as epidermal growth factor and IGF-I were able to induce ERβ transactivation. A possible mechanism by which ERβ over-expression inhibits proliferation in HCT8 cells is by modulation of some key regulators of the cell cycle; there is a decrease in cyclin E and an increase in the cdk inhibitor p21CIP1. In fact, flow cytometry analysis provided evidence for blocking of the G1-S phase progression induced by ERβ over-expression. The magnitude of this effect was affected by the level of ERβ expression. These results provide the first direct evidence that ERβ plays an important role in colon cancer as a regulator of cell proliferation through the control of key cell cycle modulators and arrest in G1-S phase transition. These findings are compatible with the hypothesis that the loss of ERβ expression could be one of the events involved in the development or progression of colon cancer.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chen-Chen Huang ◽  
Fang-Rui Liu ◽  
Qiang Feng ◽  
Xin-Yan Pan ◽  
Shu-Ling Song ◽  
...  

An amendment to this paper has been published and can be accessed via the original article.


2009 ◽  
Vol 124 (6) ◽  
pp. 1322-1329 ◽  
Author(s):  
Chiara Laezza ◽  
Maria Gabriella Caruso ◽  
Teresa Gentile ◽  
Maria Notarnicola ◽  
Anna Maria Malfitano ◽  
...  

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