Affiliation:
1. Department of Medical Imaging and Radiological Sciences Central Taiwan University of Science and Technology Taichung Taiwan
2. Department of Radiation Oncology Chang Bing Show Chwan Memorial Hospital Changhua Taiwan
3. Institute of Biotechnology National Tsing Hua University Hsinchu Taiwan
4. Department of Biological Science and Technology China Medical University Taichung Taiwan
5. Department of Radiation Oncology National Yang Ming Chiao Tung University Hospital Yilan Taiwan
Abstract
AbstractColorectal cancer (CRC) is recognized as the third most common malignancy and the second most deadly in highly developed countries. Although the treatment of CRC has improved in the past decade, the mortality rate of CRC is still increasing. Amentoflavone, one of the flavonoids detected in medical plants, is reported to possess potential anticancer properties in various cancers. However, its role in CRC has not been studied. This study aimed to investigate the role and underlying mechanism of amentoflavone on CRC in vitro and in vivo. We identified the cytotoxicity, apoptosis effect, cell cycle alteration, DNA damage induction and tumor progression inhibition of amentoflavone in HT‐29 model by using MTT assay, flow cytometry, immunofluorescence (IF) staining, Western blotting and animal experiments. Amentoflavone induced cytotoxicity is caused by triggering G1 arrest, DNA damage and apoptosis in HT‐29 cells. The expression of cyclin D1, CDK4 and CDK6 was decreased by amentoflavone; in contrast, the phosphorylation of ATM and CHK2 and the expression of p21 and p27 were increased. The apoptosis induction of amentoflavone in CRC is not only caspase‐dependent but also increases EndoG and AIF nuclear translocation in a caspase‐independent manner. Importantly, the apoptosis induction of amentoflavone is not affected by the activity of p53 in CRC. Amentoflavone suppressed the progression of CRC by initiating G1 arrest and ATM/CHK2‐mediated DNA damage‐responsive, caspase‐dependent/independent apoptotic effects. We uncovered a novel tumor‐inhibitory role of amentoflavone in CRC that is not associated with p53 activity, which may serve as a potential treatment for CRC.
Funder
Chang Bing Show Chwan Memorial Hospital
China Medical University, Taiwan
Subject
Health, Toxicology and Mutagenesis,Management, Monitoring, Policy and Law,Toxicology,General Medicine
Cited by
2 articles.
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