Retracted: Pancratistatin Inhibits the Growth of Colorectal Cancer Cells by Inducing Apoptosis, Autophagy, and G2/M Cell Cycle Arrest.

An editorial decision has been made to retract this manuscript due to breach of publishing guidelines, following the identification of non-original and manipulated figures.Reference:Yong Xiong, Yi-Jia Xiong, Dong-Yang Liu, Rong-Rong Shen: Pancratistatin Inhibits the Growth of Colorectal Cancer Cells by Inducing Apoptosis, Autophagy, and G2/M Cell Cycle Arrest.Med Sci Monit 2019; 25:6015-6022. 10.12659/MSM.916116.

Pancratistatin Inhibits the Growth of Colorectal Cancer Cells by Inducing Apoptosis, Autophagy, and G2/M Cell Cycle Arrest.

BACKGROUND Worldwide, colorectal cancer is ranked as the third most prevalent cancer. The natural compound, pancratistatin, extracted from the spider lily, has previously been shown to target apoptosis in cancer cells lines. This study aimed to investigate the effects of pancratistatin in human colorectal cancer cells in vitro. MATERIAL AND METHODS Human colorectal cancer cell lines, including HTC-15 cells, were compared with a normal human colonic fibroblast cell line, CDD-18Co. Cells were treated with increasing doses of pancratistatin. The MTT assay was used to assess cell viability. Fluorescence microscopy using DAPI and Annexin-V/propidium iodide (PI) was used to detect cell apoptosis. Cell autophagy was detected by electron microscopy. Cell migration was evaluated using a wound healing assay, and Western blot determined the expression levels of cell cycle proteins. RESULTS Pancratistatin inhibited the growth of the colorectal cancer cells with an IC50 ranging from 15-25 µM, but had a limited effect in normal CCD-18Co cells, with an IC50 of >100 µM. Pancratistatin reduced HCT-15 cell migration. Growth inhibition due to pancratistatin was associated with morphological changes of HCT-15 cells and included autophagy and apoptosis, and increased expression the autophagic proteins, LC3II, beclin-1, and Bax. Pancratistatin induced arrest of HCT-15 cells at G2/M of the cell cycle and inhibited phosphorylation of cdc2/cyclin-dependent kinase 1 (CDK1) and Cdc25c and the expression of cyclin B1. CONCLUSIONS Pancratistatin inhibited the growth of colorectal cancer cells in vitro by inducing apoptosis, autophagy, and G2/M cell cycle arrest.

A short deletion in the DNA-binding domain of STAT3 suppresses growth and progression of colon cancer cells.

In this study, we investigated the effect of a short deletion in the DNA-binding domain of STAT3 (STAT3del) on the transcriptional activation of STAT3 target genes and its relationship with colon carcinogenesis. We used the CRISPR-CAS9 gene editing system to delete a short sequence encoding amino acids 400-411 in the DNA-binding domain (amino acid sequence: 317-567) from STAT3 gene in SW480, SW620 and HCT116 colon cancer cells. ChIP sequencing analysis showed that STAT3del occupancy was significantly reduced in 1029 genes and significantly increased in 475 genes compared to wild-type STAT3. The mutation altered the DNA motifs recognized by STAT3del as compared to the wild-type STAT3. We observed a strong correlation between expression of the STAT3 target genes and the loss or gain of STAT3del binding to their promoters. CCK-8, wound healing, and TUNEL assays showed reduced proliferation, migration, and survival of SW480, SW620 and HCT-116 cells expressing STAT3del as compared to the corresponding controls. These findings demonstrate that a short deletion in the DNA-binding domain of STAT3 alters its genome-wide DNA-binding and transcriptional profile of STAT3-target proteins, and suppresses the growth, progression and survival of colon cancer cells.