Epigenetic changes and alternate promoter usage by human colon cancers for expressing DCLK1-isoforms: Clinical Implications

Current chemotherapeutics for metastatic colorectal cancers have limited success and are extremely toxic due to nonselective targeting. Some natural extracts have been traditionally taken and have shown anticancer activity. These extracts have multiple phytochemicals that can target different pathways selectively in cancer cells. We have shown previously that lemongrass ( Cymbopogon citratus) extract is effective at inducing cell death in human lymphomas. However, the efficacy of lemongrass extract on human colorectal cancer has not been investigated. Furthermore, its interactions with current chemotherapies for colon cancer is unknown. In this article, we report the anticancer effects of ethanolic lemongrass extract in colorectal cancer models, and importantly, its interactions with FOLFOX and Taxol. Lemongrass extract induced apoptosis in colon cancer cells in a time and dose-dependent manner without harming healthy cells in vitro. Oral administration of lemongrass extract was well tolerated and effective at inhibiting colon cancer xenograft growth in mice. It enhanced the anticancer efficacy of FOLFOX and, interestingly, inhibited FOLFOX-related weight loss in animals given the combination treatment. Furthermore, feeding lemongrass extract to APCmin/+ transgenic mice led to the reduction of intestinal tumors, indicating its preventative potential. Therefore, this natural extract has potential to be developed as a supplemental treatment for colorectal cancer.

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Human Protein Tyrosine Phosphatase 1C (PTPN6) Gene Structure: Alternate Promoter Usage and Exon Skipping Generate Multiple Transcripts

Genomics ◽

10.1006/geno.1995.1020 ◽

1995 ◽

Vol 27 (1) ◽

pp. 165-173 ◽

Cited By ~ 78

Author(s):

Denis Banville ◽

Rino Stocco ◽

Shi-Hsiang Shen

Keyword(s):

Gene Structure ◽

Protein Tyrosine Phosphatase ◽

Tyrosine Phosphatase ◽

Exon Skipping ◽

Human Protein ◽

Protein Tyrosine ◽

Multiple Transcripts ◽

Alternate Promoter ◽

Promoter Usage

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Chemical Synthesis ofEscherichia ColiSThAnalogues by Regioselective Disulfide Bond Formation: Biological Evaluation of an111In-DOTA−Phe19-SThAnalogue for Specific Targeting of Human Colon Cancers

Bioconjugate Chemistry ◽

10.1021/bc010062u ◽

2002 ◽

Vol 13 (2) ◽

pp. 224-231 ◽

Cited By ~ 20

Author(s):

Hariprasad Gali ◽

Gary L. Sieckman ◽

Timothy J. Hoffman ◽

Nellie K. Owen ◽

Dana G. Mazuru ◽

...

Keyword(s):

Chemical Synthesis ◽

Disulfide Bond ◽

Bond Formation ◽

Human Colon ◽

Biological Evaluation ◽

Disulfide Bond Formation ◽

Specific Targeting ◽

Colon Cancers

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O-GlcNAcylation of PGK1 coordinates glycolysis and TCA cycle to promote tumor growth

Nature Communications ◽

10.1038/s41467-019-13601-8 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 10

Author(s):

Hao Nie ◽

Haixing Ju ◽

Jiayi Fan ◽

Xiaoliu Shi ◽

Yaxian Cheng ◽

...

Keyword(s):

Tumor Growth ◽

Cancer Cells ◽

Tumor Development ◽

Lactate Production ◽

Phosphoglycerate Kinase ◽

Tca Cycle ◽

Human Colon ◽

Colon Cancers ◽

The Tca Cycle ◽

Promote Tumor Growth

AbstractMany cancer cells display enhanced glycolysis and suppressed mitochondrial metabolism. This phenomenon, known as the Warburg effect, is critical for tumor development. However, how cancer cells coordinate glucose metabolism through glycolysis and the mitochondrial tricarboxylic acid (TCA) cycle is largely unknown. We demonstrate here that phosphoglycerate kinase 1 (PGK1), the first ATP-producing enzyme in glycolysis, is reversibly and dynamically modified with O-linked N-acetylglucosamine (O-GlcNAc) at threonine 255 (T255). O-GlcNAcylation activates PGK1 activity to enhance lactate production, and simultaneously induces PGK1 translocation into mitochondria. Inside mitochondria, PGK1 acts as a kinase to inhibit pyruvate dehydrogenase (PDH) complex to reduce oxidative phosphorylation. Blocking T255 O-GlcNAcylation of PGK1 decreases colon cancer cell proliferation, suppresses glycolysis, enhances the TCA cycle, and inhibits tumor growth in xenograft models. Furthermore, PGK1 O-GlcNAcylation levels are elevated in human colon cancers. This study highlights O-GlcNAcylation as an important signal for coordinating glycolysis and the TCA cycle to promote tumorigenesis.

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