Next Article in Journal
Lactation Affects Isolated Mitochondria and Its Fatty Acid Composition but Has No Effect on Tissue Protein Oxidation, Lipid Peroxidation or DNA-Damage in Laboratory Mice
Previous Article in Journal
Which Is the Most Significant Cause of Aging?
Article Menu

Export Article

Open AccessArticle
Antioxidants 2016, 5(1), 1;

Effects of Antioxidants in Human Cancers: Differential Effects on Non-Coding Intronic RNA Expression

Skyline High School, Ann Arbor, MI-48103, USA
Department of Pediatrics, University of Michigan, Ann Arbor, MI-48109, USA
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI-48109, USA
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI-48109, USA
Author to whom correspondence should be addressed.
Academic Editor: David Burritt
Received: 26 August 2015 / Revised: 16 November 2015 / Accepted: 25 November 2015 / Published: 4 January 2016
Full-Text   |   PDF [1506 KB, uploaded 4 January 2016]   |  


The notion that dietary antioxidants can help fight cancer is popular. However, the mechanism(s) behind the effect of antioxidants in cancer is still unclear. Previous studies indicate that supplements can influence gene expression; however, all of these studies were focused on the coding/exonic gene expression. Studies are now emerging to highlight critical functional roles for RNAs expressed from the non-coding regions. This project was designed to study the effect of antioxidant supplements on non-coding intronic RNA expression in human cancers. Vitamin E, N-Acetyl cysteine (NAC) and Sulforaphane are commonly used supplements to prevent diseases including cancers. We studied the effect of these antioxidant supplements on the non-coding intronic RNA expression using publicly available datasets from a mouse model for lung cancer and prostate cancer cell lines. Although high throughput polyA-enriched RNA-Seq data characterize spliced coding mRNA regions, recent studies reveal the expression of reads from the non-coding intronic regions. Our analyses indicate that cancer cells have higher expression of introns compared to that of normal cells and that treatment with antioxidant supplements reduces the increased expression of introns of several genes. However, we did find high expression of introns of multiple genes including many oncogenes in the supplement treated groups compared to that of the control; this effect was distinct depending on the cell type and the supplement studied. Using RT-PCRs, we validated the expression of introns of two oncogenes, DLK1 and LRG1, known to be key players in lung cancer progression, and demonstrate changed intronic expression with supplement treatment in cancer cells. With regard to the antioxidant system, supplements did not change the intronic RNAs for endogenous antioxidant enzymes except for a significant decrease in the expression of superoxide dismutase (SOD) intronic RNA. Concurrently, we also found that a prolonged (48 h) exposure to Vitamin C, Vitamin E and Green tea extract reduced the enzymatic activity of SOD in lung cancer cells. The results from this study reveal that the antioxidant supplements have a significant effect on the intronic RNA expression of many genes including cancer genes that are not directly linked to the body’s antioxidant system. It is important to study this novel effect of antioxidant supplements in detail as it may have a significant role in disease progression. View Full-Text
Keywords: antioxidants; intronic RNA; lung cancer; prostate cancer antioxidants; intronic RNA; lung cancer; prostate cancer

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Menon, S.; Lu, C.; Menon, R.; Schwartz, J.; Guan, Y. Effects of Antioxidants in Human Cancers: Differential Effects on Non-Coding Intronic RNA Expression. Antioxidants 2016, 5, 1.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Antioxidants EISSN 2076-3921 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top