Novel antioxidants are not toxic to normal tissues but effectively kill cancer cells

Abstract

Free radicals are formed as a result of cellular processes and play a key role in predisposition to and development of numerous diseases and of premature aging. Recently, we reported the syntheses of a number of novel phenolic antioxidants for possible application in food industry. In the present study, analyses of the cellular processes and molecular gene expression effects of some of the novel antioxidants in normal human tissues and in cancer cells were undertaken. Results indicated that whereas the examined antioxidants showed no effects on morphology and gene expression of normal human oral and gingival epithelial tissues, they exerted a profound cell killing effect on breast cancer cells, including on chemotherapy-resistant breast cancer cells and on oral squamous carcinoma cells. Among the tested antioxidants, N-decyl-N-(3-methoxy-4-hydroxybenzyl)-3-(3,4-dihydroxyphenyl) propanamide and N-decyl-N-(3,5-dimethoxy-4-hydroxybenzyl)-3-(3,4-dihydroxyphenyl) propanamide were the most promising, with excellent potential for cancer treatment. Moreover, our gene expression databases can be used as a roadmap for future analysis of mechanisms of antioxidant action.

Keywords: :

• free radicals
• antioxidants
• gene expression
• human 3D tissues
• breast cancer
• oral cancer

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We are grateful to Jody Filkowski for running the Illumina array expression, to Dr Vasyl Chekhun for the gift of MCF-7/DOX and MCF-7/cisDDP cells, and to Dr Joseph Dort for the gift of OSCC cell lines. Research in the Kovalchuk laboratory was supported by the Alberta Cancer Foundation, CIHR, and NSERC. Research in the Przybylski laboratory was supported by the Alberta Funding Consortium and the Alberta Value Added Corporation.