Journal Article

Ascorbic acid suppresses drug-induced apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions

Uwe Wenzel, Alexander Nickel, Sabine Kuntz and Hannelore Daniel

in Carcinogenesis

Volume 25, issue 5, pages 703-712
Published in print May 2004 | ISSN: 0143-3334
Published online May 2004 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgh079
Ascorbic acid suppresses drug-induced apoptosis in human colon cancer cells by scavenging mitochondrial superoxide anions

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Although a high alimentary intake of antioxidant vitamins such as ascorbic acid may play an important role in cancer prevention, a high level of antioxidants may have quite different effects at different stages of the transformation process. In cancer development, the resistance of cells to apoptosis is one of the most crucial steps. We have tested the effects of ascorbic acid on apoptosis in HT-29 human colon carcinoma cells when induced by two potent apoptosis inducers, the classical antitumor drug camptothecin or the flavonoid flavone. Apoptosis was assessed based on caspase-3-like activity, plasma membrane disintegration and finally nuclear fragmentation and chromatin condensation. Ascorbic acid dose-dependently inhibited the apoptotic response of cells to camptothecin and flavone. RT–PCR analysis and western blot analysis revealed that ascorbic acid specifically blocked the decrease of bcl-XL by camptothecin or flavone. An increased generation of mitochondrial [math] precedes the down-regulation of bcl-XL by camptothecin and flavone and ascorbic acid at a concentration of 1 mM prevented the generation of this reactive oxygen species. In conclusion, ascorbic acid functions as a potent antioxidant in mitochondria of human colon cancer cells and thereby blocks drug-mediated apoptosis induction allowing cancer cells to become insensitive to chemotherapeutics.

Keywords: COX-2, cyclooxygenase-2; GAP-DH, glyceraldehyde-3-phosphate dehydrogenase; RT–PCR, reverse transcriptase–polymerase chain reaction

Journal Article.  5671 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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