Nutrient and antioxidant modulation of apoptosis in gastric and colon cancer cells.
Gastric cancer and colon cancer are major causes of mortality and morbidity worldwide. Many cancers manifest due to changes in gene expression, particularly those involved in cellular proliferation and apoptosis. Apoptosis is an important process that removes damaged or deleterious cells and contributes to normal cellular and tissue homeostasis. Apoptosis is a tightly regulated process mediated by caspases, and the involvement of the Bcl-2 superfamily of membrane bound proteins, among others. Thus, the therapeutic induction of apoptosis has been proposed as a novel method to eliminate cancer cells. The oxidative pentose pathway (OPP) and the glutathione (GSH) antioxidant defense system play an important role in the regulation of cell growth and apoptosis. The OPP regulates intracellular redox status and provides NADPH for the synthesis of GSH, an important antioxidant. GSH is required to inactivate intracellular reactive oxygen species (ROS) which induce apoptosis and cell injury. Depletion of GSH increases the sensitivity of cells to ROS. Many chemotherapeutic agents induce apoptosis through ROS-mediated cell damage. Therefore, we speculate that the therapeutic inhibition of the OPP and/or the GSH defense system may increase the sensitivity of gastric and colon cancer cells to anti-cancer therapy. Moreover, we hypothesize that the short-chain fatty acid, butyrate, will induce apoptosis in gastric cancer cells and, secondly, that differences in butyrate metabolism will exist between these cancer cell lines.
Matthews
Geoffrey M
GM
Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women's Health Service, North Adelaide, SA, Australia. geoffrey001@hotmail.com
Howarth
Gordon S
GS
Butler
Ross N
RN
D000975:Antioxidants / Q000502:physiology*; D017209:Apoptosis; D003110:Colonic Neoplasms / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D015596:Nutrition Assessment; D013274:Stomach Neoplasms / Q000473:pathology / Q000503:physiopathology*
D000975:Antioxidants