Abstract
Background: One of the most important strategies in research and development of new anticancer agents is the tumor-specific induction of apoptosis. The effects of semisynthetic derivative of vitamin E, (?-TOS, D-?-tocopheryl succinate), appear to be largely restricted to malignant cells. Methods: We investigated the in vivo effects of intraperitoneally administered ?-TOS on vitality of Ehrlich ascites carcinoma cells (EAC) in mice, as well as the influence of ?-TOS on specific activity of enzymes involved in antioxidative mechanisms in EAC cells. Results: According to our results, the intraperitoneal application of ?-TOS induces the decrease of the EAC vitality, and the statistically significant alteration of the glutathione-dependent enzyme activity in EAC cells. Conclusion: We may conclude that ?-TOS is an important micronutrient, with significant impact on vitality and metabolism of malignant cells.
Highlights
The most important feature of an anti-cancer agent, preventing progression of the malignant disease, is to selectively control and prevent tumor growth, exerting low toxicity towards normal cells
We investigated the in vivo effects of intraperitoneally administered α-TOS on vitality of Ehrlich ascites carcinoma 1Department of Biochemistry, Medical cells (EAC) in mice, as well as the influence of α-TOS on specific activity of enzymes involved in antioxidative mechanisms in Faculty Novi Sad, Hajduk Veljkova 3, EAC cells
We studied the in vivo effects of α-TOS on Ehrlich ascites carcinoma (EAC) cells vitality and activity of enzymes involved in reactive oxygen species (ROS) attenuation
Summary
The most important feature of an anti-cancer agent, preventing progression of the malignant disease, is to selectively control and prevent tumor growth, exerting low toxicity towards normal cells. Recent study of Weber et al [15], have shown that the high sensitivity of malignant cells to α-TOS effects is based on its ability to efficiently induce the mitochondrial signal transmission mechanisms (including ROS generation), which triggers apoptosis. These authors believe that the major mode of action of α-TOS is mitochondrial destabilization, involving the formation of ROS, followed by the release of cytochrome c and activation of multiple caspases, without deregulation of tumor suppressor activity [15]. In a pre-clinical model Provisionally accepted: 08.08.2007 that the intraperitoneal (IP) injection of VE analogue into mice results in rapid Accepted: 04.10.2007 accumulation at sites distal to tumors [4]
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