An in vitro based investigation into the cytotoxic effects of D-amino acids.
In the present study, cytotoxic effects of D-Ala, D-Pro and D-Lys are demonstrated. In an effort to study the possible mechanisms of the observed cytotoxicity, catalase activity, H2O2 generation, and apoptotic activity were measured in HeLa and MCF-7 cell lines. Although D-Lys is a poor substrate for DAO and therefore low H2O2 was detected, it was shown to provoke severe impairment of cellular integrity and survival. Interestingly, a very good substrate for DAO, such as D-Pro, did not substantially reduce cell viability. On the other hand, a moderate substrate for DAO, represented by D-Ala, was shown to moderately trigger toxicity in the tested cell lines. Although a correlation between the in vitro cytotoxicity of D-amino acids and the amount of H2O2 produced was absent, there was a good agreement between the ability of D-amino acids to trigger apoptosis and to provoke toxicity. Our results indicate that the toxicity of D-amino acids does not appear to be solely mediated by H2O2. Therefore, we hypothesize that other possible contributing apoptosis-mediated pathways might cause the observed toxicity.
Sanaa K
SK
Bardaweel
Rana
R
Abu-Dahab
Nour F
NF
Almomani
D000409:Alanine / Q000737:chemistry / Q000494:pharmacology*; D000596:Amino Acids / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008239:Lysine / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D011392:Proline / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
D000596:Amino Acids; D000970:Antineoplastic Agents; D011392:Proline; D006861:Hydrogen Peroxide; D008239:Lysine; D000409:Alanine