Antitumor effects of a natural anthracycline analog (Aloin) involve altered activity of antioxidant enzymes in HeLaS3 cells.
The antiproliferative and cytotoxic potential of the natural anthracycline aloin from Aloe vera was tested on human uterine carcinoma HeLaS3 cells. Aloin showed a pronounced antiproliferative effect at physiological concentration (IC50 = 97 microM), caused cell cycle arrest in the S phase and markedly increased HeLaS3 cell apoptosis (to 24%). In the concentration range of 20-100 microM, its action was accompanied by remarkable changes in the activity of almost all antioxidant enzymes: MnSOD activity was increased many fold, while CuZnSOD and iNOS activities were inhibited. Moreover, inhibition of CuZnSOD was shown to occur by direct aloin interaction with the enzyme. As catalase activity was not changed, it is suggested that such conditions were responsible for antiproliferative and cytotoxic effects owing to accumulation of H2O2. Aloin alone was a more potent proapoptotic agent than a 2 Gy fractional dose of ionizing radiation or a combination of the two. Compared to other currently used therapeutics, aloin, due to its less undesirable side effects and antimetastatic potential, may prove to be the agent of choice on which clinical protocols for the treatment of human cervical carcinoma should rely in future.
Nićiforović
Ana
A
Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, Belgrade, Serbia.
Adzić
Miroslav
M
Spasić
Snezana D
SD
Radojcić
Marija B
MB
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002277:Carcinoma / Q000201:enzymology*; D002453:Cell Cycle; D049109:Cell Proliferation; D004642:Emodin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006367:HeLa Cells; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects / Q000528:radiation effects; D010088:Oxidoreductases / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000201:enzymology*
D000970:Antineoplastic Agents; D016328:NF-kappa B; D010088:Oxidoreductases; D004642:Emodin; C006457:alloin