학술논문

THE ANTIMALARIA DRUG ARTEMISININ DISPLAYS STRONG CYTOTOXIC EFFECT ON LEUKAEMIA LYMPHOCYTES IN COMBINATION WITH VITAMIN C AND PRO-VITAMIN K3.
Document Type
Article
Source
Bulgarian Journal of Veterinary Medicine. Dec2021, Vol. 24 Issue 4, p533-543. 11p.
Subject
*ARTEMISININ
*ANTINEOPLASTIC agents
*CELL death
*CELLULAR signal transduction
*OXIDATION-reduction reaction
*HABER-Weiss reaction
*VITAMIN C
Language
ISSN
1311-1477
Abstract
This study investigated the anticancer effect of the anti-parasitic drug artemisinin in combination with two redox modulators: vitamin C and pro-vitamin K3 (C/K3) The experiments were conducted on leukaemia cells Jurkat. Cells were treated with either artemisinin or C/K3 alone and with all three compounds. Cell proliferation and viability were analysed using trypan blue stating and automated cell counting. The results showed that artemisinin (>10 μM) suppressed cell proliferation activity, but did not induce cell death up to 500 μM. The drug demonstrated a clear cytostatic effect at concentrations 250μ 500 μM - Jurkat cells did not proliferate, but were alive. The combination C/K3 (200:2, 300:3 μM/μM) applied alone did not affect cell proliferation and viability. Vitamins C/K3 in concentration ratio 500:5 (µM/μM) decreased cell proliferation activity by ~10%. The triple combination artemisinin/C/K3 manifested synergistic anti-proliferative effects at all concentration ratios analysed. This synergistic effect increased with increasing C/K3 concentration. Based on literature data, it was assumed that the anti-proliferative effect of the triple combination was mediated by changes in the redox-homeostasis of cancer cells. The C/K3 redox system likely acted on cancer mitochondria and increased superoxide production and activation of pro-apoptotic signals, specific for cancer cells. On the other hand, artemisinin could generate hydroxyl radicals as a result of activation of Fenton reactions, depleting intracellular reducing equivalents. Both redox mechanisms lead to activation of signal pathways for induction of cancer cell death. [ABSTRACT FROM AUTHOR]