Tilaoui Mounir, Mouse Hassan Ait, Jaafari Abdeslam, Zyad Abdelmajid
Laboratory of Biological Engineering, Natural Substances, Cellular and Molecular Immuno-pharmacology, Immunobiology of Cancer Cells Cluster, Faculty of Science and Technology, P. Box 523, 23000 Béni-Mellal, Morocco.
Nat Prod Bioprospect. 2014 Jun;4(3):189-96. doi: 10.1007/s13659-014-0024-4. Epub 2014 Jun 5.
The present study aims at defining the differential cytotoxicity effect of artemisinin toward P815 (murin mastocytoma) and BSR (kidney adenocarcinoma of hamster) cell lines. Cytotoxicity was measured by the growth inhibition using MTT assay. These in vitro cytotoxicity studies were complemented by the determination of apoptotic DNA fragmentation and Annexin V- streptavidin-FITC assay. Furthermore, we examined the in vitro synergism between artemisinin and the chemotherapeutic drug, vincristin. The in vivo study was investigated using the DBA2/P815 (H2d) mouse model. While artemisinin acted on both tumor cell lines, P815 was much more sensitive to this drug than BSR cells, as revealed by the respective IC50 values (12 µM for P815 and 52 µM for BSR cells). On another hand, and interestingly, apoptosis was induced in P815 but not induced in BSR. These data, reveal an interesting differential cytotoxic effect, suggesting the existence of different molecular interactions between artemisinin and the studied cell lines. In vivo, our results clearly showed that the oral administration of artemisinin inhibited solid tumor development. Our study demonstrates that artemisinin caused differential cytotoxic effects depending not only on the concentration and time of exposure but also on the target cells.
本研究旨在确定青蒿素对P815（鼠肥大细胞瘤）和BSR（仓鼠肾腺癌）细胞系的细胞毒性差异。通过MTT法检测生长抑制来测定细胞毒性。这些体外细胞毒性研究通过测定凋亡DNA片段化和膜联蛋白V-链霉亲和素-FITC检测进行补充。此外，我们研究了青蒿素与化疗药物长春新碱之间的体外协同作用。使用DBA2/P815（H2d）小鼠模型进行体内研究。虽然青蒿素对两种肿瘤细胞系都有作用，但如各自的IC50值所示（P815为12μM，BSR细胞为52μM），P815对该药物比BSR细胞更敏感。另一方面，有趣的是，P815诱导了凋亡而BSR未诱导凋亡。这些数据揭示了一种有趣的细胞毒性差异效应，表明青蒿素与所研究的细胞系之间存在不同的分子相互作用。在体内，我们的结果清楚地表明口服青蒿素可抑制实体瘤的发展。我们的研究表明，青蒿素产生的细胞毒性差异不仅取决于暴露的浓度和时间，还取决于靶细胞。
