Targeting leukemic side population cells by isatin derivatives of nicotinic acid amide.

Journal Article

AL-dhfyan., A.M. naglah, Z. shinwari, M.A. Bhat, M. AL-tahhan, M.A. AL-omar, A. . 2016

• نوع عمل المنشور: project
• الوسوم: side population
• المجلة \ الصحيفة: Journal of Biological Regulators & Homeostatic Agents.
• رقم العدد: 2
• رقم الإصدار السنوي: 30
• الصفحات: 353-363

مستخلص المنشور

Side population (SP) cells mediate chemoresistance in leukemia. However, chemical inhibition
approach to target SP cells has been poorly studied. Herein, we report the discovery of isatin derivatives
of nicotinic acid amide as potent side population cell inhibitors. The selected derivatives showed superior
potency over the reference drug verapamil. Furthermore, the treatment increased chemosensitivity and
inhibited the cell proliferation on three different leukemic cell lines, K562, THP-1 and U937, suggesting
that both SP and the bulk of leukemic cells are affected. Moreover, treatment with the most potent
compound Nic9 reduced the expression of ABCG2, demonstrating that side population inhibition
effect of the target derivatives is at least via ABCG2 inhibition. Importantly, the target derivatives
induced erythrocyte/dendritic differentiation to leukemic cells mainly through Musashi/Numb pathway
modulation.