Proapoptotic activity and ABCC1-related multidrug resistance reduction ability of semisynthetic oleanolic acid derivatives DIOXOL and HIMOXOL in human acute promyelocytic leukemia cells.
作者： A. Paszel-Jaworska , B. Rubiś , B. Bednarczyk-Cwynar , L. Zaprutko , M. Rybczyńska
DOI: 10.1016/J.CBI.2015.07.011
关键词:
摘要: One of the main problems present-day oncology is ability neoplastic cells to develop different mechanisms resistance chemotherapeutic agent. A natural compound oleanolic acid (OA) was found be active against many types cells. This paper examines influence eight semisynthetic derivatives on drug-sensitive human acute promyelocytic leukemia cell line HL-60 and its multidrug resistant subline ABCC1 overexpressing HL-60/AR. Viability inhibition, proapoptotic activity, as well gene expression level, inhibit transport function associated protein 1 (ABCC1) alter level by tested compounds, were evaluated. The most potent compounds DIOXOL (methyl 3,11-dioxoolean-12-en-28-oate) HIMOXOL 3-hydroxyimino-11-oxoolean-12-en-28-oate). efficient in inducing apoptosis It activated both intrinsic extrinsic pathways apoptotic death. Proapoptotic properties probably related significant decrease p65 NFκB inhibition translocation nucleus. In turn, HL-60/AR inhibited (short time response) decreased (long a result reduction expression.
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