Chloroquine aggravates the arsenic trioxide (As2O3)-induced apoptosis of acute promyelocytic leukemia NB4 cells via inhibiting lysosomal degradation in vitro
D.-M. Liu, X.-D. Zhang, L. Yang Department of Hematology, Laiyang Central Hospital, Yantai, Shandong Province, China. yangling84vid@163.com
OBJECTIVE: Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML), as standing out for its distinguished sensitivity to all-trans retinoic acid and arsenic trioxide (ATO, As2O3). The As2O3-mediated degradation of PML-RARA (promyelocytic leukemia-retinoic acid receptor-α) oncoprotein via the proteasome pathway appears to be critical for such distinguished sensitivity.
MATERIALS AND METHODS: The present study was to evaluate the influence by chloroquine (CQ), an inhibitor to the release of lysosomal enzymes, on the sensitivity of APL cells to As2O3. APL-derived NB4 cell line was treated with As2O3 or/and CQ in vitro. Then, the cell viability, the induction of apoptosis, and autophagy were examined with MTT assay, with TUNEL staining or with enhanced green fluorescence protein (EGFP)-light Chain 3 (LC3) reporter. The apoptosis- or autophagy-associated proteins were quantified with Western blotting assay.
RESULTS: Our results demonstrated that the As2O3 treatment promoted either apoptosis or autophagy in APL NB4 cells and upregulated both apoptosis- and autophagy-associated proteins. However, additional CQ treatment deteriorated the As2O3-induced NB4 cell apoptosis, whereas aggravated the As2O3-induced accumulation of acidic vesicular organelles (AVOs) and blocked the lysosomal degradation in NB4 cells.
CONCLUSIONS: Chloroquine aggravates the arsenic trioxide-induced apoptosis of APL NB4 cells via inhibiting lysosomal degradation in vitro. It implies that chloroquine might be adjuvant to sensitize APL cells to arsenic trioxide.
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To cite this article
D.-M. Liu, X.-D. Zhang, L. Yang
Chloroquine aggravates the arsenic trioxide (As2O3)-induced apoptosis of acute promyelocytic leukemia NB4 cells via inhibiting lysosomal degradation in vitro
Eur Rev Med Pharmacol Sci
Year: 2018
Vol. 22 - N. 19
Pages: 6412-6421
DOI: 10.26355/eurrev_201810_16054