MitoNEET (CISD1) is a mitochondrial outer membrane protein that plays a critical role in maintaining mitochondrial homeostasis and is frequently overexpressed in cancer. NL-1, derived from pioglitazone, is a mitoNEET inhibitor with antileukemic activity. Treatment with NL-1 reduced the number of viable cells in both REH and REH/Ara-C cell lines in a concentration-dependent manner. The IC50 value of NL-1 was comparable in REH (47.35 ± 7.7 μM) and REH/Ara-C (56.26 ± 8.8 μM) cells. Furthermore, the NL-1 treatment (60 μM; 72 hours) consistently reduced the size and number of preformed SD1 spheroids in SD1 ALL cells. Additionally, both the number of live cells and the percentage of viability of the cells was reduced when treated with NL-1. NL-1 pretreatment inhibited the chemotactic ability of both REH and REH/Ara-C cells to migrate toward multiple chemoattractants. The cells treated with NL-1 showed a dose-dependent decrease in chemotaxis in both cells. Treatment of BMSC and HOB cocultures with NL-1 (60 μM) decreased the number of live cells recovered from the S and PD cell populations and decreased viability of the PD population. Further, treatment with NL-1 (60 μM; 6 hours) increased the fluorescence intensity compared with untreated cells, indicating an increase in autophagy. In mice, the NL-1–treated group (1 mg/kg per day) showed significantly lower tumor burden than the control vehicle–treated group on day 14 postinjection[1].
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