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. 2024 Aug 26;38(11):2395–2409. doi: 10.1038/s41375-024-02390-9

Fig. 7. Lipotoxicity increases DNA damage and sensitizes SSI-4 treated cells to DNA-damage-inducing chemotherapy both in vitro and in vivo.

Fig. 7

A, B Representative western blots (n = 3) of MV-4-11 cells treated with SSI-4 (1 µM) or vehicle control with or without the addition of oleate (100 µM), palmitate (100 µM) or doxorubicin (1 µM) for 24 h. C MV-4-11 non-targeting (NT) gRNA, SCD gRNA 1, and SCD gRNA 2 were treated for 72 h with doxorubicin (1 µM). Cell death induction was determined by Annexin-V expression. D MV-4-11 and leukemic iMLL-AF9 cells were treated for 72 h with growing concentrations of SSI-4 and doxorubicin. Synergy was determined by the Bliss coefficient (ZIP Score > 10 indicates synergism). Viable cells were determined as Annexin-V-/Zombie-. E CD45.2+ leukemic iMLL-AF9 cells were transplanted into CD45.1+ NBSGW mice (n = 18). When leukemic burden in PB reached 20%, animals were treated for 7 days with 10 mg/kg SSI-4 or corresponding vehicle orally with or without conventional chemotherapy protocol. The dotted line represents the start of treatment. Kaplan–Meier curve represents the overall survival of animals treated with SSI-4 and corresponding vehicle with our without conventional chemotherapy. Data are mean ± SD. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.