Figure 2.
Mito-HNK Inhibits the Proliferation and Tumor Growth of Lung Cancer Cells
(A) Mito-HNK and bis-Mito-HNK inhibit the proliferation of H2030 cells at significantly lower concentrations than HNK. The IC50 values were determined at the point when untreated cells reached ∼95% confluence (∼4 days of incubation).
(B) Treatment of H2030-BrM3 cells (0.1 μM, 24 hr) leads to significantly higher mitochondrial accumulation of Mito-HNK than HNK (***P < 0.001 vs. HNK).
(C) The chemical structures of Mito-HNK and the control compounds (Dec-HNK and Me-TPP+) used for data in panels D and E.
(D and E) The combinations of HNK or decyl-HNK with Me-TPP+ fail to reproduce the anti-proliferative effects of Mito-HNK. The traces recorded during real-time monitoring of cell confluence are shown in (D), and the cell confluence after 5 days of incubation with the compounds (1 μM) is shown in (E).
(F) Representative bioluminescence live imaging of NSCLC orthotopic tumor growth in control or Mito-HNK-treated mice (3.75 μmol/kg each).
(G) Quantitative data for bioluminescence imaging of the orthotropic growth of NSCLC (H2030-Br3M) cells (n = 6 per group, observation duration = 21 days).
(H) Quantitative data for the bioluminescence imaging of the orthotropic growth of SCLC (DMS-273) cells (n = 6 per group, observation duration = 15 days).
(I) Left panel, representative immunohistochemistry staining of H2030-BrM3 orthotopic lung tumors for Ki-67 in control and Mito-HNK-treated groups; right panel, quantitative estimation of cell proliferation showing percentage of Ki-67+ cells (**p < 0.01 versus control).
(J) Representative H&E staining images of H2030-BrM3 orthotopic lung tumors taken from control and Mito-HNK groups. Error bars indicate SE.