Fig. 6.

H₂S-releasing doxorubicin triggers ER-dependent pro-apoptotic pathways in resistant osteosarcoma cells. a Hitmap of unfolded protein response (UPR)-related genes in U-2OS and U-2OS/DX580 cells, after 24 h treatment with drug-free medium, 5 µM doxorubicin (dox) or H₂S-releasing doxorubicin (Sdox). The figure reports genes up- or down-regulated at least twofold, in at least one cell line, compared to untreated U-2OS cells (n = 6 independent experiments). The expression of each gene in U-2OS cells was considered 1 (not shown). The whole list of genes analyzed is reported in Supplementary Tables 3, 4 (Online Resources 9, 10). b Cells treated as in a were lysed and probed with the indicated antibodies. The β-tubulin expression was used as control of equal protein loading. The figure is representative of one out of four experiments. XBP1(u): un-spliced; XBP1(s): spliced. c CHOP amount measured in nuclear extracts of cells treated as reported in a. The TBP expression was used as control of equal protein loading. The figure is representative of one out of four experiments. d Whole cell lysates from cells treated as indicated in a were probed with the indicated antibodies. The β-tubulin expression was used as control of equal protein loading. The figure is representative of one out of four experiments. ctrl drug-free medium