FIGURE 6 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors
Year: 2023
Type: other
Abstract: Pitavastatin-mediated activation of the ISR induces NOXA to sensitize to venetoclax separately from PUMA. Heat map summary of BCL2 family Western blot screen across all statin-sensitive cells (NCI-H929, MM.1S, L363, OPM2, MOLP8, and KMS12PE) for 16 (A) and 40 hours (B) treatments with 1 µmol/L pitavastatin. log2 transformed mean fold change of three replicates of each MMCL are plotted on a double gradient scale. C, Western blot analysis of the t(4;14) OPM2 and non-t(4;14) MM1S treated with 1 µmol/L pitavastatin or pitavastatin/ISRIB. NOXA upregulation is partially blocked by ISRIB, but PUMA is mostly ISR independent. Representative of n = 2 for tested cell lines. D, The apoptosis sensitizing effects of pitavastatin are blocked in BBC3 (PUMA) knockout L363 cell line treated with ISRIB in a 40-hour Annexin V-PI viability assay, n = 4.
Authors: Dennis Juarez, Roberta Buono, Shannon M. Matulis, Vikas A. Gupta, Madeleine Duong, Jacob Yudiono, Madhuri Paul, Sharmila Mallya, Grace Diep, Peter Hsin, Alexander Lu, Sang Mi Suh, Vy M. Dong, Andrew W. Roberts, Joel D. Leverson, Muhammad Jalaluddin, Zhuangzhuang Liu, Orlando F. Bueno, Lawrence H. Boise, David A. Fruman
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4389478283