FIGURE 4 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors
Year: 2023
Type: other
Abstract: Pitavastatin is three times more potent than simvastatin in cell-based assays of apoptosis and biomarker responses, and increases apoptosis in combination with venetoclax in a subset of patient samples treated ex vivo. A, Cell Titer Glo was used to assess viability in statin/BH3 mimetic combinations after 48 hours; % viable cells was normalized to vehicle. Mean ± SD, n = 3. B, Pitavastatin increases PUMA and blocks prenylation of RAP1A at concentrations lower than simvastatin. C, Results of a glucocorticoid resistance cell line models MM.1S (sensitive) and MM.1R (resistant) after 48 hours treatment. Mean ± SD; n = 3; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001, one-way ANOVA with Tukey post-test correction for multiple comparisons. D, Buffy coats from multiple myeloma patient bone marrow aspirates were treated in vitro with 1 µmol/L pitavastatin and 10 nmol/L venetoclax for 24 hours before staining with CD45, CD38, and Annexin V to assess viability.
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: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4389478306