FIGURE 3 from Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors
Year: 2023
Type: other
Abstract: Simvastatin induces p53-independent PUMA upregulation. A, A BCL2 family model figure depicting protein interactions and how BH3 mimetics can cooperate with apoptotic sensitizers. B, A representative Western blot analysis of statin-insensitive (red) and statin-sensitive (black) MMCLs treated for 16 hours with 10 µmol/L simvastatin. n = 3. C, Quantification by densitometry of PUMA upregulation. Mean ± SD, n = 3, significance (α<0.05) determined by one-sample t test of log-transformed fold changes against the value of 0. *, P < 0.05; **, P < 0.01. D, Representative (n = 3) Western blots showing that PUMA upregulation by 10 µmol/L simvastatin is not dependent on the transcriptional activity of p53. Expression of the p53 dominant negative, GSE56, was accomplished in three MMCLs, L363, NCI-H929, and OPM2 wherein the basal p53 status is mutated [*L363 cells have a point mutation in exon7/intron 7 splicing junction (base C782G) that impairs splicing of intron 7], wild-type, and mutated (R175H), respectively. GSE56 expression was confirmed with a rodent-specific p53 antibody (Cell Signaling Technology# 32532). Activation of p53 using 10 µmol/L of the topoisomerase inhibitor, etoposide, was used as a positive control to confirm blockade of p53 activation of PUMA upregulation.
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: W4389478282