Figure 2.

PRMT5 inhibition decreases global cellular SDMA methylation and attenuates cell cycle and viability of cancer cell lines. (A) Representative SDMA dose-response curve (total SDMA normalized to SMD3) following 3 days of compound treatment. (B) Growth IC₅₀ (6 days treatment) in comparison to SDMA EC₅₀ and percent decrease in SDMA (maximum minus minimum at concentrations evaluated) in a panel of MCL cell lines (3 days treatment with GSK3326595). (C) Representative cell cycle histogram of Z-138 cells treated with 0 or 200 nM GSK3326595 for 3 days. Propidium iodide stained nuclei were evaluated by flow cytometry. (D) Cell cycle distribution of Z-138 cells treated with 30, 200 and 1,000 nM GSK3326595 for 1, 2, 3, 5, 7, or 10 days. ND, not determined. (E) Cell cycle distribution of a panel of MCL cell lines treated with 40, 200, 1,000, and 5,000 nM GSK3326595 for 3 days. (F) Cell cycle distribution of breast cancer cell lines treated with 30, 200, and 1,000 nM GSK3326595 for 2, 7, or 10 days. (G) Representative plot of early apoptosis (Annexin V) and cell death (7AAD) markers comparing cells treated with DMSO and cells treated with 200 nM GSK3326595 by flow cytometry. (H) Annexin V and 7AAD staining of MCL cell lines treated with 40 nM, 200 nM, 1,000 nM or 5,000 nM GSK3326595 for 3 or 6 days.