(A) HuH6 or (B) COA67 cells were treated with 3364 or 8385 (HuH6: 8 μM, COA67: 2 μM) for 24 h and PP2A activation measured with a commercially available assay kit. There was a significant increase in PP2A activation following treatment with either compound in HuH6 and COA67 cells. (C, D) Immunoblotting was used to examine the effects of 3364 and 8385 on the endogenous inhibitors of PP2A, including CIP2A and SET. Densitometry was performed and band density reported in relation to that of the housekeeping protein. (C) There was a decrease in CIP2A expression with 3364 and 8385 treatment in HuH6 cells. SET expression did not change with either drug. (D) In COA67 cells, 3364 treatment decreased CIP2A expression, but 8385 did not affect CIP2A expression. Expression of SET was unchanged by 3364 or 8385 treatments. Experiments were repeated with at least three biologic replicates. Data reported as mean fold change ± standard error of the mean (SEM) and compared with two-tailed t-test. *p≤0.05, **p≤0.01.