HDM2 antagonist MI-219 (spiro-oxindole), but not Nutlin-3 (cis-imidazoline), regulates p53 through enhanced HDM2 autoubiquitination and degradation in human malignant B-cell lymphomas

Table 2 Summary of Annexin positive cells in wtp-53 lymphoma cell lines exposed to HDM2-SMIs

Cell line	Time (h)	Conc. (μM)	Nutlin-3	MI-219	ANOVA p^a	Post-hoc p^b
WSU-FSCCL	12 h	0	5.3 ± 0.7	5.3 ± 0.7	p = <0.001	--
		2.5	7.0 ± 2.5	13.7 ± 1.3		p = <0.001
		5.0	8.8 ± 2.0	23.8 ± 2.8		p = <0.001
		10.0	10.6 ± 1.7	36.1 ± 2.3		p = <0.001
	24 h	0	6.2 ± 0.7	6.0 ± 0.7	p = <0.0001	--
		2.5	9.6 ± 1.6	27.6 ± 8.2		NS
		5.0	12.3 ± 2.4	43.0 ± 18.6		p = <0.01
		10.0	17.3 ± 4.9	69.7 ± 6.6		p = <0.001
	48 h	0	6.1 ± 1.2	6.1 ± 1.2	p = <0.0001	--
		2.5	10.1 ± 0.7	19.5 ± 1.0		NS
		5.0	12.6 ± 1.9	35.6 ± 7.6		p = <0.001
		10.0	16.5 ± 2.6	74.5 ± 4.9		p = <0.001
KM-H2	12 h	0	7.9 ± 1.2	7.9 ± 1.2	p = 0.026	--
		2.5	11.2 ± 1.6	12.5 ± 1.3		NS
		5.0	11.8 ± 1.5	13.5 ± 0.6		NS
		10.0	13.6 ± 2.4	14.8 ± 2.9		NS
	24 h	0	8.9 ± 1.7	8.9 ± 1.7	p = 0.026	--
		2.5	11.2 ± 3.0	14.2 ± 2.5		NS
		5.0	14.5 ± 3.0	19.9 ± 3.5		NS
		10.0	20.1 ± 3.8	27.9 ± 4.8		p = 0.05
	48 h	0	2.8 ± 2.5	12.8 ± 2.5	NS
		2.5	15.9 ± 6.5	19.7 ± 9.4
		5.0	18.9 ± 8.9	23.1 ± 10
		10.0	21.1 ± 9.7	32.4 ± 9.2

^a: ANOVA for overall significance between all groups. ^b: Tukey’s post hoc comparisons between pairs (Nutlin-3 versus MI-219 at equivalent concentrations).

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