Table 2.

Median dose effect analysis was also employed to characterize the interactions between DHMEQ and TMZ. For concomitant treatment, different doses of DHMEQ were combined with 250 μM TMZ and treated for 48 h. For the sequential schedule cells were exposed to different concentrations of DHMEQ, and after 6 h TMZ at the same dose was included in culture media and also analyzed at 48 h (TMZ exposure 42 h). Combination index (CI) values <1 correspond to a synergistic interaction (emphasized in bold). Dose reduction index (DRI) reflects the fold reduction in the required concentration of tested agents when used in combination to achieve the comparable affected fraction (AF).

U251		Concomitant TMZ (250 μM)			Sequential TMZ (250 μM)
DHMEQ (μg/mL)	AF	AF	CI	DRI	AF	CI	DRI
2.5	0.00	0.15	2.02	0.58	0.38	0.68	1.87
5	0.07	0.26	1.31	1.11	0.42	0.73	2.19
10	0.19	0.36	1.21	1.73	0.6	0.59	4.36
20	0.47	0.65	0.83	5.33	0.8	0.51	10.99
U343MG-a		Concomitant TMZ (250 μM)			Sequential TMZ (250 μM)
DHMEQ (μg/mL)	AF	AF	CI	DRI	AF	CI	DRI
2.5	0.08	0.37	0.8	1.56	0.26	1.17	1.08
5	0.10	0.44	0.78	1.92	0.41	0.86	1.76
10	0.22	0.58	0.69	2.86	0.58	0.69	2.86
20	0.53	0.79	0.47	5.84	0.80	0.45	6.10
U138MG		Concomitant TMZ (250 μM)			Sequential TMZ (250 μM)
DHMEQ (μg/mL)	AF	AF	CI	DRI	AF	CI	DRI
2.5	0.01	0.01	4.22	0.31	0.18	0.48	2.07
5	0.01	0.01	2.08	0.48	0.26	0.36	2.76
10	0.03	0.02	1.60	0.62	0.34	0.28	3.50
20	0.02	0.02	1.10	3.03	0.85	0.06	15.25
U87MG		Concomitant TMZ (250 μM)			Sequential TMZ (250 μM)
DHMEQ (μg/mL)	AF	AF	CI	DRI	AF	CI	DRI
2.5	0.00	0.53	0.3	7.1	0.42	0.61	2.42
5	0.10	0.45	0.68	3.26	0.61	0.34	15.71
10	0.27	0.60	0.64	14.2	0.83	0.33	248.40
20	0.69	0.88	0.55	666.16	0.94	0.38	4197.79
T98G		Concomitant TMZ (250 μM)			Sequential TMZ (250 μM)
DHMEQ (μg/mL)	AF	AF	CI	DRI	AF	CI	DRI
2.5	0.05	0.02	53.87	0.01	0.26	1.00	1.20
5	0.11	0.08	7.58	0.15	0.36	0.70	2.39
10	0.18	0.13	4.52	0.6	0.39	0.85	2.88
20	0.43	0.32	1.84	0.76	0.82	0.22	50.10
LN319		Concomitant TMZ (250 μM)			Sequential TMZ (250 μM)
DHMEQ (μg/mL)	AF	AF	CI	DRI	AF	CI	DRI
2.5	0.09	0.41	0.37	4.37	0.44	0.33	5.1
5	0.25	0.55	0.3	8.90	0.34	0.68	2.74
10	0.44	0.7	0.27	20.09	0.89	0.09	96.11
20	0.67	0.8	0.31	39.6	0.88	0.19	84.93