Evidence-Based Complementary and Alternative Medicine

Research Article

Cytotoxic Constituents of the Bark of Hypericum roeperianum towards Multidrug-Resistant Cancer Cells

Table 2

Recorded IC₅₀ values following RRA for phytochemicals isolated from the bark of Hypericum roeperianum and reference drug, doxorubicin, towards drug-sensitive, MDR cancer cells lines and hepatocytes after 72 h incubation.


Cell lines	Samples, IC₅₀ values in µM, and degrees of resistance or selectivity index
Cell lines	1	3	4	5	7	8	Doxorubicin

CCRF-CEM	14.44 ± 0.53	16.80 ± 0.96	19.94 ± 2.12	38.58 ± 2.11	23.28 ± 1.46	16.31 ± 2.12	0.02 ± 0.00
CEM/ADR5000	18.27 ± 1.56	52.95 ± 3.08	23.21 ± 1.66	38.46 ± 4.07	54.04 ± 4.38	43.47 ± 2.97	122.96 ± 10.94
Degree of resistance	1.26	3.15	1.16	1.00	2.32	2.66	6,683.00
MDA-MB-231-pcDNA	16.47 ± 0.74	43.80 ± 3.47	>153.85	75.15 ± 4.88	20.73 ± 1.32	36.89 ± 2.73	0.13 ± 0.01
MDA-MB-231-BCRP	14.95 ± 1.17	33.60 ± 1.99	20.38 ± 1.17	62.94 ± 5.32	22.16 ± 2.88	30.50 ± 1.88	0.79 ± 0.08
Degree of resistance	0.91	0.77	<0.13	0.84	1.07	0.83	6.14
HCT116 (p53^+/+)	17.36 ± 1.84	46.67 ± 3.38	40.17 ± 3.09	75.48 ± 6.10	>91.74	37.79 ± 2.92	0.48 ± 0.06
HCT116 (p53⁻/⁻)	44.20 ± 3.21	>165.29	>153.85	112.27 ± 8.49	>91.74	>85.47	1.78 ± 0.08
Degree of resistance	2.55	>3.54	>6.15	1.49	nd	>2.26	3.73
U87MG	16.16 ± 1.09	74.44 ± 4.75	106.00 ± 6.74	61.42 ± 3.39	29.70 ± 1.77	35.50 ± 3.28	0.26 ± 0.03
U87MG.ΔEGFR	14.69 ± 1.55	44.98 ± 5.22	30.37 ± 2.91	59.04 ± 6.01	12.72 ± 0.75	30.61 ± 3.14	0.98 ± 0.07
Degree of resistance	0.91	0.60	0.29	0.96	0.43	0.86	3.79
HepG2	21.68 ± 3.18	44.21 ± 2.65	32.40 ± 3.72	64.73 ± 5.77	25.19 ± 1.69	31.29 ± 1.19	4.56 ± 0.48
AML12	47.34 ± 0.81	>165.29	45.35 ± 3.52	150.02 ± 7.03	20.89 ± 1.17	>85.47	52.90 ± 4.09
Selectivity index	2.18	>3.74	1.40	2.32	0.83	>2.73	11.59

(): the degree of resistance was determined as the ratio of the IC₅₀ value in the resistant divided by the IC₅₀ in the sensitive cell line; CEM/ADR5000, MDA-MB-231-BCRP, HCT116 (p53⁻/⁻), and U87MG.ΔEGFR were used as the corresponding resistant counterparts for CCRF-CEM, MDA-MB-231-pcDNA, HCT116 (p53^+/+), and U87MG, respectively; (): the selectivity index was determined as the ratio of the IC₅₀ value in the normal AML12 hepatocytes divided by the IC₅₀ in HepG2 hepatocarcinoma cells; in bold: significant cytotoxic effect [7, 39, 40], the cytotoxicity of compound 6 (betulenic acid) on these cell lines was previous reported [41], and this compound was no more tested in this study, no IC₅₀ value was recorded at up to 100 µM with compound 2; nd: not determined; 1: trichadonic acid; 3: 2-hydroxy-5-methoxyxanthone; 4: 1,3,6,7-tetrahydroxyxanthone or norathyriol; 5: 1,3,5,6-tetrahydroxyxanthone; 7: 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(6,8-dihydroxyxanthone)-1′,4′-dioxane; and 8: 3′-hydroxymethyl-2′-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5′,6′:5,6-(xanthone)-1′,4′-dioxane.