Epigenetic synergy between decitabine and platinum derivatives

Clinical Epigenetics

Table 1 A list of anti-cancer drugs used for screening of GFP reactivation

Drugs (dose range tested)	Category	Conc. producing the highest GFP	GFP % ± SEM drug alone	GFP ratio (±SEM)^a
Carmustine (50–100 nM)	Alkylating agent	50 nM	0.1 ± 0.1	0.86 ± 0.15
Mechlorethamine (50–100 nM)	Alkylating agent	100 nM	0.2 ± 0.2	1.82 ± 0.1^c
Carboplatin (50–75 μM)	Alkylating agent	75 μM	0.4 ± 0.1	1.86 ± 0.83^c
Oxaliplatin (5–20 μM)	Alkylating agent	20 μM	2.2 ± 2.0	1.58 ± 1.1
Cisplatin (200–500 nM)	Alkylating agent	500 nM	0.1 ± 0.1	1.07 ± 0.14
Chlorambucil (10–50 μM)	Alkylating agent	50 μM	0.3	1.1
Temozolomide (50–75 μM)	Alkylating agent	75 μM	0.2	1.28^b
Fludarabine (10 μM)	Antimetabolite	10 μM	0.1 ± 0.1	0.99 ± 0.45
Cytarabine	Antimetabolite	10 nM	0.1	1.21 ± 0.24
Gemcitabine (100–400 nM)	Antimetabolite	200 nM	0.9	0.86
Fluorouracil (100–400 nM)	Antimetabolite	200 nM	0.2 ± 0.1	0.48 ± 0.28
Clofarabine (100–500 nM)	Antimetabolite	100 nM	0.1	0.04
Irinotecan (25–100 nM)	Topoisomerase I inhibitor	25 nM	0.2 ± 0.1	1.47 ± 0.12^c
Etoposide	Topoisomerase I inhibitor	100 nM	0.2	0.87 ± 0.07
Paclitaxel (1–10 nM)	Antimicrotubule agent	10 nM	2.2 ± 0.8	0.92 ± 0.04
Mitomycin C	Antitumor antibiotic	100 μg/mL	1.1 ± 0.8	1.1 ± 0.1
Doxorubicin	Anthracycline antibiotic		ND (autofluorescent)
Idarubicin	Anthracycline antibiotic		ND (autofluorescent)

In these experiments, anti-cancer drug treatment (for 24 h) was performed following decitabine pre-treatment at 100 nM for 72 h. GFP ratio was calculated for each experiment by dividing the GFP signal obtained for the drug combination by the signal produced by decitabine alone for each experiment
^aData shown were selected for doses producing the highest GFP percentage (±SEM)
^bHigher concentrations of temozolomide of 200 and 250 μM in combination with decitabine produced respectively 30 and 41.4 % of GFP positive cells
^cA significant increase in GFP ratio

ISSN: 1868-7083