Table 1.
Difference between gap junctional intercellular communication (GJIC) level in WB-F344 cells treated and non-treated with a chemopreventive agent (CPA) prior the addition of a GJIC inhibitor (Δ GJIC).
| ΔGJICa,b = M[GJIC(w/CPA)+(GJIC inhibitor)] − M[GJIC(w/o CPA)+(GJIC inhibitor)] |
||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chemopreventive agent | +GJIC inhibitor (15 min) | |||||||||||||
| Chemical | Concen- tration (µM) |
Pretreat -ment time |
ERK1/2-dependentc | ERK1/2 and PC-PLC- dependent |
ERK1/2 and PC-PLC- independent |
PC-PLC-dependent | ||||||||
| Lindane (70 µM) |
TPA (7.5 nM) |
PFOA (100 µM) |
Pentachlorophenol (70 µM) |
Fluoranthene (50 µM) |
DDT (25 µM) |
|||||||||
| Cinnamic acid | 100 | 30 min | 47 | (***P=0.001)d | 9 | (P=0.244) | 3 | (P=0.116) | 4 | (P=0.725) | 1 | (P=0.66) | −1 | (P=0.608) |
| Curcumin | 1 | 38 | (**P=0.004) | 1 | (P=0.525) | 34 | (**P=0.002) | 15 | (*P=0.05) | −1 | (P=0.367) | 0 | (P=0.788) | |
| Diallyl sulfide | 500 | 47 | (***P=0.001) | −3 | (P=0.169) | 6 | (P=0.19) | 4 | (P=0.34) | 5 | (P=0.159) | 0 | (P=0.606) | |
| Emodin | 10 | 27 | (***P=0.001) | 3 | (P=0.672) | −2 | (P=0.489) | −7 | (P=0.063) | −1 | (P=0.705) | 3 | (P=0.36) | |
| Indol-3-carbinol | 10 | 41 | (***P<0.001) | 10 | (P=0.194) | −1 | (P=0.584) | −3 | (P=0.58) | 0 | (P=1) | 2 | (P=0.909) | |
| Metformin | 1000 | 27 | (**P=0.004) | −2 | (P=0.672) | 6 | (P=0.328) | 14 | (*P=0.031) | 8 | (P=0.075) | 0 | (P=0.492) | |
| Quercetin | 100 | 69 | (***P<0.001) | 27 | (**P=0.008) | 43 | (***P<0.001) | 29 | (**P=0.008) | 19 | (**P=0.009) | 0 | (P=0.762) | |
| Silibinin | 100 | 78 | (***P=0.001) | 25 | (*P=0.011) | 58 | (***P=0.001) | 19 | (*P=0.05) | 26 | (**P=0.002) | 1 | (P=0.34) | |
| Thymoquinone | 10 | 48 | (***P<0.001) | 4 | (P=0.823) | 5 | (P=0.171) | 8 | (P=0.097) | 0 | (P=0.982) | 0 | (P=0.775) | |
| Cinnamic acid | 100 | 24 h | −6 | (P=0.351) | −1 | (P=0.525) | −3 | (P=0.133) | −7 | (P=0.119) | 1 | (P=0.279) | 11 | (*P=0.012) |
| Curcumin | 1 | 4 | (P=0.601) | 1 | (P=0.832) | 1 | (P=0.685) | −3 | (P=0.802) | 7 | (*P=0.013) | 0 | (P=0.689) | |
| Diallyl sulfide | 500 | 1 | (P=0.599) | 2 | (P=1) | −2 | (P=0.353) | −7 | (*P=0.031) | 7 | (*P=0.039) | 30 | (**P=0.005) | |
| Emodin | 10 | 3 | (P=0.501) | 2 | (P=0.112) | 6 | (P=0.121) | 4 | (P=0.88) | 17 | (**P=0.007) | 2 | (P=0.541) | |
| Indol-3-carbinol | 10 | −2 | (P=0.57) | −1 | (P=1) | 5 | (P=0.617) | 6 | (P=0.58) | 4 | (P=0.132) | 9 | (P=0.457) | |
| Metformin | 1000 | 2 | (P=0.699) | 6 | (P=0.138) | 0 | (P=0.867) | 5 | (P=0.898) | 9 | (P=0.066) | 26 | (**P=0.005) | |
| Quercetin | 25 | 42 | (***P=0.001) | 15 | (*P=0.015) | 3 | (P=0.263) | 39 | (**P=0.006) | 38 | (**P=0.002) | 5 | (*P=0.039) | |
| Silibinin | 50 | 26 | (*P=0.028) | 6 | (*P=0.044) | −2 | (P=0.584) | 13 | (**P=0.01) | 24 | (**P=0.002) | 1 | (P=0.391) | |
| Thymoquinone | 10 | −9 | (P=0.285) | −3 | (P=0.459) | 8 | (P=0.121) | 4 | (P=0.802) | 0 | (P=0.33) | 9 | (P=0.423) | |
TPA = 12-O-tetradecanoyl-phorbol-13-acetate, DDT = 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane, PFOA = perfluorooctanoic acid.
ΔGJIC was calculated as a difference between a median (M) value of GJIC (%control) obtained from experiments with a selected chemopreventive agent (CPA) and a given GJIC inhibitor, where the cells were pretreated for 30 min or 24 h with a selected CPA and then treated with GJIC inhibitor, i.e. (M[GJIC(w/ CPA)+(GJIC inhibitor)]), and a median value from experiments with a given GJIC inhibitor, where the cells were not pretreated with CPA, i.e. (M[GJIC(w/o CPA)+(GJIC inhibitor)]).
Shading indicates intensity of GJIC attenuation: 
none or weak effect (ΔGJIC ≤10%), 
mild effect (ΔGJIC >10 and ≤25%), 
moderate effect (ΔGJIC >25 and ≤50%), 
strong effect (ΔGJIC >50%)
Mechanism of GJIC inhibition
Significance of differences between GJIC in the cells treated and non-treated with a chemopreventive agent prior the addition of a GJIC inhibitor was determined by Mann-Whitney test, P values are given in parentheses and labelled with asterisks (*P≤0.05, **P≤0.01, ***P≤0.001)