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. Author manuscript; available in PMC: 2016 May 1.
Published in final edited form as: Curr Pharmacol Rep. 2015 Jan 30;1(3):179–196. doi: 10.1007/s40495-015-0017-y

Table 1. Examples of the effect of dietary glucosinolate derivatives on DNA methylation, histone modifications and miRNAs mechanisms.

Epigenetic mechanism Dietary agent Molecular mechanism Validated target(s) In vitro model In vivo model Concentration Treatment duration References
DNA methylation Sulforaphane ↓methylation in promoter region, ↓ DNMT1, ↓ DNMT3a Nrf2 TRAMPC1 mouse prostate cells 2.5 μM 5 days [40]
Sulforaphane ↓methylation in promoter region, ↓ DNMT1, ↓ DNMT3a, ↓ DNMT3b Nrf2 JB6 P+ mouse skin cancer cells 2.5 μM 5 days [45]
Sulforaphane ↓ DNMT1 expression Caco-2 human colon cancer cells 50 μM 5 days [80]
Sulforaphane ↓methylation in promoter region, ↓ DNMT1 and ↓DNMT3a hTERT MCF-7 and MDA-MB-231 human breast cancer cells 10 μM 6 days [23, 81]
Phenethyl isothiocyanate ↓methylation in promoter region GSTP1 LNCap (androgen-dependent/independe nt) human prostate cancer cells 2.0 μM 5 days [82]
3.3′-diindolylmethane ↓methylation in promoter region, ↓ DNMT1, ↓ DNMT3a, ↓ DNMT3b Nrf2 TRAMPC1 mouse prostate cells TRAMP mice prostate tumors 5 μM / 1% DIM diet 5 days / 24 weeks [83]
3.3′-diindolylmethane (formulation with higher bioavailability) miR-34a LNCaP and C4-2B human prostate cancer cells 6 μM 5 days [100]
3.3′-diindolylmethane ↓methylation in promoter region, ↓ DNMT1, ↓ DNMT3b TGFBR1, CYR61 LNCap human prostate cancer cells 15 μM 48 hours [11]
Histone modifications Sulforaphane ↓HDAC1, ↓HDAC4, ↓HDAC5, ↓HDAC7, ↑H3Ac Nrf2 Mouse prostate TRAMPC1 cells 2.5 μM 5 days [40]
Sulforaphane ↓HDAC1, ↓HDAC2, ↓HDAC3, ↓HDAC4 Nrf2 Mouse skin JB6 P+ cells 2.5 μM 5 days [45]
Sulforaphane ↓ HDAC activity, ↑ H3Ac, ↑H4Ac p21, bax Apcmin mice colon tumors Single oral dose of 10 μM / ∼6 μM 6 hours / 10 weeks [87]
Sulforaphane ↓ HDAC activity, ↑ H3Ac, ↑H4Ac p21 Human colorectal HCT116 cells 15 μM 47 hours [119]
Sulforaphane ↓ HDAC activity, ↑ H3Ac, ↑H4Ac p21, bax Human prostate BPH-1, LnCaP and PC-3 cells 15 μM 48 hours [120]
Sulforaphane ↓ HDAC activity, ↓HDAC1 Human embryonic kidney 293 cells 15 μM 47 hours [119]
Sulforaphane ↓ HDAC activity, ↑ global histone acetylation Human PC-3 prostate cancer xenografts in nude mice 7.5 μmol per animal 21 days [90]
Sulforaphane ↓ HDAC activity, ↑H3Ac, ↑H4Ac Human peripheral blood mononuclear cells (PBMC) 68 g BroccoSprouts 3 and 6 hours following consumption [90]
Sulforaphane ↓ HDAC activity Human breast MDA-MB-231, MDA-MB-468, MCF-7, and T47D cell lines 25 μM 48 hours [121]
Sulforaphane ↓ HDAC activity, ↑H3Ac, ↑H4Ac, ↑H3K9Ac, ↓H3K9, ↓H3K27, ↑RBP2 hTERT MCF-7 and MDA-MB-231 human breast cancer cells 10 μM 6 days [23, 81]
Sulforaphane ↓H3K27 Human SCC-13 skin cancer cells 20 μM 48 hours [91]
Phenethyl isothiocyanate ↓HDAC expression, ↑H3Ac, ↑H3K4, ↓H3K9, ↓ HDAC1 Human prostate LNCap cells 0.1-20 μM 36 hours [82]
Phenethyl isothiocyanate ↑H3Ac, ↑H3K4, ↓H3K9 p21 Human prostate LNCap cells 10 μM 30 hours [88]
Phenylhexyl isothiocyanate ↓HDAC activity, ↑H3Ac, ↑H4Ac, ↑H3K14, ↑H3K4, ↓H3K9 p21 Human leukemia HL-60 cells 40 μM 7 hours [122]
3.3′-diindolylmethane ↓HDAC1, ↓HDAC2, ↓HDAC3, ↓HDAC4 Human colon HT-29 cells 60 μM 24 hours [123]
3.3′-diindolylmethane ↓HDAC1, ↓HDAC2, ↓HDAC3, ↓HDAC4 p21, p27 Human colon HT-29 and SW620 cells Human HT-29 colon cancer xenografts in nude mice 60 μM / 300 mg/kg/day 24 hours / 2 days [93]
3.3′-diindolylmethane ↑ histone acetyl transferase p300, ↑H4Ac COX-2 Human breast MCF-7 cells 10 μM 15 minutes [89]
3.3′-diindolylmethane ↓HDAC1, ↓HDAC2, ↓HDAC3, ↓HDAC4, ↓HDAC8 Mouse prostate TRAMPC1 cells 5 μM 5 days [83]
3.3′-diindolylmethane ↑H3K4 TGFBR1, CYR61 LNCap human prostate cancer cells 15 μM 48 hours [11]
microRNAs Sulforaphane miR-140, miR-29a, and miR-21 MCF10DCIS, MCF-7, MDA-MB-231 breast cancer cells 10 μM 7 days [103]
Sulforaphane miR-let7-a K-ras BxPc-3, MIA-PaCa2 pancreatic cancer cells 10 μM 72 hours [102]
3.3′-diindolylmethane miR-200b, miR-200c, let-7b, let-7c, let-7d, and let-7e ZEB1 MiaPaCa-2, Panc-1, and Aspc-1 pancreatic cancer cells 25 μM 48 hours [97]
3.3′-diindolylmethane miR-146a EGFR, IRAK-1, and MTA-2 Colo357 and Panc-1 pancreatic cancer cells 25 μM 48 hours [124]
3.3′-diindolylmethane miR-21 Cdc25A MCF-7 and MDA-MB-468 breast cancer cells Human MCF-7 breast cancer xenografts in nude mice 30-60 μM / 5 mg/kg 24-96 hours / 7 weeks after cell injection [99]
3.3′-diindolylmethane (formulation with higher bioavailability) let-7a, let-7b, let-7c, and let-7d EZH2 LNCaP, C4-2B and PC3 human prostate cancer cells Human prostate samples from patients with stage I or stage II Pca undergoingradical prostatectomy 25 μM / 225 mg orally twice daily x 14-72 days (based on scheduling of surgery) 24 hours / 2–4 weeks prior to surgery [101]
Indole-3-carbinol miR-21, miR-31, miR-130a, and miR-146 Human lung carcinoma A549 cells Vinyl carbamate-induced female A/J mice lung tumors 100 - 150 μM 24 hours / 15 weeks [98]
Indole-3-carbinol miR-10a, miR-26a, miR-34b, miR-125a-prec Sprague-Dawley rats lung cancer samples induced by environmen tal cigarette smoke (ECS) 2,500 mg/kg diet 28 days [12]
Phenethyl isothiocyanate let-7a, let-7c, miR-26b, miR-99b, miR-123-prec, miR-125b, miR-146-prec, miR-192, miR-222-prec Sprague-Dawley rats lung cancer samples induced by environmen tal cigarette smoke (ECS) 500 mg/kg diet 28 days [12]