# Sulforaphane in Cancer Prevention and Therapy: A State-of-the-Art Review of Epidemiological Evidence, Molecular Mechanisms, and Translational Challenges

**Authors:** Jung Yoon Jang, Donghwan Kim, Na Kyeong Lee, Eunok Im, Nam Deuk Kim

PMC · DOI: 10.3390/ijms27042028 · International Journal of Molecular Sciences · 2026-02-20

## TL;DR

Sulforaphane, a compound in broccoli, shows promise in cancer prevention and treatment by affecting multiple biological pathways.

## Contribution

This paper provides a comprehensive review of sulforaphane's mechanisms, clinical potential, and translational challenges in cancer therapy.

## Key findings

- Sulforaphane activates Nrf2-ARE pathways and inhibits HDACs and HIF-1α to exert anticancer effects.
- Epidemiological evidence links cruciferous vegetable consumption to reduced cancer risk.
- Clinical trials show sulforaphane can reduce carcinogenic biomarkers and aid detoxification.

## Abstract

Sulforaphane (SFN), an aliphatic isothiocyanate derived from cruciferous vegetables such as broccoli, has emerged as a chemopreventive dietary agent. SFN exerts multifaceted anticancer effects through the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathways, inhibition of histone deacetylases (HDACs) and hypoxia-inducible factor-1α (HIF-1α), and regulation of apoptosis and autophagy. Epidemiological studies have consistently associated cruciferous vegetable intake with reduced cancer risk, while mechanistic research has elucidated the capacity of SFN to modulate redox balance, detoxification pathways, and epigenetic processes. Recent clinical trials have further demonstrated its potential to reduce carcinogenic biomarker levels and support metabolic detoxification. This review integrates evidence from epidemiological observations, molecular mechanisms, and clinical studies to provide a comprehensive understanding of the role of SFN in cancer prevention and therapy. Finally, translational challenges, including limited bioavailability, dose optimization, and standardization of broccoli-derived preparations, are discussed as critical factors for successfully translating SFN therapies from bench to bedside.

## Linked entities

- **Genes:** GABPA (GA binding protein transcription factor subunit alpha) [NCBI Gene 2551], are (Arylesterase) [NCBI Gene 59246804], HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091]
- **Chemicals:** Sulforaphane (PubChem CID 5350)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** Wnt3 (wingless-type MMTV integration site family, member 3) [NCBI Gene 22415] {aka Int-4, Wnt-3}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, Shh (sonic hedgehog) [NCBI Gene 20423] {aka 9530036O11Rik, Dsh, HHG-1, Hhg1, Hx, Hxl3}, GGT1 (gamma-glutamyltransferase 1) [NCBI Gene 2678] {aka CD224, D22S672, D22S732, GGT, GGT 1, GGTD}, HDAC1 (histone deacetylase 1) [NCBI Gene 3065] {aka GON-10, HD1, KDAC1, RPD3, RPD3L1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Cdk5 (cyclin dependent kinase 5) [NCBI Gene 12568] {aka Crk6}, REXO2 (RNA exonuclease 2) [NCBI Gene 25996] {aka CGI-114, REX2, RFN, SFN}, Cpt1a (carnitine palmitoyltransferase 1a, liver) [NCBI Gene 12894] {aka C730027G07, CPTI, Cpt1}, Prom1 (prominin 1) [NCBI Gene 19126] {aka 4932416E19Rik, AC133, CD133, Prom, Prom-1, Proml1}, Phc3 (polyhomeotic 3) [NCBI Gene 241915] {aka E030046K01Rik, Edr3, Hph3}, Myc (Myc proto-oncogene, bHLH transcription factor) [NCBI Gene 17869] {aka Myc2, Niard, Nird, bHLHe39}, Itga6 (integrin alpha 6) [NCBI Gene 16403] {aka 5033401O05Rik, Cd49f, VLA-6}, GSTK1 (glutathione S-transferase kappa 1) [NCBI Gene 373156] {aka GST, GST 13-13, GST13, GST13-13, GSTK1-1, hGSTK1}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, CKMT2 (creatine kinase, mitochondrial 2) [NCBI Gene 1160] {aka SMTCK}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, Cdk1 (cyclin dependent kinase 1) [NCBI Gene 12534] {aka Cdc2, Cdc2a, p34<CDC2>}, Aldh1a1 (aldehyde dehydrogenase family 1, subfamily A1) [NCBI Gene 11668] {aka ALDH-E1, ALHDII, Ahd-2, Ahd2, Aldh1, Aldh1a2}, ACACA (acetyl-CoA carboxylase alpha) [NCBI Gene 31] {aka ACAC, ACACAD, ACACalpha, ACC, ACC1, ACCA}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, Pou5f1 (POU domain, class 5, transcription factor 1) [NCBI Gene 18999] {aka NF-A3, Oct-3, Oct-3/4, Oct-4, Oct3, Oct3/4}, CASP9 (caspase 9) [NCBI Gene 842] {aka APAF-3, APAF3, ICE-LAP6, MCH6, PPP1R56}, Cdc25c (cell division cycle 25C) [NCBI Gene 12532] {aka Cdc25}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, JUNB (JunB proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 3726] {aka AP-1}, Tdgf1-ps2 (teratocarcinoma-derived growth factor, pseudogene 2) [NCBI Gene 21669] {aka Tdgf3}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, SREBF1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 6720] {aka HMD, IFAP2, SREBP1, bHLHd1}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Itgam (integrin alpha M) [NCBI Gene 16409] {aka CD11b/CD18, CR3, CR3A, Cd11b, F730045J24Rik, Ly-40}, PTGDR (prostaglandin D2 receptor) [NCBI Gene 5729] {aka AS1, ASRT1, DP, DP1, PTGDR1}, Slc7a11 (solute carrier family 7 (cationic amino acid transporter, y+ system), member 11) [NCBI Gene 26570] {aka 9930009M05Rik, sut, xCT}, SIRT3 (sirtuin 3) [NCBI Gene 23410] {aka SIR2L3}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, MAP2K7 (mitogen-activated protein kinase kinase 7) [NCBI Gene 5609] {aka JNKK2, MAPKK7, MEK, MEK 7, MKK7, PRKMK7}, CDC25C (cell division cycle 25C) [NCBI Gene 995] {aka CDC25, PPP1R60}, KLK3 (kallikrein related peptidase 3) [NCBI Gene 354] {aka APS, KLK2A1, PSA, hK3}, Srebf1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 20787] {aka ADD1, SREBP1, bHLHd1}, GPX4 (glutathione peroxidase 4) [NCBI Gene 2879] {aka GPx-4, GSHPx-4, MCSP, PHGPx, SMDS, snGPx}, Rexo2 (RNA exonuclease 2) [NCBI Gene 104444] {aka 1810038D15Rik, Rex2, Sfn, Smfn}, Fasn (fatty acid synthase) [NCBI Gene 14104] {aka A630082H08Rik, FAS}, PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, Cdk5r1 (cyclin dependent kinase 5, regulatory subunit 1) [NCBI Gene 12569] {aka Cdk5r, D11Bwg0379e, p25, p35}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, ULK1 (unc-51 like autophagy activating kinase 1) [NCBI Gene 8408] {aka ATG1, ATG1A, UNC51, Unc51.1, hATG1}, Cripto (cripto, EGF-CFC family member) [NCBI Gene 21667] {aka CR1, Tdgf1}, UGT1A (UDP glucuronosyltransferase family 1 member A complex locus) [NCBI Gene 7361] {aka GNT1, UGT, UGT1, UGT1A@}, HDAC9 (histone deacetylase 9) [NCBI Gene 9734] {aka HD7, HD7b, HD9, HDAC, HDAC7B, HDAC9B}, Raf1 (Raf1 proto-oncogene, serine/threonine kinase) [NCBI Gene 110157] {aka 6430402F14Rik, Craf1, D830050J10Rik, Raf-1, c-Raf, cRaf}, CCNB1 (cyclin B1) [NCBI Gene 891] {aka CCNB}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, Cttn (cortactin) [NCBI Gene 13043] {aka 1110020L01Rik, Ems1}, Cd24a (CD24a antigen) [NCBI Gene 12484] {aka Cd24, HSA, Ly-52, nectadrin}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Smo (smoothened, frizzled class receptor) [NCBI Gene 319757] {aka E130215L21Rik, Smoh, bnb, smoothened}
- **Diseases:** bronchial dysplasia (MESH:D001982), acute myeloid leukemia (MESH:D015470), lymph node carcinoma of the prostate (MESH:D011472), hypoxia (MESH:D000860), oral squamous cell carcinoma (MESH:D000077195), non-small cell lung cancer (MESH:D002289), triple-negative breast cancer (MESH:D064726), Breast Cancer (MESH:D001943), CSC (MESH:D018295), carcinogenesis (MESH:D063646), gastrointestinal malignancies (MESH:D005770), impaired liver or kidney function (MESH:D056486), gastrointestinal discomfort (MESH:D005767), Cancer (MESH:D009369), adenocarcinoma (MESH:D000230), RAF (MESH:D005354), lung cancer (MESH:D008175), esophageal squamous cell carcinoma (MESH:D000077277), cytotoxic (MESH:D064420), Prostate Cancer (MESH:D011471), metastasis (MESH:D009362), cardiovascular, metabolic, and neurodegenerative disorders (MESH:D019636), injury to (MESH:D014947), inflammation (MESH:D007249), headache (MESH:D006261), Colorectal Cancer (MESH:D015179), pancreatic cancer (MESH:D010190), carcinogenic (MESH:D011230), small cell lung cancer (MESH:D055752)
- **Chemicals:** glucosinolate (MESH:D005961), isothiocyanates (MESH:D017879), Mercapturic Acid (MESH:D000111), BITC (MESH:C031403), PEITC (MESH:C058305), ROS (MESH:D017382), cysteinyl-glycine (MESH:C028505), GSH (MESH:D005978), water (MESH:D014867), ATP (MESH:D000255), phospholipids (MESH:D010743), free fatty acids (MESH:D005230), iron (MESH:D007501), acetyl-CoA (MESH:D000105), CYS (MESH:D003545), lipid (MESH:D008055), NADPH (MESH:D009249), polysaccharide (MESH:D011134), thiol (MESH:D013438), fatty acid (MESH:D005227), SFN (MESH:C016766), Glucoraphanin (MESH:C119494), isothiocyanate (MESH:C037152), Zn2+ (-), metal (MESH:D008670), AITC (MESH:C004471)
- **Species:** gut metagenome (species) [taxon 749906], Brassica oleracea var. italica (asparagus broccoli, varietas) [taxon 36774], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), ZR-75-1 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0588), LNCaP — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0395), PANC-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480), HCT116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), 22Rv1 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_1045), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), SW480 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0546), TRAMP) C1 — Mus musculus (Mouse), Carcinoma of the mouse prostate gland, Cancer cell line (CVCL_B459)

## Full text

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## Figures

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## References

104 references — full list in the complete paper: https://tomesphere.com/paper/PMC12940376/full.md

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Source: https://tomesphere.com/paper/PMC12940376