# Targeting cancer hallmarks using resveratrol: isolation, formulation, and mechanisms of action

**Authors:** Wamidh H. Talib, Hadeel Shaher Al Junaidi, Rawan W. Hadi, Tassneem H. Ashour, Islam Z. Zabout, Suha M. Sabri, Heba K. Alshaeri, Douglas Law, Márta Hock, Viktória Prémusz

PMC · DOI: 10.3389/fnut.2026.1747820 · Frontiers in Nutrition · 2026-02-09

## TL;DR

Resveratrol, a natural compound, shows potential in fighting cancer by targeting multiple pathways involved in tumor growth and spread.

## Contribution

This review highlights resveratrol's mechanisms in targeting cancer hallmarks and its formulation for clinical use.

## Key findings

- Resveratrol reduces ROS and lipid peroxidation via the JNK/c-JUN pathway.
- It suppresses cancer cell proliferation by inhibiting the PI3K/Akt pathway and activating SIRT1.
- Resveratrol inhibits metastasis-related proteins like MMP-9, CXCR4, and FAK.

## Abstract

Natural products, particularly medicinal plants, play a crucial role in combating cancer and developing new treatments due to their unique properties, such as diverse chemical structures, low toxicity, and the ability to target various types of cancer. They offer a promising approach for the treatment and prevention of certain cancers. Resveratrol, a non-flavonoid polyphenolic compound found in several plants, has demonstrated beneficial effects on various diseases, including cancer, as evidenced by numerous studies. It may also help address multiple cancers by influencing their growth and metastasis. One proposed mechanism is that resveratrol reduces reactive oxygen species (ROS) and lipid peroxidation by activating the JNK/c-JUN signaling pathway, which enhances the expression of antioxidant enzymes. Additionally, resveratrol has been shown to regulate cell proliferation by suppressing the PI3K/Akt pathway and activating the SIRT1 pathway. Other mechanisms include the inhibition of NF-κB activation and the downregulation of downstream proteins such as MMP-9, CXCR4, and FAK, which are known to facilitate metastasis. Furthermore, resveratrol inhibits Akt phosphorylation, and inhibition of PI3K or mTOR mimics its effects on glucose uptake. This review discusses these mechanisms, emphasizing the anticancer properties of resveratrol and its role in various aspects of cancer, supported by research on the compound’s formulation and clinical studies involving this natural agent.

## Linked entities

- **Proteins:** MAPK8 (mitogen-activated protein kinase 8), JUN (Jun proto-oncogene, AP-1 transcription factor subunit), PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha), AKT1 (AKT serine/threonine kinase 1), SIRT1 (sirtuin 1), NFKB1 (nuclear factor kappa B subunit 1), MMP9 (matrix metallopeptidase 9), CXCR4 (C-X-C motif chemokine receptor 4), PTK2 (protein tyrosine kinase 2), MTOR (mechanistic target of rapamycin kinase)
- **Chemicals:** resveratrol (PubChem CID 5056)
- **Diseases:** cancer (MONDO:0004992)

## Full-text entities

- **Genes:** DEPTOR (DEP domain containing MTOR interacting protein) [NCBI Gene 64798] {aka DEP.6, DEPDC6, hDEPTOR}, APEX1 (apurinic/apyrimidinic endodeoxyribonuclease 1) [NCBI Gene 328] {aka APE, APE1, APEN, APEX, APX, HAP1}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, B3GAT2 (beta-1,3-glucuronyltransferase 2) [NCBI Gene 135152] {aka GLCATS}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, FAS (Fas cell surface death receptor) [NCBI Gene 355] {aka ALPS1A, APO-1, APT1, CD95, FAS1, FASTM}, TIGIT (T cell immunoreceptor with Ig and ITIM domains) [NCBI Gene 201633] {aka VSIG9, VSTM3, WUCAM}, THBS1 (thrombospondin 1) [NCBI Gene 7057] {aka THBS, THBS-1, TSP, TSP-1, TSP1}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, SNAI2 (snail family transcriptional repressor 2) [NCBI Gene 6591] {aka SLUG, SLUGH, SLUGH1, SNAIL2, WS2D}, ITGB1 (integrin subunit beta 1) [NCBI Gene 3688] {aka CD29, FNRB, GPIIA, MDF2, MSK12, VLA-BETA}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, RUNX3 (RUNX family transcription factor 3) [NCBI Gene 864] {aka AML2, CBFA3, PEBP2aC}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, CASP8 (caspase 8) [NCBI Gene 841] {aka ALPS2B, CAP4, Casp-8, FLICE, MACH, MCH5}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, PIK3R1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 5295] {aka AGM7, GRB1, IMD36, p85, p85-ALPHA, p85alpha}, KLRK1 (killer cell lectin like receptor K1) [NCBI Gene 22914] {aka CD314, D12S2489E, KLR, NKG2-D, NKG2D}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, CAMKK2 (calcium/calmodulin dependent protein kinase kinase 2) [NCBI Gene 10645] {aka CAMKK, CAMKKB}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, SP1 (Sp1 transcription factor) [NCBI Gene 6667], Tf (transferrin) [NCBI Gene 24825] {aka Tfn, Trf}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, CCND1 (cyclin D1) [NCBI Gene 595] {aka BCL1, D11S287E, PRAD1, U21B31}, HIF1A (hypoxia inducible factor 1 subunit alpha) [NCBI Gene 3091] {aka HIF-1-alpha, HIF-1A, HIF-1alpha, HIF1, HIF1-ALPHA, MOP1}, H2ax (H2A.X variant histone) [NCBI Gene 15270] {aka H2A.X, H2afx, Hist5-2ax, gammaH2ax}, Ogg1 (8-oxoguanine DNA glycosylase) [NCBI Gene 81528], IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CDK4 (cyclin dependent kinase 4) [NCBI Gene 1019] {aka CMM3, MCPH31, PSK-J3}, PDP1 (pyruvate dehydrogenase phosphatase catalytic subunit 1) [NCBI Gene 54704] {aka PDH, PDP, PDPC, PDPC 1, PPM2A, PPM2C}, NOS3 (nitric oxide synthase 3) [NCBI Gene 4846] {aka EC-NOS, ECNOS, MYMY8, NOSIII, cNOS, eNOS}, MCM4 (minichromosome maintenance complex component 4) [NCBI Gene 4173] {aka CDC21, CDC54, IMD54, NKCD, NKGCD, P1-CDC21}, NFKBIA (NFKB inhibitor alpha) [NCBI Gene 4792] {aka EDAID2, IKBA, MAD-3, NFKBI}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, PTK2B (protein tyrosine kinase 2 beta) [NCBI Gene 2185] {aka CADTK, CAKB, FADK2, FAK2, PKB, PTK}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, H3P16 (H3 histone pseudogene 16) [NCBI Gene 644914] {aka H3.6, H3F3AP6, p21}, NCR3 (natural cytotoxicity triggering receptor 3) [NCBI Gene 259197] {aka 1C7, CD337, LY117, MALS, NKp30}, IGFBP3 (insulin like growth factor binding protein 3) [NCBI Gene 3486] {aka BP-53, IBP-3, IBP3, IGFBP-3}, LGR5 (leucine rich repeat containing G protein-coupled receptor 5) [NCBI Gene 8549] {aka FEX, GPR49, GPR67, GRP49, HG38}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, FOXO3 (forkhead box O3) [NCBI Gene 2309] {aka AF6q21, FKHRL1, FKHRL1P2, FOXO2, FOXO3A}, RELA (RELA proto-oncogene, NF-kB subunit) [NCBI Gene 5970] {aka AIF3BL3, CMCU, NFKB3, p65}, SLC2A1 (solute carrier family 2 member 1) [NCBI Gene 6513] {aka CSE, DYT17, DYT18, DYT9, EIG12, GLUT}, MMRN1 (multimerin 1) [NCBI Gene 22915] {aka ECM, EMILIN4, GPIa*, MMRN}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, CXCR4 (C-X-C motif chemokine receptor 4) [NCBI Gene 7852] {aka CD184, D2S201E, FB22, HM89, HSY3RR, LCR1}, Apex1 (apurinic/apyrimidinic endodeoxyribonuclease 1) [NCBI Gene 79116] {aka APE, Apex, REF-1}, SNAI1 (snail family transcriptional repressor 1) [NCBI Gene 6615] {aka SLUGH2, SNA, SNAH, SNAIL, SNAIL1, dJ710H13.1}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}
- **Diseases:** gastrointestinal discomfort (MESH:D005767), ALL (MESH:D054198), cardiovascular diseases (MESH:D002318), cytotoxic (MESH:D064420), liver metastases (MESH:D009362), CRC (MESH:D015179), carcinogenic (MESH:D011230), death (MESH:D003643), intestinal damage (MESH:D007410), fungal infections (MESH:D009181), hepatocellular carcinoma (MESH:D006528), liver tumors (MESH:D008113), glioblastoma (MESH:D005909), renal toxicity (MESH:D007674), Retinoblastoma (MESH:D012175), breast cancer (MESH:D001943), HEN (MESH:D004751), Lewis lung carcinoma (MESH:D018827), Tumors (MESH:D009369), lung cancer (MESH:D008175), multiple myeloma (MESH:D009101), HNC (MESH:D006258), intestinal tumor (MESH:D007414), melanoma (MESH:D008545), trauma (MESH:D014947), Inflammation (MESH:D007249), mitochondrial damage (MESH:D028361), NSCLC (MESH:D002289), gastric cancer (MESH:D013274), nausea (MESH:D009325), obese (MESH:D009765), diarrhea (MESH:D003967), overweight (MESH:D050177), SBECD (MESH:D017086)
- **Chemicals:** Proanthocyanidins (MESH:D044945), Cyclodextrin (MESH:D003505), Ginkgolide (MESH:D046934), MTT (MESH:C070243), Polydatin (MESH:C058229), MDA (MESH:D008315), -FDG (MESH:D019788), Serine (MESH:D012694), curcumin (MESH:D003474), sodium bicarbonate (MESH:D017693), cisplatin (MESH:D002945), Lipo 2 (-), Magnesium dihydroxide (MESH:D008276), oxyresveratrol (MESH:C034912), carboplatin (MESH:D016190), TPGS (MESH:C014225), Sephadex LH-20 (MESH:C025614), poloxamer 188 (MESH:D020442), 1,2-Dimethylhydrazine (MESH:D019813), LiCl (MESH:D018021), resveratrol-3-O-glucuronide (MESH:C499731), glycosides (MESH:D006027), ROS (MESH:D017382), calcium (MESH:D002118), docetaxel (MESH:D000077143), glucose (MESH:D005947), chlorogenic acid (MESH:D002726), diethyl ether (MESH:D004986), flavonoid (MESH:D005419), carbon dioxide (MESH:D002245), citrate (MESH:D019343), polyphenol (MESH:D059808), ATP (MESH:D000255), SRB (MESH:C022027), LPS (MESH:D008070), lipid (MESH:D008055), paclitaxel (MESH:D017239), beta-cyclodextrin (MESH:C031215), dichloromethane (MESH:D008752), Z-VAD-FMK (MESH:C096713), lactate (MESH:D019344), pectin (MESH:D010368), PDTC (MESH:C066229), AG490 (MESH:C095512), fructose 2,6-bisphosphate (MESH:C027652), pentose phosphate (MESH:D010428), polymers (MESH:D011108), ADP (MESH:D000244), stilbene (MESH:D013267), dihydroresveratrol (MESH:C544754), methanol (MESH:D000432), platinum (MESH:D010984), pyruvate (MESH:D019289), glucuronide (MESH:D020719), alginate (MESH:D000464), sulfate (MESH:D013431), oxygen (MESH:D010100), Pyrrolidine Dithiocarbamate (MESH:C020972), copper (MESH:D003300), (E)-resveratrol (MESH:D000077185)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Avena sativa (cultivated oat, species) [taxon 4498], Homo sapiens (human, species) [taxon 9606], Polygonum cuspidatum (species) [taxon 83819], Solanum tuberosum (potatoes, species) [taxon 4113], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Mus musculus (house mouse, species) [taxon 10090], Reynoutria japonica (huzhang, species) [taxon 488216], Malus domestica (apple, species) [taxon 3750], Glycine max (soybean, species) [taxon 3847], Arachis hypogaea (goober, species) [taxon 3818], Veratrum grandiflorum (species) [taxon 203092], Juglans (walnuts, genus) [taxon 16718], Picea mariana (black spruce, species) [taxon 3335]
- **Cell lines:** H358 — Homo sapiens (Human), Minimally invasive lung adenocarcinoma, Cancer cell line (CVCL_1559), T47-D — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0553), MDA-MB-231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), SW480 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0546), SW620 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0547), HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), H4006 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_1269), HL-60 — Homo sapiens (Human), Adult acute myeloid leukemia with maturation, Cancer cell line (CVCL_0002), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), WiDr — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_2760), A549 lung adenocarcinoma — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_WN45), HeLa S3 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0058), A431 epidermoid carcinoma — Homo sapiens (Human), Cervical carcinoma, Cancer cell line (CVCL_JB76)

## Full text

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## Figures

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## References

142 references — full list in the complete paper: https://tomesphere.com/paper/PMC12926459/full.md

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Source: https://tomesphere.com/paper/PMC12926459