# Evaluation of agmatine’s anti-cancer efficacy in Caco-2 colorectal adenocarcinoma cells

**Authors:** Esra Guzel Tanoglu, Muhammed Said Gokce, Miray Karamese, Sevde Altuntas, Ahsen Merve Bayrak, Alpaslan Tanoglu

PMC · DOI: 10.1007/s12032-026-03258-x · Medical Oncology (Northwood, London, England) · 2026-01-20

## TL;DR

This study shows that agmatine reduces the growth and spread of colon cancer cells and increases cell death, possibly through oxidative stress and apoptosis pathways.

## Contribution

The study demonstrates agmatine's anti-cancer effects in Caco-2 cells without affecting ABC transporter gene expression.

## Key findings

- Agmatine significantly reduced cell viability, migration, and invasion in Caco-2 cells.
- Agmatine increased apoptosis and decreased oxidative stress markers in treated cells.
- ABCG2, ABCB1, and ABCC1 gene expression levels were not significantly altered by agmatine treatment.

## Abstract

This study aimed to evaluate the potential effects of agmatine on cell viability, migration, invasion, apoptosis, and the expression of the ABCB1, ABCC1, and ABCG2 genes in the Caco-2 colon cancer cell line. Agmatine efficacy was assessed thruogh proliferation, migration, and invasion assays at various concentrations. The apoptotic index was determined using apoptosis-related markers (Bax, Bcl-2, Csp-3) via apoptosis assays, quantitative real-time PCR (qRT-PCR), and Western blot analysis. Expression levels of the ABCG2, ABCB1, and ABCC1 genes were measured by qRT-PCR in agmatine-treated Caco-2 cells. Oxidative stress markers, including glutathione peroxidase (GPx) and catalase (CAT), were evaluated by qRT-PCR. Cell viability analysis revealed that agmatine exerted its most pronounced effects at 72 h, with significant reductions at concentrations of 6, 7.3, and 9 mM in Caco-2 cells and 6, 6.25, and 9 mM in L929 cells (p < 0.05). At these concentrations, migration and invasion assays showed dose-dependent decreases in cell motility and invasiveness in Caco-2 cells. Apoptosis analysis demonstrated a significant increase in the apoptotic index with rising agmatine concentrations. Significant decreases in GPx and CAT were observed in all three agmatine-treated Caco-2 groups compared to untreated controls (p < 0.01). However, the expression levels of ABCG2, ABCB1, and ABCC1 showed no significant changes following agmatine treatment (p > 0.05). These findings indicate that agmatine exerts antiproliferative, anti-migratory, anti-invasive, and pro-apoptotic effects in Caco-2 colon cancer cells, potentially through the modulation of apoptosis- and oxidative stress–related pathways. The lack of significant impacts on ABC transporter gene expression suggests that agmatine may be a promising candidate molecule for further translational studies in colorectal cancer.

## Linked entities

- **Genes:** ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243], ABCC1 (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) [NCBI Gene 4363], ABCG2 (ATP binding cassette subfamily G member 2 (JR blood group)) [NCBI Gene 9429], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596], CSP3 (CS pseudogene 3) [NCBI Gene 440514], GPX (probable phospholipid hydroperoxide glutathione peroxidase) [NCBI Gene 103970350], CAT (catalase) [NCBI Gene 847]
- **Chemicals:** agmatine (PubChem CID 199)
- **Diseases:** colorectal cancer (MONDO:0005575)

## Full-text entities

- **Genes:** Rcan3 (regulator of calcineurin 3) [NCBI Gene 53902] {aka Csp3, Dscr1l2}, PGP (phosphoglycolate phosphatase) [NCBI Gene 283871] {aka AUM, G3PP, PGPase}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, ABCC2 (ATP binding cassette subfamily C member 2) [NCBI Gene 1244] {aka ABC30, CMOAT, DJS, MRP2, cMRP}, Bcl2 (B cell leukemia/lymphoma 2) [NCBI Gene 12043] {aka Bcl-2, C430015F12Rik, D630044D05Rik, D830018M01Rik}, ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, AZIN2 (antizyme inhibitor 2) [NCBI Gene 113451] {aka ADC, AZIB1, ODC-p, ODC1L, ODCp}, CAT (catalase) [NCBI Gene 847], POTEF (POTE ankyrin domain family member F) [NCBI Gene 728378] {aka A26C1B, POTE2alpha, POTEACTIN}, ABCB6 (ATP binding cassette subfamily B member 6 (LAN blood group)) [NCBI Gene 10058] {aka ABC, LAN, MTABC3, PRP, umat}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}, ABCG2 (ATP binding cassette subfamily G member 2 (JR blood group)) [NCBI Gene 9429] {aka ABC15, ABCP, BCRP, BMDP, CD338, CDw338}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, ABCC1 (ATP binding cassette subfamily C member 1 (ABCC1 blood group)) [NCBI Gene 4363] {aka ABC29, ABCC, DFNA77, GS-X, MRP, MRP1}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, Bax (BCL2-associated X protein) [NCBI Gene 12028], ODC1 (ornithine decarboxylase 1) [NCBI Gene 4953] {aka BABS, NEDBA, NEDBIA, ODC}
- **Diseases:** depression (MESH:D003866), diabetes mellitus (MESH:D003920), prostate cancer (MESH:D011471), anxiety disorders (MESH:D001008), prostate hepatocellular carcinoma (MESH:D011472), MDR (MESH:D018088), ischemic injury (MESH:D017202), CRC (MESH:D015179), inflammation (MESH:D007249), breast cancer (MESH:D001943), glioma (MESH:D005910), colon carcinoma (MESH:D003110), cancer (MESH:D009369), neuropathic pain (MESH:D009437)
- **Chemicals:** penicillin (MESH:D010406), Agmatine (MESH:D000376), Ninhydrin (MESH:D009555), paraformaldehyde (MESH:C003043), DMSO (MESH:D004121), EDTA (MESH:D004492), propidium iodide (MESH:D011419), streptomycin (MESH:D013307), cisplatin (MESH:D002945), PVDF (MESH:C024865), ATP (MESH:D000255), ROS (MESH:D017382), phospholipids (MESH:D010743), CO2 (MESH:D002245), MTT (MESH:C070243), PBS (MESH:D007854), crystal violet (MESH:D005840), 5-FU (MESH:D005472), LPS (MESH:D008070), Trizol (MESH:C411644), glutathione (MESH:D005978), TCA (MESH:D014238), Polyamine (MESH:D011073), SDS (MESH:D012967), OXA (MESH:D000077150), methanol (MESH:D000432), DAPI (MESH:C007293), PI (MESH:D010716), DMEM (-), TBS (MESH:D013725), doxorubicin (MESH:D004317)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), BV-2 — Mus musculus (Mouse), Transformed cell line (CVCL_0182), HCT-15 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0292), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), SK-MG-1 — Homo sapiens (Human), Astrocytoma, Cancer cell line (CVCL_1698), SW620 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0547), DLD-1 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0248), LoVo — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0399), L929 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_AR58), HCT-116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031)

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Source: https://tomesphere.com/paper/PMC12819543