# Swertiamarin fails to induce cytotoxicity in colon cancer cell lines: Evidence against a direct anticancer effect

**Authors:** Ghada Khawaja, Aya Shoujaa, Youmna El-Orfali, Sonia Abou Najem, Michel J. Massaad

PMC · DOI: 10.1371/journal.pone.0344653 · PLOS One · 2026-03-16

## TL;DR

Swertiamarin does not kill colon cancer cells but shows strong antioxidant and antimicrobial properties, suggesting it may help prevent cancer rather than treat it.

## Contribution

This study provides evidence against the direct anticancer effect of Swertiamarin in colon cancer models.

## Key findings

- Swertiamarin had minimal or no effect on CRC cell proliferation, migration, or morphology.
- Swertiamarin showed strong antioxidant activity and antimicrobial effects against E. coli and S. aureus.
- Swertiamarin did not enhance the cytotoxicity of 5-fluorouracil in CRC cells.

## Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide, with rising incidence linked to unhealthy lifestyle habits. Although 5-fluorouracil (5-FU) remains a standard therapy, its efficacy is often limited by resistance and adverse effects. These limitations have driven interest in plant-derived bioactive compounds as complementary or alternative therapies. This study investigated the potential anticancer effects of Swertiamarin (SWT), a seco-iridoid glycoside with reported anti-inflammatory and antioxidant properties.

Three human CRC cell lines (HT-29, HCT-116, and Caco-2) and a non-cancerous (Vero E6) cell line were treated with SWT sourced from three independent suppliers to ensure reproducibility. Cell viability was evaluated using Trypan blue exclusion and MTT assays, while scratch assay and microscopic analyses were used to assess migration and morphological changes. The antioxidant capacity of SWT was measured using hydrogen peroxide scavenging assays, and its antimicrobial activity was tested against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus).

SWT exhibited minimal or no effect on cell proliferation across all cell lines, concentrations, and time points, while 5-FU significantly reduced cell viability. Co-treatment with SWT and 5-FU did not enhance cytotoxicity, indicating no synergistic effect. SWT also had no impact on cell migration or morphology. However, it demonstrated strong antioxidant activity comparable to ascorbic acid and displayed antimicrobial effects, transiently inhibiting E. coli and persistently suppressing S. aureus.

SWT does not exert direct cytotoxic or antimigratory effects in CRC models but possesses potent antioxidant and antimicrobial activities. These findings suggest a possible chemopreventive or protective role for SWT rather than a therapeutic one. This study underscores the importance of rigorous and reproducible evaluation of pure natural products to accurately define their biological and therapeutic potential.

## Linked entities

- **Chemicals:** 5-fluorouracil (PubChem CID 3385), Swertiamarin (PubChem CID 442435), hydrogen peroxide (PubChem CID 784), ascorbic acid (PubChem CID 9888239)
- **Diseases:** colorectal cancer (MONDO:0005575)
- **Species:** Escherichia coli (taxon 562), Staphylococcus aureus (taxon 1280)

## Full-text entities

- **Genes:** AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, GSTK1 (glutathione S-transferase kappa 1) [NCBI Gene 373156] {aka GST, GST 13-13, GST13, GST13-13, GSTK1-1, hGSTK1}, SOD1 (superoxide dismutase 1) [NCBI Gene 6647] {aka ALS, ALS1, HEL-S-44, IPOA, SOD, STAHP}, GSR (glutathione-disulfide reductase) [NCBI Gene 2936] {aka CNSHA10, GR, GSRD, HEL-75, HEL-S-122m}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CAT (catalase) [NCBI Gene 847], CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}
- **Diseases:** adenocarcinoma (MESH:D000230), deaths (MESH:D003643), cervical cancer (MESH:D002583), liver and gastric cancer (MESH:D013274), hepatocellular carcinoma (MESH:D006528), Cytotoxicity (MESH:D064420), CRC (MESH:D015179), cancer (MESH:D009369), Crohn's disease (MESH:D003424), colitis (MESH:D003092), colorectal adenocarcinoma (MESH:D003110), inflammatory (MESH:D007249)
- **Chemicals:** 267-1068microM (-), streptomycin (MESH:D013307), Amikacin (MESH:D000583), SWT (MESH:C013270), L-glutamine (MESH:D005973), formazan (MESH:D005562), 5-FU (MESH:D005472), ROS (MESH:D017382), thymoquinone (MESH:C003466), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MESH:C022616), Saponin (MESH:D012503), PBS (MESH:D007854), seco-iridoid glycoside (MESH:D057889), DMSO (MESH:D004121), penicillin (MESH:D010406), H2O2 (MESH:D006861), CO2 (MESH:D002245), Ascorbic Acid (MESH:D001205), Trypan blue (MESH:D014343), isopropanol (MESH:D019840), MTT (MESH:C070243)
- **Species:** Staphylococcus aureus (species) [taxon 1280], Rodentia (rodent, order) [taxon 9989], Homo sapiens (human, species) [taxon 9606], Pseudomonas aeruginosa (species) [taxon 287], Bacillus subtilis (species) [taxon 1423], Escherichia coli (E. coli, species) [taxon 562]
- **Cell lines:** African green monkey — Chlorocebus aethiops (Green monkey), Embryonic stem cell (CVCL_RY74), ATCC-CCL-247 — Mus musculus (Mouse), Undefined cell line type (CVCL_M023), Vero E6 — Chlorocebus sabaeus (Green monkey), Spontaneously immortalized cell line (CVCL_0574), ATCC- HTB-37 — Mus musculus (Mouse), Hybridoma (CVCL_A8FQ), T8154 — Homo sapiens (Human), Esophageal squamous cell carcinoma, Cancer cell line (CVCL_3174), HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), ATCC- C1008 — Homo sapiens (Human), Transformed cell line (CVCL_K755), SWT-alpha — Mus musculus (Mouse), Transformed cell line (CVCL_AW09), HCT-116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), SWT-beta — Gorilla gorilla gorilla (Western lowland gorilla), Transformed cell line (CVCL_R799), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), ATCC- HB-8065 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), SWT-gamma — Homo sapiens (Human), Fibrosarcoma, Cancer cell line (CVCL_C0D3), CRC — Homo sapiens (Human), Colorectal carcinoma, Cancer cell line (CVCL_A1EX), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027)

## Full text

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## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12991280/full.md

## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12991280/full.md

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Source: https://tomesphere.com/paper/PMC12991280