# Network pharmacology approach identifies novel anticancer botanicals: Experimental exploration of Falcaria vulgaris (Sickleweed) as a therapeutic candidate

**Authors:** Zahra Samadi, Eisa Kohan-Baghkheirati, Madjid Momeni-Moghaddam, Toktam Hajjar, Zahra Ghavidel, Awatif Al-Judaibi, Awatif Al-Judaibi, Awatif Al-Judaibi, Awatif Al-Judaibi

PMC · DOI: 10.1371/journal.pone.0334417 · PLOS One · 2026-02-27

## TL;DR

This paper introduces a network pharmacology method to find anticancer plants, validating Falcaria vulgaris as a promising new candidate through experiments.

## Contribution

A novel network pharmacology approach is introduced and experimentally validated for identifying anticancer botanicals.

## Key findings

- Falcaria vulgaris extract showed high peroxidase activity, flavonoid content, and total phenolics.
- GC-MS identified 22 bioactive compounds with antioxidant, anticancer, and anti-inflammatory properties.
- The extract caused significant cell death in breast cancer cell lines MCF-7 and 4T1.

## Abstract

Cancer remains a major global health challenge with limited therapeutic options. Medicinal plants have emerged as promising candidates for anticancer drug discovery. This study introduces an innovative network pharmacology approach to predict potential anticancer botanicals by analyzing their metabolite profiles. Through bipartite network analysis of 3,250 plants and 667 experimentally validated anticancer metabolites, we identified 61 top-ranked plants, among which 85.25% exhibited known anticancer properties, while 14.75% represented novel candidates. Further experimental validation of F. vulgaris extract revealed its predicted anticancer potential. Biochemical analyses demonstrated high peroxidase activity (0.063 AU/min per mg protein), substantial flavonoid content (178.33 ± 18.3 mg QE/g), and elevated total phenolics (643.3 ± 20.8 mg GAE/g). GC-MS analysis identified 22 bioactive compounds, predominantly featuring documented antioxidant, anticancer, and anti-inflammatory properties. The extract exhibited significant dose-dependent cytotoxicity against breast cancer cell lines, with MTT assays showing significant inhibition (p < 0.0001) in both MCF-7 and 4T1 cells. Flow cytometry analysis further confirmed remarkable cell death induction, with rates reaching 90.51% (MCF-7) and 97.4% (4T1) at 10 mg/mL concentration of the extract. These experimental results robustly validate our network pharmacology approach for efficiently identifying anticancer botanicals through their metabolite profiles. This integrative strategy connects computational prediction with experimental validation, providing a scalable framework for discovering plant-derived therapeutics. Our findings not only explore F. vulgaris as a promising candidate but also cover the way for systematic exploration of understudied botanicals in oncology.

## Linked entities

- **Chemicals:** flavonoid (PubChem CID 10251), QE (PubChem CID 7020029), GAE (PubChem CID 3037582)
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** ALDH1A1 (aldehyde dehydrogenase 1 family member A1) [NCBI Gene 216] {aka ALDC, ALDH-E1, ALDH1, ALDH11, HEL-9, HEL-S-53e}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, BCL2L1 (BCL2 like 1) [NCBI Gene 598] {aka BCL-XL/S, BCL2L, BCLX, Bcl-X, PPP1R52}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, NANOG (Nanog homeobox) [NCBI Gene 79923], 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}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PROM1 (prominin 1) [NCBI Gene 8842] {aka AC133, CD133, CORD12, MCDR2, MSTP061, PROML1}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, POU5F1 (POU class 5 homeobox 1) [NCBI Gene 5460] {aka OCT3, OCT4, OCT4Borf1, OTF-3, OTF3, OTF4}, COL11A2 (collagen type XI alpha 2 chain) [NCBI Gene 1302] {aka DFNA13, DFNB53, FBCG2, HKE5, OSMEDA, OSMEDB}, TXK (TXK tyrosine kinase) [NCBI Gene 7294] {aka BTKL, PSCTK5, PTK4, RLK, TKL}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}
- **Diseases:** Falcaria vulgaris (MESH:D016112), metastasis (MESH:D009362), hormone receptor (MESH:D046150), hematological toxicity (MESH:D006402), gastrointestinal disorders (MESH:D005767), cytotoxic (MESH:D064420), F. vulgaris (OMIM:102510), weight loss (MESH:D015431), Breast Cancer (MESH:D001943), TNBC (MESH:D064726), necrosis (MESH:D009336), prostate cancer (MESH:D011471), inflammatory (MESH:D007249), liposarcoma (MESH:D008080), diabetic (MESH:D003920), Cancer (MESH:D009369), lung carcinoma (MESH:D008175), gastric adenocarcinoma (MESH:D013274), nausea (MESH:D009325), bleeding (MESH:D006470), fatigue (MESH:D005221)
- **Chemicals:** Palmitate (MESH:D010168), Carvacrol (MESH:C073316), helium (MESH:D006371), 3-O-Caffeoylquinic acid (-), hydrogen peroxide (MESH:D006861), penicillin (MESH:D010406), Eicosane (MESH:C050821), MTT (MESH:C070243), guaiacol (MESH:D006139), caryophyllene oxide (MESH:C515179), vinca alkaloids (MESH:D014748), Fatty acids (MESH:D005227), hydrocarbons (MESH:D006838), Octadecadienoic acid (MESH:C027369), phenols (MESH:D010636), tannin (MESH:D013634), erlotinib (MESH:D000069347), CO2 (MESH:D002245), Steroids (MESH:D013256), aluminum chloride (MESH:D000077410), Naringenin (MESH:C005273), sodium carbonate (MESH:C005686), p-Coumaric Acid (MESH:C495469), palmitic acid (MESH:D019308), lipids (MESH:D008055), Caffeic Acid (MESH:C040048), anthocyanins (MESH:D000872), coumarins (MESH:D003374), luteolin (MESH:D047311), oleic acid (MESH:D019301), saponins (MESH:D012503), Flavonoids (MESH:D005419), Stigmasterol (MESH:D013265), anthraquinones (MESH:D000880), methanol (MESH:D000432), Linoleate (MESH:D019787), Gallic acid (MESH:D005707), Phytol (MESH:D010836), Spathulenol (MESH:C013258), PI (MESH:D010716), Hexadecenoic acid (MESH:C093821), phosphate (MESH:D010710), hesperidin (MESH:D006569), quercetin (MESH:D011794), phytosterol (MESH:D010840), Loliolide (MESH:C030425), streptomycin (MESH:D013307), Rutin (MESH:D012431), Tetraguaiacol (MESH:C430963), sodium nitrite (MESH:D012977), DPPH (MESH:C004931), alpha-pinene (MESH:C005451), cerium oxide (MESH:C030583), water (MESH:D014867), phenol (MESH:D019800), Hyperin (MESH:C021304), catechins (MESH:D002392), essential oils (MESH:D009822), Terpenes (MESH:D013729), BHT (MESH:D002084)
- **Species:** Psidium guajava (guava, species) [taxon 120290], Angelica furcijuga (species) [taxon 358456], Rattus norvegicus (brown rat, species) [taxon 10116], Viscum album (European mistletoe, species) [taxon 3972], Homo sapiens (human, species) [taxon 9606], Trifolium pratense (peavine clover, species) [taxon 57577], Diospyros kaki (Japanese persimmon, species) [taxon 35925], Calligonum leucocladum (species) [taxon 1202986], Punica granatum (granado, species) [taxon 22663], Juniperus thurifera (species) [taxon 177241], Halymenia durvillei (species) [taxon 313575], Salvia officinalis (garden sage, species) [taxon 38868], Mus musculus (house mouse, species) [taxon 10090], Urtica dioica (great nettle, species) [taxon 3501], Zanthoxylum dipetalum (species) [taxon 1336649], Ophiorrhiza liukiuensis (species) [taxon 489897], Phedimus takesimensis (species) [taxon 904691], Falcaria vulgaris (species) [taxon 52469]
- **Cell lines:** 4T1 — Mus musculus (Mouse), Malignant neoplasms of the mouse mammary gland, Cancer cell line (CVCL_0125), ATCC CRL-2539 — Homo sapiens (Human), Turner syndrome, Transformed cell line (CVCL_9K25), PC3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035), 3T3 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), SW-872 — Homo sapiens (Human), Liposarcoma, Cancer cell line (CVCL_1730), RINm5F — Rattus norvegicus (Rat), Rat insulinoma, Cancer cell line (CVCL_0501), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), HTB-22 — Mus musculus (Mouse), Hybridoma (CVCL_A8FQ), SiHa — Homo sapiens (Human), Human papillomavirus-related cervical squamous cell carcinoma, Cancer cell line (CVCL_0032), NCCIT — Homo sapiens (Human), Testicular embryonal carcinoma, Cancer cell line (CVCL_1451), ATCC CRL-1658 — Homo sapiens (Human), Nevoid basal cell carcinoma syndrome, Finite cell line (CVCL_2Z69), MCF-7/4T1 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_JX64), AGS — Homo sapiens (Human), Gastric adenocarcinoma, Cancer cell line (CVCL_0139), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031)

## Full text

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## Figures

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## References

90 references — full list in the complete paper: https://tomesphere.com/paper/PMC12948079/full.md

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Source: https://tomesphere.com/paper/PMC12948079