# Natural compounds in ovarian cancer: mechanistic insights and therapeutic potential

**Authors:** Barathan Muttiah, Nur Atiqah Haizum Abdullah

PMC · DOI: 10.3389/fphar.2025.1687805 · 2026-01-22

## TL;DR

Natural compounds show promise in treating ovarian cancer by targeting multiple pathways and improving therapy outcomes, though challenges like poor bioavailability remain.

## Contribution

This review highlights the mechanistic insights and therapeutic potential of natural compounds in ovarian cancer, emphasizing their multi-targeted effects and translational challenges.

## Key findings

- Natural compounds inhibit cell proliferation and induce apoptosis in ovarian cancer cells.
- They modulate key signaling pathways like PI3K/AKT/mTOR and NF-κB, and influence epigenetic mechanisms.
- Despite strong preclinical evidence, clinical translation is limited by bioavailability and lack of specific trials.

## Abstract

Ovarian cancer is one of the most lethal gynecologic malignancies due to its late diagnosis, high recurrence rate, and chemoresistance. Recently, increasing evidence has emphasized the therapeutic potentials of natural compounds as multi-targeted agents in modulating key oncogenic pathways and improving standard therapies. This review critically examines the anticancer properties of various NCs, including quercetin, curcumin, resveratrol, EGCG, berberine, ellagic acid, withaferin A, celastrol, and others, against OC. These compounds display broad-spectrum activities: inhibition of cell proliferation, induction of apoptosis, modulation of oxidative stress, suppression of angiogenesis and metastasis, and reversal of chemoresistance. At the mechanistic level, NCs modulate several signaling pathways, such as PI3K/AKT/mTOR, NF-κB, MAPK, and Wnt/β-catenin pathways; and influence epigenetics and microRNA-mediated mechanisms. In contrast to compelling preclinical evidence, clinical translation remains limited due to poor bioavailability, the absence of OC-specific clinical trials, and regulatory constraints. The focus of future research should be on advanced drug delivery systems, omics-guided precision medicine, and sustainable sourcing strategies to overcome these translational barriers. The integration of NCs into combination and personalized regimens has promise for the improvement of therapeutic outcomes and overcoming chemoresistance in ovarian cancer.

## Linked entities

- **Chemicals:** quercetin (PubChem CID 5280343), curcumin (PubChem CID 969516), resveratrol (PubChem CID 5056), EGCG (PubChem CID 65064), berberine (PubChem CID 2353), ellagic acid (PubChem CID 5281855), withaferin A (PubChem CID 265237), celastrol (PubChem CID 122724)
- **Diseases:** ovarian cancer (MONDO:0005140)

## Full-text entities

- **Genes:** MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}
- **Diseases:** metastasis (MESH:D009362), Ovarian cancer (MESH:D010051), gynecologic malignancies (MESH:D005833)
- **Chemicals:** resveratrol (MESH:D000077185), EGCG (MESH:C045651), berberine (MESH:D001599), curcumin (MESH:D003474), quercetin (MESH:D011794), celastrol (MESH:C050414), OC (-), withaferin A (MESH:C009684), ellagic acid (MESH:D004610)

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12872805/full.md

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Source: https://tomesphere.com/paper/PMC12872805