Natural compounds in ovarian cancer: mechanistic insights and therapeutic potential

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.