Usnic Acid induces dual-pathway apoptosis in SKOV-3 ovarian cancer cells via PARP1 inhibition and MAPK pathway activation
Human and Experimental Toxicology, cilt.44, 2025 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 44
- Basım Tarihi: 2025
- Doi Numarası: 10.1177/09603271251409541
- Dergi Adı: Human and Experimental Toxicology
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chimica, CINAHL, EMBASE, Environment Index, MEDLINE, Directory of Open Access Journals
- Anahtar Kelimeler: usnic acid, PARP1, MAPK signaling pathway, apoptosis, ovarian cancer
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Introduction: Due to its silent clinical progression and diagnosis often occurring at advanced stages, ovarian cancer continues to be a major contributor to gynecological cancer-related mortality worldwide. Recent evidence underscores the critical therapeutic value of targeting the interplay between DNA damage response pathways, particularly poly (ADP-ribose) polymerase 1 (PARP1), and mitogen-activated protein kinase (MAPK) signaling cascades. Methods: In this study, we investigated the anti-cancer potential of the naturally derived small molecule usnic acid in a chemotherapy-resistant epithelial ovarian cancer model (SKOV-3 cells) at the cellular and molecular levels. Results: Our findings demonstrate for the first time that usnic acid exerts a dual-pathway apoptotic mechanism by simultaneously inhibiting PARP1 and activating the MAPK signaling pathway. Remarkably, usnic acid mimics the gene-silencing action of siRNA on PARP1, suggesting a highly specific and potent inhibitory effect at the molecular level. Although ROS involvement and pathway causality were not directly tested, this dual-action profile enhances DNA damage-induced apoptosis and highlights usnic acid as a promising therapeutic candidate. Conclusion: The study presents a novel molecular framework in which a single small molecule can coordinate apoptosis through parallel regulatory pathways, demonstrating the potential for innovative therapeutic approaches in the treatment of aggressive and treatment-resistant ovarian cancers.