Conferone: Sources, Anticancer Mechanisms, and Potential in Overcoming Chemoresistance - A Comprehensive Review

Cancer remains a leading cause of mortality worldwide, and limitations of conventional therapies such as toxicity and Multidrug Resistance (MDR) highlight the need for safer and more effective agents. Natural compounds derived from medicinal plants have gained attention as potential anticancer therapeutics. Conferone, a sesquiterpene coumarin isolated mainly from Ferula species, has shown promising biological activities.

This review comprehensively summarizes available primarily in vitro studies, with very limited in vivo evidence investigating the anticancer properties of conferone. Data were collected from published experimental studies focusing on its chemical characteristics, pharmacological effects, molecular mechanisms, and efficacy across different cancer cell lines.

Conferone exhibits significant anticancer activity against a wide range of malignancies, including leukemia/lymphoma, breast, colorectal, bladder, ovarian, and embryonal cancers. Its mechanisms involve induction of mitochondrial-dependent apoptosis, cell cycle arrest, increased oxidative stress, inhibition of angiogenesis, and modulation of oncogenic signaling pathways such as NF-κB, c-MYC, and CDK6. Notably, conferone exhibits MDR-modulating activity by inhibiting ATP-binding cassette transporters (e.g., P-gp and MRP2), thereby enhancing intracellular accumulation and efficacy of chemotherapeutic agents like doxorubicin, vincristine, and cisplatin. Incorporation into nanocarrier-based delivery systems further improves its bioavailability and anticancer potency.

Conferone is a multifunctional natural compound with strong anticancer and chemosensitizing properties. Although current findings are encouraging, further in vivo and clinical investigations are required to clarify its pharmacokinetics, safety profile, and therapeutic potential in cancer treatment.