Casticin in cancer research: in vitro evidence and mechanistic insights into its antitumor potential

Casticin (CAS), a natural flavonoid compound, has garnered increasing scientific interest due to its broad-spectrum anticancer properties. Originally recognized for its anti-inflammatory potential, CAS is now being extensively investigated for its ability to modulate key cellular processes involved in tumorigenesis. In vitro studies across a wide range of human cancer cell lines have consistently demonstrated that CAS inhibits cell viability, proliferation, and migration. Mechanistically, CAS exerts its antitumor effects through the modulation of multiple intracellular signaling pathways. Notably, CAS downregulates the PI3K/Akt/mTOR and MAPK/ERK pathways, both of which are critical regulators of cell growth and survival. It also activates the p53 tumor suppressor pathway and promotes mitochondrial apoptosis via the Bax/Bcl-2/caspase cascade. Furthermore, CAS has been shown to suppress the NF-κB signaling pathway, leading to reduced expression of pro-inflammatory and pro-survival genes, and to modulate the STAT3 signaling axis, contributing to the inhibition of tumor-promoting inflammation and metastasis. Through these pathways, CAS induces multiple forms of programmed cell death, including apoptosis, autophagy, ferroptosis, and pyroptosis. Additionally, CAS arrests the cell cycle at critical checkpoints-particularly at the G2/M phase-thereby disrupting uncontrolled cell division and enhancing cellular susceptibility to chemotherapeutic agents. This review provides a comprehensive overview of the current in vitro evidence supporting the anticancer potential of CAS, with a particular focus on its molecular mechanisms of action. The multifaceted nature of CAS activity highlights its promise as a potential adjunct or alternative in future cancer therapies.