The Molecular Mechanisms Underlying the Antineoplastic Profile of Vitexin 2″-O-α-L-Rhamnopyranoside From Cordyline australis (G.Frost.): Isolation and Constituent Profiling

Cordyline australis (G.Forst.) Endl. Red Star leaves have been used in traditional medicine for several disorders. This study investigated the anticancer potential of C. australis leaves extract and characterized its bioactive constituents. Three compounds, a steroidal saponin, fruticoside K 23, and two flavonoids, vitexin 2″-O-α-l-rhamnopyranoside 35 and helichrysoside 68, were isolated and identified from its aqueous methanolic extract (CAME) using column chromatography. Seventy-nine additional compounds were tentatively identified using high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) analysis and The Global Natural Product Social Molecular Networking (GNPS-MN), with 57 compounds reported for the first time in the Cordyline genus. CAME and its isolated compounds were evaluated for cytotoxicity by MTT assay against seven different cancer cell lines. Vitexin 2″-O-α-l-rhamnopyranoside 35 exhibited significant cytotoxicity against HCT-116 colon cancer cells. Additionally, CAME, fruticoside K 23, and vitexin 2″-O-α-l-rhamnopyranoside 35 demonstrated significant cytotoxicity against osteosarcoma (HOS) cells. Afterwards, the safety profile of CAME and all the isolated compounds were examined upon human normal cells BJ-1. At 100 μg/mL, CAME and all isolated compounds showed a safe response on human normal BJ-1 cells (0.6%–8.5% cytotoxicity). Vitexin 2″-O-α-l-rhamnopyranoside 35 possessed the most significant selective anticancer response on osteosarcoma cells (HOS), with the least IC₅₀ value of 43.7 μg/mL. It induced apoptosis in HOS cells by modulating Bax, Bcl-2, and caspase-3 expression and caused G1 phase cell-cycle arrest. These results highlight C. australis as a source of potential anticancer agents, particularly vitexin 2″-O-α-l-rhamnopyranoside 35, which warrants further investigation for its therapeutic potential.