Bioactivity-Guided Isolation of Cytotoxic Compounds From Curcuma caesia: In Vitro and In Silico Investigation for Oral Cancer.

Oral cancer remains a major public health concern, especially in Southeast Asia. Conventional treatments such as chemotherapy and immunotherapy are limited by severe side effects and drug resistance. Natural products offer a safer, multitargeted approach to cancer therapy. Curcuma caesia, a medicinal plant used in traditional medicine, was investigated for its anticancer potential. Using bioactivity-guided isolation, 14 fractions of its hexane extract were screened against CAL 27 oral cancer cells. Two fractions, NPSU HC and NPSU HJ, showed potent cytotoxicity with IC50 values of 40.78 and 45.60 µg/mL, respectively, and inhibited cell migration and colony formation. NPSU HC induced S- and G2-phase arrest, whereas NPSU HJ increased S-phase cell accumulation. Gas chromatography-mass spectrometry (GC-MS) analysis identified 14 phytochemicals, which was followed by the isolation of four sesquiterpenoids, furanodienone, zederone, germacrone, and curcumenol. Among them, furanodienone displayed the most potent activity with IC50 of 85.41 µM on CAL 27 cell line, causing G2-phase arrest and suppressing cancer cell proliferation. Molecular docking showed strong binding affinities, particularly for furanodienone, toward key oral cancer targets such as CDK6, HRAS, PIK3CA, and MYH9. Molecular dynamic (MD) simulations further confirmed the stable interaction between furanodienone and CDK6, supporting its potential as a promising oral cancer therapeutic candidate.