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

Area of Science:

• Natural Product Chemistry
• Cancer Biology
• Pharmacology

Background:

• Oral cancer is a significant global health issue, particularly in Southeast Asia.
• Current treatments face challenges like severe side effects and drug resistance.
• Natural products present a promising alternative for cancer therapy due to their multitargeted and safer profiles.

Purpose of the Study:

• To investigate the anticancer potential of Curcuma caesia against oral cancer.
• To identify and characterize active compounds from Curcuma caesia responsible for cytotoxic effects.
• To explore the molecular mechanisms underlying the anticancer activity of identified compounds.

Main Methods:

• Bioactivity-guided fractionation of Curcuma caesia hexane extract.
• Cytotoxicity assays using CAL 27 oral cancer cells.
• Cell cycle analysis, migration, and colony formation assays.
• Phytochemical analysis using Gas Chromatography-Mass Spectrometry (GC-MS).
• Isolation and characterization of sesquiterpenoids.
• Molecular docking and molecular dynamic simulations against oral cancer targets.

Main Results:

• Two fractions, NPSU HC and NPSU HJ, exhibited significant cytotoxicity (IC50 values 40.78 and 45.60 µg/mL) and inhibited cell migration and colony formation.
• NPSU HC induced S- and G2-phase arrest, while NPSU HJ caused S-phase accumulation.
• Four sesquiterpenoids, including furanodienone, were isolated.
• Furanodienone demonstrated potent activity (IC50 85.41 µM) against CAL 27 cells, inducing G2-phase arrest and suppressing proliferation.
• Molecular docking revealed strong binding affinities of furanodienone to CDK6, HRAS, PIK3CA, and MYH9.

Conclusions:

• Curcuma caesia possesses significant anticancer properties against oral cancer cells.
• Furanodienone is a key active compound with potent anti-oral cancer activity.
• Furanodienone's stable interaction with CDK6, confirmed by MD simulations, highlights its potential as a therapeutic candidate for oral cancer.