Metabolomic Approach in Anticancer Biomarker Discovery from Foliose Lichens

Area of Science:

• Natural Product Chemistry
• Computational Chemistry
• Biomarker Discovery

Background:

• Lichens are a known source of pharmacologically active compounds, including potential anticancer agents.
• Traditional lichen bioprospecting faces biomass constraints.
• Advanced metabolomic and computational approaches offer novel solutions for discovering lichen-derived anticancer compounds.

Purpose of the Study:

• To discover anticancer biomarkers from Indonesian lichens using cutting-edge metabolomics and computational techniques.
• To overcome biomass limitations associated with traditional bioprospecting methods.
• To identify novel therapeutic compounds for cervical cancer treatment.

Main Methods:

• Seven lichen crude extracts were screened for cytotoxicity against HeLa cervical cancer cells using MTT assays.
• Gas chromatography-mass spectrometry (GC-MS) was employed for secondary metabolite profiling.
• Orthogonal partial least-squares-discriminant analysis (OPLS-DA) and structure-based computational docking were used to identify potential anticancer biomarkers.

Main Results:

• MTT assays revealed varying levels of cytotoxicity among the lichen extracts.
• OPLS-DA analysis successfully separated extracts into distinct cytotoxic groups.
• GC-MS and OPLS-DA identified 13 compounds from Parmelia caroliniana and 12 from Physcia cf. millegrana as biomarker candidates.
• Compound 4 (6-amino-3,4,7-triphenylpyrido[2',3':4,5]thieno[2,3-c]pyridazine) from P. caroliniana exhibited the highest binding affinity to target proteins BCL-2, AKT-1, MCL-1, and BRAF.

Conclusions:

• Compound 4 from Parmelia caroliniana is identified as a promising anticancer biomarker against HeLa cancer cells.
• The established metabolomic protocol can be applied for biomarker discovery in other medicinal plants.
• Further in vitro and in vivo studies are warranted to explore the therapeutic potential of compound 4.