The role of Luteolin, Naringenin, and Scutellarin in breast cancer by inhibition of HDAC4/HDAC8

The side effects associated with conventional anti-cancer therapies call for safer and more effective alternatives. Flavonoids are a class of polyphenolic compounds well documented to possess antioxidant, anti-inflammatory, and anticancer properties. This study investigates the bioactivity of three flavonoids, namely Luteolin, Naringenin, and Scutellarin, with a focus on identification and validation of their molecular targets in human breast cancer. Potential targets were screened using the ePharmaLib database, followed by in silico structure-based pharmacophore mapping and molecular docking. Further confirmation was achieved through in vitro biochemical assays and cell-based studies. HDAC4 and HDAC8 assays validated the enzyme inhibitions of flavonoids, particularly Luteolin. In breast cancer cell lines, apoptosis was induced by flavonoids, as viewed by fluorescence microscopy and flow cytometry. Among these, Luteolin exhibited the most potent cytotoxicity. Antioxidant activity assays showed that luteolin and Scutellarin strongly scavenged radicals similar to quercetin. Naringenin and Luteolin significantly enhanced catalase activity. In THP-1-derived macrophages, all three flavonoids significantly suppressed LPS-induced inflammation with reduced expression of pro-inflammatory cytokines at both RNA and protein levels. Collectively, results clearly pinpoint that Luteolin, Naringenin, and Scutellarin may be explored as therapeutic possibilities since they exhibit strong anticancer, antioxidant, and anti-inflammatory properties.