Flavones and Aminoflavones Show Anti-Cancer Effects in Two Studies

Two studies report anti-cancer activity for flavone compounds. One study found that 3-Hydroxyflavone inhibited oral squamous cell carcinoma (OSCC) cell proliferation and improved survival by modulating the AGEs/RAGE/NF-κB signaling pathway. Another study showed that synthetic flavones and aminoflavones increased the cytotoxicity of natural killer (NK) cells against human non-small cell lung cancer cells.

In the first study, researchers investigated whether 3-Hydroxyflavone inhibits OSCC by modulating miR-142-5p within the AGEs/RAGE/NF-κB axis. The expression of p65 and miR-142-5p was analyzed in OSCC tissues and Tca8113 cells. TargetScan prediction and dual-luciferase reporter assays confirmed that p65 is a direct target of miR-142-5p. The effects of 3-Hydroxyflavone on OSCC cells were evaluated using MTT and colony formation assays. OSCC tissues showed increased p65 nuclear translocation and decreased miR-142-5p levels. The miR-142-5p directly inhibited p65. 3-Hydroxyflavone treatment suppressed OSCC cell proliferation and colony formation by upregulating miR-142-5p and inhibiting the AGEs/RAGE/NF-κB pathway. High p65 expression correlated with poor survival, while 3-Hydroxyflavone treatment reduced p65 and improved survival. The study concluded that 3-Hydroxyflavone inhibits OSCC proliferation and enhances survival by upregulating miR-142-5p, which suppresses AGEs/RAGE/NF-κB signaling, suggesting a novel therapeutic strategy.

The second study determined that synthetic flavones and aminoflavones modulate the cytotoxicity of natural killer (NK) cells against lung cancer cells. Flavones 2, 3, and 6 and aminoflavone 8 were shown to increase the cytotoxicity of NK-92MI cells against A549 lung cancer cells without adversely affecting MRC5 normal cells. Aminoflavone 8 enhanced NK-92MI cell cytotoxicity, as evidenced by elevated expression of cytotoxic effectors such as IFN-γ, perforin, and granzyme B. Aminoflavone 8 also inhibited STAT3 phosphorylation in A549 lung cancer and NK-92MI cells under co-culture conditions. Moreover, aminoflavone 8 exhibited anti-tumour effects in a lung cancer xenograft mouse model. Combined therapy with aminoflavone 8 and NK-92MI cells had synergistic anti-tumour effects without liver or kidney toxicity. The analysis revealed that the amino group in the C6 position of aminoflavone 8 was crucial to the enhanced cytotoxicity of NK cells. These findings suggest that aminoflavone 8 can potentiate NK cell cytotoxicity against lung cancer cells, highlighting its potential as a novel therapeutic agent for the treatment of lung cancer.