Tricetin, a dietary flavonoid, suppresses benzo(a)pyrene‑induced human non‑small cell lung cancer bone metastasis.

This is the first study to demonstrate that benzo(a)-pyrene (BaP) was able to enhance the production of parathyroid hormone‑related protein (PTHrP) by human non‑small cell lung cancer H460 cells. Such effect would further contribute to bone metastasis of lung cancer by increasing osteoclastogenesis. This study is also the first to reveal that tricetin (TCN), a flavonoid derivative found in Myrtaceae pollen and Eucalyptus honey, was able to reverse BaP‑mediated bone resorption activity of lung cancer cells. Human non‑small cell lung cancer H460 cells were treated with BaP to generate conditioned medium. When osteoblasts were cultured with BaP‑H460‑CM, their expression of osteoclastogenesis activator macrophage colony‑stimulating factor (M‑CSF) and receptor activator of nuclear factor κB ligand (RANKL) was increased. BaP‑H460‑CM reduced the production of osteoprotegerin (OPG), an osteoclastogenesis inhibitor, in osteoblasts. Osteoclastogenesis and bone resorption activity of H460 cells were increased by BaP‑H460‑CM. With BaP‑mediated PTHrP upregulation, IL‑8 secretion in H460 cells was increased contributing to human non‑small cell lung cancer‑mediated osteoclast differentiation and bone resorption. Moreover, TCN suppressed BaP‑mediated bone resorption. Therefore, TCN may be a novel agent for treatment of non‑small cell lung cancer patients with bone metastasis.