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.
School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Jen-Yu
JY
Hung
Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
Wei-An
WA
Chang
Division of Pulmonary and Critical Care Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
Ying-Ming
YM
Tsai
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Ya-Ling
YL
Hsu
Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Hung-Hsing
HH
Chiang
Division of Chest Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, R.O.C.
Shah-Hwa
SH
Chou
School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Ming-Shyan
MS
Huang
Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan, R.O.C.
Po-Lin
PL
Kuo
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001564:Benzo(a)pyrene / Q000633:toxicity; D001859:Bone Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D001862:Bone Resorption; D002289:Carcinoma, Non-Small-Cell Lung / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D053244:Osteoprotegerin / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
D000970:Antineoplastic Agents; D002867:Chromones; D005419:Flavonoids; D016209:Interleukin-8; D053244:Osteoprotegerin; D044162:Parathyroid Hormone-Related Protein; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D001564:Benzo(a)pyrene; C469689:tricetin; D016173:Macrophage Colony-Stimulating Factor