Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 62, Issue 49, Pages 11933-11940Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jf5042905
Keywords
Cassia tora; obtusifolin; phthalate; PTHrP; osteoclastogenesis
Funding
- National Science Council of Taiwan [NSC 102-2628-B-037-002-MY3, NSC 102-2632-B-037-001-MY3, NSC 102-2314-B-037-035-MY3]
- Kaohsiung Medical University [KMU-DT103008, KMU-TP103A15]
- Excellence for Cancer Research Center Grant, Ministry of Health and Welfare, Executive Yuan, Taipei, Taiwan [MOHW 103-TD-B-111-05]
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This study is the first to demonstrate that parathyroid hormone-related protein (PTHrP), produced by human breast cancer cells after exposure to phthalate esters, contributes to bone metastasis by increasing osteoclastogenesis. This is also the first to reveal that obtusifolin reverses phthalate esters-mediated bone resorption. Human breast cancer cells were treated with dibutyl phthalate (DBP), harvested in conditioned medium, and cultured to osteoblasts or osteoclasts. Cultures of osteoblasts with DBP-MDA-MB-231-CM increased the osteoclastogenesis activator RANKL (receptor activator of nuclear factor ?-B ligand) and M-CSF (macrophage colony-stimulating factor). PTHrP was secreted in MDA-MB-231 cells. DBP-MDA-MB-231-CM reduced osteoblasts to produce osteoprotegerin, an osteoclastogenesis inhibitor, while DBP mediated PTHrP up-regulation, increasing IL-8 secretion in MDA-MB-231 and contributing to breast cancer-mediated osteoclast differentiation and bone resorption. Obtusifolin, a major bioactive compound present in Cassia tora L., suppressed phthalate esters-mediated bone resorption. Therefore, obtusifolin may be a novel anti-breast-cancer bone metastasis agent.
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