Department of Oral Biology and Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, 120-752, Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, 120-749, Korea.
Phytother Res. 2013 Dec;27(12):1776-83. doi: 10.1002/ptr.4930. Epub 2013 Feb 11.
The aim of this study was to determine whether the ethanol extract of roasted licorice (rLE) could inhibit breast cancer-mediated bone destruction. rLE treatment reduced the viability of MDA-MB-231 human metastatic breast cancer cells but did not show any cytotoxicity in hFOB1.19 human osteoblastic cells and murine bone marrow-derived macrophages (BMMs). rLE inhibited expression and secretion of receptor activator of nuclear factor κB ligand (RANKL) as well as the mRNA and protein expression of cyclooxygenase-2 in osteoblastic cells exposed to the conditioned medium of breast cancer cells. rLE dramatically inhibited RANKL-induced osteoclastogenesis in BMMs, thereby reducing osteoclast-mediated pit formation. Moreover, treatment with licochalcone A and isoliquiritigenin as the active components, whose contents are increased by the roasting process, remarkably suppressed RANKL-induced osteoclast formation in BMMs, respectively. Furthermore, orally administered rLE substantially blocked tumor growth and bone destruction in mice inoculated with breast cancer cells in the tibiae. Serum levels of tartrate-resistant acid phosphatase and C-terminal cross-linking telopeptide of type I collagen and trabecular bone morphometric parameters were reversed to almost the same levels as the control mice by the rLE treatment. In conclusion, rLE may be a beneficial agent for preventing and treating bone destruction in patients with breast cancer.
本研究旨在确定经烘烤甘草的乙醇提取物（rLE）是否能抑制乳腺癌引起的骨破坏。rLE 处理降低了 MDA-MB-231 人转移性乳腺癌细胞的活力，但在 hFOB1.19 人成骨细胞和鼠骨髓来源的巨噬细胞（BMM）中没有显示出任何细胞毒性。rLE 抑制了暴露于乳腺癌细胞条件培养基的成骨细胞中核因子κB 受体激活剂配体（RANKL）的表达和分泌，以及环氧合酶-2 的 mRNA 和蛋白表达。rLE 显著抑制了 BMM 中 RANKL 诱导的破骨细胞生成，从而减少了破骨细胞介导的陷窝形成。此外，作为活性成分的甘草查尔酮 A 和异甘草素，其含量因烘烤过程而增加，分别显著抑制了 BMM 中 RANKL 诱导的破骨细胞形成。此外，口服 rLE 可显著抑制在胫骨中接种乳腺癌细胞的小鼠的肿瘤生长和骨破坏。rLE 处理将血清中抗酒石酸酸性磷酸酶和 I 型胶原 C 末端交联肽以及小梁骨形态计量学参数的水平逆转至接近对照小鼠的水平。总之，rLE 可能是预防和治疗乳腺癌患者骨破坏的有益药物。
