Lee Sun Kyoung, Park Kwang-Kyun, Kim Ki Rim, Kim Hyun-Jeong, Chung Won-Yoon
Department of Oral Biology, Oral Cancer Research Institute, BK21 PLUS Project, Yonsei University College of Dentistry, Korea; Department of Applied Life Science, Yonsei University Graduate School, Seoul, Korea.
Department of Dental Hygiene, College of Science and Technology, Kyungpook National University, Sangju, Korea.
J Cancer Prev. 2015 Dec;20(4):281-6. doi: 10.15430/JCP.2015.20.4.281. Epub 2015 Dec 30.
Bone destruction induced by the metastasis of breast cancer cells is a frequent complication that is caused by the interaction between cancer cells and bone cells. Receptor activator of nuclear factor kappa-B ligand (RANKL) and the endogenous soluble RANKL inhibitor, osteoprotegerin (OPG), directly play critical roles in the differentiation, activity, and survival of osteoclasts. In patients with bone metastases, osteoclastic bone resorption promotes the majority of skeletal-related events and propagates bone metastases. Therefore, blocking osteoclast activity and differentiation via RANKL inhibition can be a promising therapeutic approach for cancer-associated bone diseases. We investigated the potential of isoliquiritigenin (ISL), which has anti-proliferative, anti-angiogenic, and anti-invasive effects, as a preventive and therapeutic agent for breast cancer cell-induced bone destruction. ISL at non-toxicity concentrations significantly inhibited the RANKL/OPG ratio by reducing the production of RANKL and restoring OPG production to control levels in hFOB1.19 cells stimulated with conditioned medium (CM) of MDA-MB-231 cells. In addition, ISL reduced the expression of cyclooxygenase-2 in hFOB1.19 cells stimulated by CM of MDA-MB-231 cells. Therefore, ISL may have inhibitory potential on breast cancer-induced bone destruction.
乳腺癌细胞转移引起的骨破坏是一种常见并发症，由癌细胞与骨细胞之间的相互作用所致。核因子κB受体活化因子配体（RANKL）和内源性可溶性RANKL抑制剂骨保护素（OPG）直接在破骨细胞的分化、活性和存活中起关键作用。在骨转移患者中，破骨细胞性骨吸收促进了大多数骨相关事件并促进骨转移。因此，通过抑制RANKL来阻断破骨细胞活性和分化可能是治疗癌症相关骨疾病的一种有前景的治疗方法。我们研究了具有抗增殖、抗血管生成和抗侵袭作用的异甘草素（ISL）作为乳腺癌细胞诱导的骨破坏的预防和治疗剂的潜力。在无毒浓度下，ISL通过降低RANKL的产生并将OPG的产生恢复到用MDA-MB-231细胞条件培养基（CM）刺激的hFOB1.19细胞中的对照水平，显著抑制了RANKL/OPG比值。此外，ISL降低了用MDA-MB-231细胞CM刺激的hFOB1.19细胞中环氧合酶-2的表达。因此，ISL可能对乳腺癌诱导的骨破坏具有抑制潜力。
