Osthole inhibits bone metastasis of breast cancer

// Chunyu Wu 1, * , Zhenping Sun 1, * , Baofeng Guo 1 , Yiyi Ye 2 , Xianghui Han 2 , Yuenong Qin 1 and Sheng Liu 1, 2 1 Department of Breast Surgery (Integrated Traditional and Western Medicine), Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China 2 Pharmacology Laboratory of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China * These authors have contributed equally to this work Correspondence to: Sheng Liu, email: sliu_tcm@163.com Yuenong Qin, email: frank_yching@aliyun.com Keywords: osthole, Cnidium monnieri (L.) Cusson , coumarin, breast cancer, bone metastasis Received: September 06, 2016     Accepted: March 21, 2017     Published: April 11, 2017 ABSTRACT Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.) , exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potential mechanism of this inhibition. In the murine model of breast cancer osseous metastasis, mice that received osthole developed significantly less bone metastases and displayed decreased tumor burden when compared with mice in the control group. Osthole inhibited breast cancer cell growth, migration, and invasion, and induced apoptosis of breast cancer cells. Additionally, it also regulated OPG/RANKL signals in the interactions between bone cells (osteoblasts and osteoclasts) and cancer cells. Besides, it also inhibited TGF-β/Smads signaling in breast cancer metastasis to bone in MDA-231BO cells. The results of this study suggest that osthole has real potential as a therapeutic candidate in the treatment of breast cancer patients with bone metastases.