Icaritin inhibits lung cancer-induced osteoclastogenesis by suppressing the expression of IL-6 and TNF-a and through AMPK/mTOR signaling pathway. Issue 10 (November 2020)

• Record Type: Journal Article
• Authors: Zhao, Xueqiang; Lin, Yun; Jiang, Bijia; Yin, Jianhua; Lu, Chunlan; Wang, Juan; Zeng, Jinrong
• Is Part Of: Anti-cancer drugs. Volume 31:Issue 10(2020)
• Publication Date: 2020-11
• Subjects: AMPK -- icaritin -- lung cancer -- mTOR -- one metastasis -- osteoclastogenesis; Antineoplastic agents -- Periodicals; Cancer -- Chemotherapy -- Periodicals; Antineoplastic Agents -- therapeutic use -- Periodicals; Drug Therapy -- Periodicals; 616.994061
• DOI: 10.1097/CAD.0000000000000976
• Languages: English
• ISSNs: 0959-4973

Abstract

Abstract : Bone metastasis is one of the common phenomena in the late stage of lung cancer. Inhibition of bone metastasis can improve the survival of lung cancer patients. However, the current drugs for the treatment of bone metastasis have shown little effect on overall survival. Therefore, there is an urgent necessity to identify novel drugs capable of preventing and treating bone metastasis of lung cancer. Our study determined that icaritin (ICT) can inhibit lung cancer-mediated osteoclastogenesis and induce the apoptosis of osteoclasts. Exposure to ICT increased the activation of adenosine 5'-monophosphate-activated protein kinase (AMPK), reduced the activation of mammalian target of rapamycin (mTOR) and decreased the expression of bcl-2. The bioactivity of ICT on osteoclastogenesis was associated with the regulation of the AMPK/mTOR signaling pathway. Blocking AMPK significantly increased osteoclast differentiation, decreased osteoclast apoptosis and canceled the effects of ICT on the phosphorylation of AMPK as well as the inhibition of mTOR and bcl-2. Furthermore, ICT decreased the levels of IL-6 and TNF-α in osteoclasts, while the AMPK inhibitor compound C significantly abolished the inhibitory effects of ICT on IL-6 and TNF-α. Thus, the present study demonstrated that ICT may be a potential natural agent for the treatment of bone metastasis in patients with lung cancer.