Corydalis Saxicola Bunting Total Alkaloids Attenuate Walker 256-Induced Bone Pain and Osteoclastogenesis by Suppressing RANKL-Induced NF-κB and c-Fos/NFATc1 Pathways in Rats.

Linjie Ju,Zhixia Qiu,Fang Huang,Zhuoqun Li,Jun Cheng,Jiejie Wu,Ping Chen,Peipei Hu

doi:10.3389/fphar.2020.609119

Abstract

Metastatic bone pain is characterized by insufferable bone pain and abnormal bone structure. A major goal of bone cancer treatment is to ameliorate osteolytic lesion induced by tumor cells. Corydalis saxicola Bunting total alkaloids (CSBTA), the alkaloid compounds extracted from the root of C. saxicola Bunting, have been shown to possess anticancer and analgesic properties. In this study, we aimed to verify whether CSBTA could relieve cancer induced bone pain and inhibit osteoclastogenesis. The in vivo results showed that CSBTA ameliorated Walker 256 induced bone pain and osteoporosis in rats. Histopathological changes also supported that CSBTA inhibited Walker 256 cell-mediated osteolysis. Further in vitro analysis confirmed that CSBTA reduced the expression of RANKL and downregulate the level of RANKL/OPG ratio in breast cancer cells. Moreover, CSBTA could inhibit osteoclastogenesis by suppressing RANKL-induced NF-κB and c-Fos/NFATc1 pathways. Collectively, this study demonstrated that CSBTA could attenuate cancer induced bone pain via a novel mechanism. Therefore, CSBTA might be a promising candidate drug for metastatic bone pain patients.

Highlights

Metastatic bone pain is one of the most common forms of cancer induced unrelenting pain which significantly reduces patients’ living quality (Mao-Ying et al, 2006; Dai et al, 2017)
No detectable changes were observed in the body weights of Corydalis saxicola Bunting total alkaloids (CSBTA) treated or cancer induced bone pain (CIBP) rats compared with the Sham group
These findings indicated that CSBTA was able to ameliorate CIBP without obvious side effects

Summary

Introduction

Metastatic bone pain is one of the most common forms of cancer induced unrelenting pain which significantly reduces patients’ living quality (Mao-Ying et al, 2006; Dai et al, 2017). Tumor cells themselves do not destroy bone structure but rather secrete excessive receptor activator of nuclear factor κ-B ligand (RANKL). Cancer cells promote bone pain via an indirect osteoclastic acid-induced stimulation of nociceptors in bone as well as osteolytic lesion that, in turn, foster hyperalgesia through the release of inflammatory factors (Aielli et al, 2019). Studies suggested that administration of the OPG to osteosarcoma-bearing animals significantly decreased spontaneous pain behaviors without affecting the tumor size (Honore et al, 2000; Luger et al, 2001). To put it in a nutshell, osteoclast plays a pivotal role in CIBP

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