Plumbagin inhibits breast tumor bone metastasis and osteolysis by modulating the tumor-bone microenvironment

Current Molecular Medicine
Z LiM Liu

Abstract

Bone metastasis is a common and serious consequence of breast cancer. Bidirectional interaction between tumor cells and the bone marrow microenvironment drives a so-called 'vicious cycle' that promotes tumor cell malignancy and stimulates osteolysis. Targeting these interactions and pathways in the tumor-bone microenvironment has been an encouraging strategy for bone metastasis therapy. In the present study, we examined the effects of plumbagin on breast cancer bone metastasis. Our data indicated that plumbagin inhibited cancer cell migration and invasion, suppressed the expression of osteoclast-activating factors, altered the cancer cell induced RANKL/OPG ratio in osteoblasts, and blocked both cancer cell- and RANKL-stimulated osteoclastogenesis. In mouse model of bone metastasis, we further demonstrated that plumbagin significantly repressed breast cancer cell metastasis and osteolysis, inhibited cancer cell induced-osteoclastogenesis and the secretion of osteoclast-activating factors in vivo. At the molecular level, we found that plumbagin abrogated RANKL-induced NF-κB and MAPK pathways by blocking RANK association with TRAF6 in osteoclastogenesis, and by inhibiting the expression of osteoclast-activating factors through the...Continue Reading

Citations

Nov 28, 2012·Journal of the National Cancer Institute·Yuanzhang FangMingyao Liu
Oct 21, 2016·The Journal of Biological Chemistry·Sisi LiuXin-Hua Feng
Mar 10, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Haseeb ZubairAjay Pratap Singh
Apr 4, 2021·International Journal of Molecular Sciences·Sevinj SultanliKatharina F Kubatzky
Nov 6, 2020·Seminars in Cancer Biology·Mohammad Fahad UllahFaisel M Abuduhier
Jul 6, 2021·Journal of Food Biochemistry·Priyanshi RanaChandi C Mandal

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