Galangin inhibits human osteosarcoma cells growth by inducing transforming growth factor-β1-dependent osteogenic differentiation.
Osteosarcoma is the most common primary malignancy of the musculoskeletal system, and is associated with excessive proliferation and poor differentiation of osteoblasts. Currently, despite the use of traditional chemotherapy and radiotherapy, no satisfactory and effective agent has been developed to treat the disease. Herein, we found that a flavonoid natural product, galangin, could significantly attenuate human osteosarcoma cells proliferation, without causing obvious cell apoptosis. Moreover, galangin enhanced the expression of osteoblast differentiation markers (collagen type I, alkaline phosphatase, osteocalcin and osteopontin) remarkably and elevated the alkaline phosphatase activity in human osteosarcoma cells. And galangin could also attenuated osteosarcoma growth in vivo. These bioactivities of galangin resulted from its selective activation of the transforming growth factor (TGF)-β1/Smad2/3 signaling pathway, which was demonstrated by pathway blocking experiments. These findings suggested that galangin could be a promising agent to treat osteosarcoma. In addition, targeting TGF-β1 to induce osteogenic differentiation might represent a novel therapeutic strategy to treat osteosarcoma with minimal side effects.
Department of Orthopedic Surgery, The Second People's Hospital of Wuhu, Anhui, China. Electronic address: 18155317015@163.com.
Chunhong
C
Liu
Department of Orthopedic Surgery, The People's Hospital of Fuyang, Anhui, China. Electronic address: mz20100104@outlook.com.
Mingming
M
Ma
Department of Orthopedic Surgery, The Second People's Hospital of Wuhu, Anhui, China. Electronic address: drjundezhang@126.com.
Junde
J
Zhang
Department of Orthopedic Surgery, The Second People's Hospital of Wuhu, Anhui, China. Electronic address: guishaoliu@163.com.
Shaoliu
S
Gui
Department of Orthopedic Surgery, The Second People's Hospital of Wuhu, Anhui, China. Electronic address: johnchan70@126.com.
Xiaohai
X
Zhang
Department of Orthopedic Surgery, The Second People's Hospital of Wuhu, Anhui, China. Electronic address: dr.shuangtaoxue@hotmail.com.
Shuangtao
S
Xue
D000469:Alkaline Phosphatase / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D014408:Biomarkers, Tumor; D005419:Flavonoids; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; C037032:galangin; D000469:Alkaline Phosphatase
Galangin; Osteogenic differentiation; Osteosarcoma; TGF-β1/Smad2/3; Therapy