Home
Resources
Publications
Brazilin Induces FOXO3A-dependent Autophagic Cell Death by Disturbing Calcium Homeostasis in Osteosarcoma Cells

Brazilin Induces FOXO3A-dependent Autophagic Cell Death by Disturbing Calcium Homeostasis in Osteosarcoma Cells

Yan Kang, Peiheng He, Hua Wang, Yibiao Ye, Xing Li, Peigen Xie, Bowen Wu

Cancer Chemother Pharmacol. 2018 Sep;82(3):479-491.

PMID: 29987368

Abstract:

Purpose:
Osteosarcoma is a common primary malignant bone tumour, and its cure rate has stagnated over the past 25-30 years. Brazilin, a purified natural product from sappan wood (Caesalpinia sappan L.), has been proved to possess potent anti-cancer effects. In this study, we investigated the anti-cancer effect of brazilin on human osteosarcoma and elucidated the underlying mechanisms.
Methods:
We exposed MG-63 cells to different concentrations of brazilin (5, 10 and 20 µM) for 24 h. Western blotting, immunocytofluorescence, luciferase reporter assays, and RT-PCR were used to evaluate whether brazilin activates FOXO family-dependent autophagy.
Results:
Brazilin increased autophagic flux in the human osteosarcoma cell line MG-63, as evidenced by the upregulation of LC3-II and the downregulation of P62/SQSTM1. Moreover, the pharmacological or genetic blockade of autophagy decreased brazilin-induced cell death, indicating that brazilin triggered autophagic cell death in MG-63 cells. Specifically, brazilin induced FOXO3A(Ser7) phosphorylation, activated FOXO3A nuclear translocation and increased FOXO3A reporter activity, which contributed to the expression of autophagy-related genes and subsequently initiated autophagic cell death in MG-63 cells. Importantly, the increased expression and nuclear translocation of FOXO3A were tightly related to the disturbance of calcium homeostasis, which could be prevented by chelating intracellular calcium.
Conclusions:
Taken together, these data demonstrate that brazilin induces osteosarcoma cell death by inducing excessive autophagy, which is mediated through the Ca2+-FOXO3A pathway. Our study provides a new anti-tumour mechanism for brazilin treatment in osteosarcoma patients.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP474077-A	Brazilin		474-07-7	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: