Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF‐1/SOX9 Axis

Abstract

Chondrosarcoma is the second most malignant bone tumor with poor prognosis and limited treatment options. Thus, development of more effective treatments has become urgent. Recently, natural compounds derived from medicinal plants have emerged as promising therapeutic options via targeting multiple key cellular molecules. Andrographolide (Andro) is such a compound, which has previously been shown to induce cell cycle arrest and apoptosis in several human cancers. However, the molecular mechanism through which Andro exerts its anti-cancer effect on chondrosarcoma remains to be elucidated. In the present study, we showed that Andro-induced G2/M cell cycle arrest of chondrosarcoma by fine-tuning the expressions of several cell cycle regulators such as p21, p27, and Cyclins, and that prolonged treatment of cells with Andro caused pronounced cell apoptosis. Remarkably, we found that SOX9 was highly expressed in poor-differentiated chondrosarcoma, and that knockdown of SOX9 suppressed chondrosarcoma cell growth. Further, our results showed that Andro dose-dependently down-regulated SOX9 expression in chondrosarcoma cells. Concomitantly, an inhibition of T cell factor 1 (TCF-1) mRNA expression and an enhancement of TCF-1 protein degradation by Andro were observed. In contrast, the expression and subcellular localization of β-catenin were not altered upon the treatment of Andro, suggesting that β-catenin might not function as the primary target of Andro. Additionally, we provided evidence that there was a mutual regulation between TCF-1 and SOX9 in chondrosarcoma cells. In conclusion, these results highlight the potential therapeutic effects of Andro in treatment of chondrosarcoma via targeting the TCF-1/SOX9 axis. J. Cell. Biochem. 118: 4575-4586, 2017. © 2017 Wiley Periodicals, Inc.

Transcriptional regulation of Runx2 by HSP90 controls osteosarcoma apoptosis via the AKT/GSK‐3β/β‐catenin signaling

“…At the end of various treatments, Saos‐2 and U2 OS cells were harvested by trypsinization, and were washed twice with ice‐cold PBS. The apoptotic cells were determined by flow cytometry using Annexin V‐APC/7‐amino‐actinomycin D (7‐AAD) Apoptosis Detection Kit (KeyGEN Biotechnology, Nanjing, China) . The results were analyzed by FlowJo 7.6.5 software (FlowJo Enterprise, Ashland, KY).…”

“…The apoptotic cells were determined by flow cytometry using Annexin V-APC/7-amino-actinomycin D (7-AAD) Apoptosis Detection Kit (KeyGEN Biotechnology, Nanjing, China). 20 The results were analyzed by FlowJo 7.6.5 software (FlowJo Enterprise, Ashland, KY).…”

Andrographolide inhibits proliferation and induces cell cycle arrest and apoptosis in human melanoma cells

“…It has been proved that Andro possess various biological activities such as anti-inflammation, anti-infection, immune system regulation, anti-cardiovascular disease, and anticancer effects (13)(14)(15). Previous studies have shown that Andro exhibited potential antitumor activity in various malignancies, including gastric cancer (16), chondrosarcoma (17) and colorectal cancer (18). However, whether Andro suppresses the growth of human melanoma cells and its potential molecular mechanisms were still not well investigated.…”

Inhibiting ROS-TFEB-Dependent Autophagy Enhances Salidroside-Induced Apoptosis in Human Chondrosarcoma Cells

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