Andrographolide Induces Cell Cycle Arrest and Apoptosis of Chondrosarcoma by Targeting TCF‐1/SOX9 Axis. Issue 12 (7th September 2017)

• Record Type: Journal Article
• Authors: Zhang, Huan‐Tian; Yang, Jie; Liang, Gui‐Hong; Gao, Xue‐Juan; Sang, Yuan; Gui, Tao; Liang, Zu‐Jian; Tam, Man‐Seng; Zha, Zhen‐Gang
• Is Part Of: Journal of cellular biochemistry. Volume 118:Issue 12(2017)
• Page Start: 4575
• Page End: 4586
• Publication Date: 2017-09-07
• Subjects: ANDROGRAPHOLIDE -- CELL CYCLE ARREST -- APOPTOSIS -- TCF‐1 -- SOX9 -- CHONDROSARCOMA; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.26122
• Languages: English
• ISSNs: 0730-2312

Abstract

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. Abstract : Andrographolide (Andro) induces G2/M cell cycle arrest and apoptosis of chondrosarcoma cells. SOX9 is predominantly expressed in the nucleus of chondrosarcoma tissue and its expression level is positively correlated with pathological grades of chondrosarcoma. Andro plays dual roles in regulation of TCF‐1 expression, through suppressing mRNA level and enhancing proteasomal degradation in particular. TCF‐1, but not β‐catenin, mediates the regulation of SOX9 by Andro in chondrosarcoma cells.