Osteosarcoma is one of the most malignant neoplasms in adolescents, and it generally develops multidrug resistance. Escin, a natural mixture of triterpene saponins isolated from Aesculus hippocastanum (horse chestnut), has demonstrated potent anti-tumour potential in vitro and in vivo. In the present study, we found that escin inhibited osteosarcoma proliferation in a dose- and time-dependent manner. Additionally, escin-induced apoptosis was evidenced by the increased expression of caspase-related proteins and the formation of apoptotic bodies. Escin also induced autophagy, with elevated LC3, ATG5, ATG12 and Beclin expression as well as autophagosome formation. Inhibition of escin-induced autophagy promoted apoptosis. Moreover, p38 mitogen-activated protein kinases (MAPKs) and reactive oxygen species (ROS) were activated by escin. A p38 MAPK inhibitor partially attenuated the autophagy and apoptosis triggered by escin, but a ROS scavenger showed a greater inhibitory effect. Finally, the therapeutic efficacy of escin against osteosarcoma was demonstrated in an orthotopic model. Overall, escin counteracted osteosarcoma by inducing autophagy and apoptosis via the activation of the ROS/p38 MAPK signalling pathway; these findings provide evidence for escin as a novel and potent therapeutic for the treatment of osteosarcoma.

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Adipose-derived stem cells (ADSCs)-based tissue engineering was a promising method to treat intervertebral disc degeneration. Type II collagen is a native component in the nucleus pulposus (NP), and has the ability to promote ADSCs to differentiate into NP-like cells. In this article, we aimed to establish a genipin-cross-linked three-dimensional (3D) type II collagen scaffold, and determine the biological effects of the scaffold on ADSCs differentiating into a NP-like phenotype. Different concentrations of genipin were used to cross-link the 3D type II collagen scaffold. Microstructure, surface topography, mechanical strength, porosity, swelling property, and biological stability of the scaffolds were detected to evaluate the scaffold properties. Cell proliferation, gene and protein expression were measured to access the biological effects of the scaffolds on ADSCs, and the related molecular mechanism was investigated. Cross-linking by genipin increased the stability of the type II collagen scaffolds, but deformed the configuration of scaffolds and changed the intrinsic properties of type II collagen. scaffold cross-linked with 0.1% genipin improved the biostability on the basis of maintaining the configuration of scaffold. In addition, the 0.1% genipin-cross-linked scaffold promoted ADSCs proliferation and differentiation into NP-like cells, along with the increasing gene and protein expressions of Sonic Hedgehog (Shh). All these results suggested that 0.1% genipin was the optimal concentration to establish a bio-stable 3D type II collagen scaffold, which inducing ADSC proliferation and differentiation toward a NP-like phenotype through the activation of Shh signaling pathway. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1258-1268, 2018.