Antitumor effect of resveratrol on chondrosarcoma cells via phosphoinositide 3-kinase/AKT and p38 mitogen-activated protein kinase pathways.
Chondrosarcoma is one of the most common types of primary bone cancer that develops in cartilage cells. Resveratrol (Res), a natural polyphenol compound isolated from various fruits, has a suppressive effect on various human malignancies. It has been shown that Res inhibits matrix metalloproteinase (MMP)-induced differentiation in chondrosarcoma cells. However, the effects of Res on cell proliferation, apoptosis and invasion of chondrosarcoma cells, as well as the underlying mechanisms, remain largely unknown. To the best of our knowledge, the present study showed for the first time that Res inhibited proliferation and induced apoptosis in chondrosarcoma cells in a dose-dependent manner. Furthermore, it was shown that Res also suppressed chondrosarcoma cell invasion in a dose-dependent manner, probably via the inhibition of MMP2 and MMP9 protein expression. Molecular mechanism investigations revealed that Res could inhibit the activity of phosphoinositide 3-kinase/AKT and p38 mitogen-activated protein kinase signaling pathways, which has been demonstrated to be important in the regulation of proliferation, apoptosis and invasion in various cancer cell types. In conclusion, this study suggests that Res may serve as a promising agent for the treatment of chondrosarcoma.
Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Zixun
Z
Dai
Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Pengfei
P
Lei
Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Jie
J
Xie
Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Yihe
Y
Hu
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol