α-Mangostin Induces Apoptosis in Human Chondrosarcoma Cells through Downregulation of ERK/JNK and Akt Signaling Pathway

Chondrosarcoma is a malignant primary bone tumor that is resistant to chemotherapy and radiation therapy. alpha-Mangostin, a component of Garcinia mangostana Linn, is a xanthone derivative shown to have antioxidant and antitumor properties. This study is the first to investigate anticancer effects of alpha-mangostin in the human chondrosarcoma cell line SW1353. We showed that alpha-mangostin inhibited cell proliferation of SW1353 cells in a time- and dose-dependent manner by using the trypan blue exclusion method. Hoechst 33342 nuclear staining and nucleosomal DNA-gel electrophoresis revealed that alpha-mangostin could induce nuclear condensation and fragmentation, typically seen in apoptosis. Flow cytometry using Annexin V/PI double staining assessed apoptosis, necrosis and viability. alpha-Mangostin activated caspase-3, -8, -9 expression, decreased Bcl-2 and increased Bax. This promotes mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm. In addition, total and phosphorylated ERK and JNK were downregulated in alpha-mangostin-treated SW1353 cells but no changes in p38. alpha-Mangostin also decreased phosphorylated Akt without altering total Akt. These results suggest that alpha-mangostin inhinbited cell proliferation and induced apoptosis through downregulation of ERK, JNK and Akt signaling pathway in human chondrosarcoma SW1353 cells.