title: α-Mangostin induces apoptosis in human chondrosarcoma cells through downregulation of ERK/JNK and Akt signaling pathway.
abstract: Chondrosarcoma is a malignant primary bone tumor that is resistant to chemotherapy and radiation therapy. α-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 α-mangostin in the human chondrosarcoma cell line SW1353. We showed that α-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 α-mangostin could induce nuclear condensation and fragmentation, typically seen in apoptosis. Flow cytometry using Annexin V/PI double staining assessed apoptosis, necrosis and viability. α-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 α-mangostin-treated SW1353 cells but no changes in p38. α-Mangostin also decreased phosphorylated Akt without altering total Akt. These results suggest that α-mangostin inhinbited cell proliferation and induced apoptosis through downregulation of ERK, JNK and Akt signaling pathway in human chondrosarcoma SW1353 cells.
authors: Department of Biochemistry, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand.
authors: Aungkana
authors: A
authors: Krajarng
authors: Yukio
authors: Y
authors: Nakamura
authors: Sunit
authors: S
authors: Suksamrarn
authors: Ramida
authors: R
authors: Watanapokasin
mesh_terms: D000972:Antineoplastic Agents, Phytogenic; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002813:Chondrosarcoma / Q000473:pathology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D044004:Xanthones; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C021053:mangostin