Bisphosphonate enhances TRAIL sensitivity to human osteosarcoma cells via death receptor 5 upregulation

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily of cytokines, is one of the most promising candidates for cancer therapeutics. However, many osteosarcomas are resistant to TRAIL. Bisphosphonates are very effective in the treatment of bone problems associated with malignancies; the antitumor effects are due to the inhibition of protein prenylation that is essential for cell function and survival. The purpose of this study was to determine the effects of bisphosphonates on TRAIL-resistant MG 63 human osteosarcoma cells. The cells showed no response to TRAIL alone; however, pre-treatment with bisphosphonates significantly increased TRAIL-mediated apoptosis and cellular activation of caspase-3. Bisphosphonates significantly induced mRNA and protein expression of the TRAIL receptor, DR5. Bisphosphonates induced protein unprenylation in MG 63 cells; in addition, co-treatment with TRAIL also significantly increased protein unprenylation. Blocking of protein unprenylation using geranylgeraniol attenuated the cellular responses, including cell apoptosis and protein unprenylation induced by bisphosphonates and TRAIL. This is the first study to demonstrate that bisphosphonates markedly enhanced TRAIL-induced apoptosis in human osteosarcoma cells. These findings suggest that bisphosphonates may be a new and effective anticancer treatment with TRAIL proteins for TRAIL-resistant cancer cells.

Establishment and Characterization of Chromosome Aberrations in Hman Colangiocarcinoma Cell Line, PCK1 / 대한해부학회지

The analysis of recurring chromosome aberrations has become an integral part of the diagnostic and prognostic workup of many human cancers, and their molecular analyses have facilitated the identification of genes related to the pathogenesis of cancer. Cholangiocarcinoma (CC), a malignant neoplasm of the biliary epithelium, is usually fatal because of the difficulty in early diagnosis and unavailability of effective therapy. Furthermore, little is known about the genetics and biology of CC. Only few reports concerning cytogenetic studies of CC have been published and few cell lines have been established. We recently established CC cell line, designated as PCK1. The purpose of this study is to establish in detail karyotype of PCK1 cell line. The origins of the unidentified marker chromosomes were analyzed by G-banding, cross species color banding (RxFISH), and human chromosome-specific painting. In PCK1 cell line, gains involved chromosomes and chromosome regions, 4, 5, 9, 12, 16, 21, 1q, 7q11-q22, 8q, 12p, 14q11-q22, 15q21-qter, 17p11-qter, and 18p. Losses involved Y, 7q31-qter, 8p, 14q23-qter, 17p12-pter, and 18q. Established PCK1 cell line will be able to use the basic research of cholangiocarcinoma and the abnormal chromo-somes may be the candidate regions for isolation of the genes related to CC.