Apoptosis ligand plus etoposide selectively kills bone tumor cells

Bone tumor cells, which are resistant to killing by TRAIL/Apo2L (tumor necrosis factor-related apoptosis-inducing ligand), succumb to exogenous recombinant TRAIL/Apo2L when co-treated with etoposide, investigators from Germany have found.

“Although TRAIL/Apo2L preferably induces apoptosis in tumor cells without toxicity in normal cells, many tumor cell types display TRAIL/Apo2L resistance,” Dr. Frans van Valen and colleagues from University Hospital in M?nster explain in the December 20 issue of The International Journal of Cancer. They studied the effects of recombinant TRAIL/Apo2L in combination with a variety of cancer drugs on human osteosarcoma and Ewing’s tumor cells and on normal human synovial cells, fibroblasts and osteoblasts. All of the tumor cell lines were resistant to apoptosis induction by TRAIL/Apo2L, consistent with what is known about this naturally occurring apoptosis ligand. The TRAIL/Apo2L-etoposide combination sensitized and killed cultured bone tumor cells and spared normal healthy cells. Combining TRAIL/Apo2L and other drugs commonly used in bone cancer – including doxorubicin and actinomycin – sensitized both tumor cells and normal cells to TRAIL/Apo2L-induced apoptosis. The combination of TRAIL/Apo2L and etoposide, which selectively kills tumor cells, “may provide a new therapeutic modality for bone tumour,” Dr. van Valen told Reuters Health. (Source: Int J Cancer 2003;107:929-940: Reuters Health: Megan Rauscher: December 31, 2003: Oncolink)