Synergy of Pancratistatin and Tamoxifen in inducing apoptosis in breast cancer cells.

摘要

The development of chemotherapeutics for cancer has as its holy-grail, targeted reagents and better still, synergistic combinations of such selective reagents. Breast cancer has at least two widely used targeted therapies: the anti-epidermal growth factor receptor monoclonal antibody Herceptin for HER-2 positive cancers and the anti-estrogen tamoxifen for estrogen receptor positive tumors.In a series of publications over the past three years Dr. Pandey's group at the Univ of Windsor in collaboration with Dr. McNulty at McMaster have shown that pancratistatin, an alkaloid derived from the Hawaiian spider lily (fam. amaryllidaceae) induces apoptosis selectively in several cancer cell lines while sparing cognate normal cell lines by selectively targeting the mitochondria.In this issue of Cancer Biology & Therapy, Siedalowski et al. have demonstrated the synergy between tamoxifen and pancratistatin, on both estrogen receptor positive and negative human breast cancer cell lines in vitro. The authors claim that pancratistatin disrupts the mitochondrial membrane potential leading to apoptosis specifically in breast cancer cells with minimal toxicity to normal mammary cell lines. Cancer cells treated with pancratistatin and tamoxifen experienced destabilization of the mitochondrial membrane, leading to increased production of reactive oxygen species. They propose