Bo Yuan
Tokyo University, Japan
Title: Cytocidal effects of active bufadienolides on human cancer cells and its possibility of enhancing host immunity as an adjuvant therapeutic reagent
Biography
Biography: Bo Yuan
Abstract
The growth inhibitory effects of bufadienolide compounds were investigated in a human glioblastoma cell line U-87 and a pancreatic cancer cell line SW1990. Among four bufadienolide compounds, a dose-dependent cytotoxicity was observed in these cancer cells after treatment with gamabufotalin and arenobufagin. The IC50 values of the two compounds were 3-5 times higher in normal peripheral blood mononuclear cells (PBMCs) than those in both cancer cells. However, similar phenomena were not observed in other two bufadienolide compounds, telocinobufagin and bufalin. These results thus suggested that gamabufotalin and arenobufagin possessed a selective cytotoxic activity against tumor cells rather than normal cells. Moreover, a clear dose-dependent lactate dehydrogenase (LDH) release, a well-known hallmark of necrosis, was observed in both cancer cells treated with gamabufotalin, suggesting that gamabufotalin-mediated cell death is predominantly associated with a necrosis-like phenotype. Of most importance, treatment with as little as 8 ng/ ml of gamabufotalin, even an almost nontoxic concentration to PBMCs, efficiently downregulated the percentages of CD4+CD25+Foxp3+ regulator T (Treg) cells in mitogen-activated PBMCs. Given that Treg cells play a critical role in tumor immunotolerance by suppressing the antitumor immunity, these results suggested that gamabufotalin could be served as a promising candidate of adjuvant therapeutic reagent by manipulating Treg cells to enhance the efficacy of conventional anticancer drugs and less their side effects. These findings provide insights into the clinical application of gamabufotalin for cancer patients with glioblastoma/pancreatic cancer based on its cytocidal effect against tumor cells as well as depletion of Treg cells.