Cell Toxicity Studies of Tremetone Isolated From Rayless Goldenrod (Isocoma pluriflora)

Abstract

This research compared the cytotoxic actions of the benzofuran ketone tremetone in B16 murine melanoma cells, TE‐671 human rhabdomyosarcoma cells, and SH‐SY5Y human neuroblastoma cells using a MTT assay, with and without exposure to rat liver microsomes (RLM). Tremetone is of interest because it is a putative toxin in white snakeroot and rayless goldenrod. Identifying the toxic principal(s) of white snakeroot is important because in addition to poisoning livestock by causing “trembles,” it also causes “milk sickness” in humans that drink the milk from dairy animals that have eaten these toxic plants. Tremetone was not cytotoxic in B16 cells. In TE‐671 and SH‐SY5Y cells, concentration‐dependent tremetone cytotoxicity occurred without microsomal activation. In SH‐SY5Y cells the best fit values were; tremetone IC50 = 490 μM, tremetone and RLM IC50 = 505 μM. In TE‐671 cells the best fit values were; tremetone IC50 = 2.5 μM, tremetone and RLM IC50 = 2.2 μM. These results suggest that in B16 cells, tremetone is not cytotoxic. The results from experiments with SH‐SY5Y and TE‐671 cells suggest that tremetone does not require microsomal activation to be cytotoxic in a concentration‐dependent manner. This study demonstrates that tremetone is cytotoxic and plays a role in the disease caused by white snakeroot and rayless goldenrod.Support or Funding InformationThis research was supported by USDA.