Cytotoxicity and structure activity relationship studies of maplexins A-I, gallotannins from red maple (Acer rubrum)

Maplexins A-I are a series of structurally related gallotannins recently isolated from the red maple (Acer rubrum) species. They differ in number and location of galloyl derivatives attached to 1,5-anhydro-glucitol. Here, maplexins A-I were evaluated for anticancer effects against human tumorigenic (colon, HCT-116; breast, MCF-7) and non-tumorigenic (colon, CCD-18Co) cell lines. The maplexins which contained two (maplexins C-D) or three (maplexins E-I) galloyl derivatives each, inhibited cancer cell growth while those with only one galloyl group (maplexins A-B) did not. Moreover, maplexins C-D showed greater antiproliferative effects than maplexins E-I (IC50 = 59.8-67.9 and 95.5-108.5 μM vs. 73.7-165.2 and 115.5-182.5 μM against HCT-116 and MCF-7 cells, respectively). Notably, the cancer cells were up to 2.5-fold more sensitive to the maplexins than the normal cells. In further mechanistic studies, maplexins C-D (at 75 μM concentrations) induced apoptosis and arrested cell cycle (in the S-phase) of the cancer cells. These results suggest that the number of galloyl groups attached to the 1,5-anhydro-glucitol moiety in these gallotannins are important for antiproliferative activity. Also, this is the first in vitro anticancer study of maplexins.

► Maplexins A-I are new gallotannins previously isolated from the red maple species. ► Maplexins showed cytotoxic effects against human cancer cells to a greater effect than normal cells. ► Antiproliferative effects of maplexins were mediated through cell cycle arrest and apoptosis. ► SAR studies revealed that two galloyl groups on 1,5-anhydro-glucitol is important for anticancer effects.