Identification and Characterization of the Caspase-Mediated Apoptotic Activity of and an Isolated Compound in Human Cancer Cells.

Plants of the genus (Lamiaceae or Labiatae family) are known historically for their medicinal value. Here, we identify and characterize the anticancer potential of and its active compound, IM60, in human cancer cells. The anti-proliferative effect of a methanol extract and its various fractions were analyzed in MCF-7 and HeLa cells in a dose- and time dependent manner. The dichloromethane fraction (TMDF) was observed to be the most effective with cytotoxicity against a more expanded series of cell lines, including MDA-MB-231. A time and dose-dependent toxicity profile was also observed for IM60; it could induce rapid cell death (within 3 h) in MCF-7 cells. Activation of caspases and PARP, hallmarks of apoptotic cell death pathways, following treatment with TMDF was demonstrated using western blot analysis. Inversion of the phosphatidylserine phospholipid from the inner to the outer membrane was confirmed by annexin V staining that was inhibited by the classical apoptosis inhibitor, Z-VAK-FMK. Changes in cell rounding, shrinkage, and detachment from other cells following treatment with TMDF and IM60 also supported these findings. Finally, the potential of TMDF and IM60 to induce enzymatic activity of caspases was also demonstrated in MCF-7 cells. This study, thus, not only characterizes the anticancer potential of , but also identifies a lead terpenoid, IM60, with the potential to activate anticancer cell death pathways in human cancer cells.