Imperatorin shows selective antitumor effects in SGC-7901 human gastric adenocarcinoma cells by inducing apoptosis, cell cycle arrest and targeting PI3K/Akt/m-TOR signalling pathway

Purpose: The main purpose of the present study was to determine the anticancer properties of imperatorin - a naturally occurring coumarin compound-against SGC-7901 human gastric adenocarcinoma cells and the mouse fibroblast cell line 3T3 (normal cell line). Methods: Imperatorin effects on apoptosis induction, cell cycle phase distribution and PI3K/Akt/m-TOR signalling pathways were studied. MTT cell viability assay examined the compound's cytotoxic potential, while inverted phase contrast microscopy and fluorescence microscopy techniques were used to study morphological changes induced in SGC-7901 cells by imperatorin. Flow cytometry examined its effects on cell cycle progression while Western blot assay was used to study changes in protein expressions of PI3K/Akt/m-TOR pathway. Results: Imperatorin induced a dose-dependent growth inhibition of the SGC-7901 gastric cancer cells with an IC50 value 62.6 mu M, while in case of normal 3T3 mouse fibroblast cells, the drug did not show significant toxicity (IC50 value 195.8 mu M), indicating that the drug selectively induced cytotoxicity in gastric cancer cells. The cells became rounded up, shrunken in size and got detached from the monolayer attached to well surface. Cells treated with 10, 75 and 175 mu M imperatorin indicated that they began to emit yellow or red fluorescence which is an indication of early or late apoptosis respectively. Imperatorin also induced significant DNA fragmentation along with increasing the fraction of sub-G1 cells, indicating a sub-G1 cell cycle arrest. Conclusion: Imperatorin could prove an important lead molecule for the treatment of gastric cancer and deserves further research in vivo against more cell lines.