Sugiol (127horbar;hydroxyabieta-8,11,13-trien-7-one) targets human pancreatic carcinoma cells (Mia-PaCa2) by inducing apoptosis, G2/M cell cycle arrest, ROS production and inhibition of cancer cell migration.

PURPOSE: Plants produce a diversity of molecular scaffolds with tremendous pharmacological potential. In the present study we evaluated the anticancer activity of the plant-derived natural product sugiol. We also evaluated its effects on apoptosis-related key proteins, cell cycle phase distribution, reactive oxygen species (ROS) and mitochondrial membrane potential (MMP).

METHODS: Cell viability was evaluated by MTT assay while clonogenic assay was done to determine the effects of sugiol on the cancer cell colony formation. Flow cytometric measurements were carried out in order to assess the effects of sugiol on cell cycle progression, apoptosis, MMP and ROS generation.

RESULTS: Sugiol reduced the cell viability of Mia-PaCa2 human pancreatic cancer cells in a concentration-dependent manner. The IC50 of sugiol on the cell line was 15 μM. The anticancer activity of sugiol was found to be ROS-mediated alterations in MMP, ultimately favoring apoptosis as determined by the annexin V/propidium iodide (PI). Additionally, sugiol caused cell cycle arrest in G2/M phase of the cell cycle and upregulated the expression of Bax, with concomitant downregulation of Bcl-2 expression in comparison to the untreated cells. It also inhibited the migratory capacity of Mia-PaCa2 cells at the IC50 concentration.

CONCLUSION: In conclusion our results indicate that sugiol is a potent anticancer molecule and may prove essential in pancreatic cancer therapy.