Abietane diterpenes from Abies spectabilis and their anti-pancreatic cancer activity against the MIA PaCa-2 cell line

An ethanolic extract of the stem of Abies spectabilis exhibited strong cytotoxicity against MIA PaCa-2 human pancreatic cancer cells preferentially under nutrient-deprived conditions. Therefore, phytochemical investigation of this bioactive extract was carried out, and that led the isolation of ten compounds (1–10) including a new abietane-type diterpene (1). The structure of the new compound (1) was elucidated by combined spectroscopic techniques, including HRFABMS, NMR and quantum ECD calculation. All the isolated compounds were evaluated for their efficacy against MIA PaCa-2 human pancreatic cancer cell line by employing an anti-austerity strategy. Among the tested compounds, dehydroabietinol (5) displayed the most potent activity with a PC₅₀ value of 6.6 μM. Dehydroabietinol (5) was also found to retard the MIA PaCa-2 cell migration under normal nutrient-rich conditions displaying its anti-metastatic potential. Investigation on the mechanism suggested that dehydroabietinol (5) is an inhibitor of the key cancer cell survival Akt/mTOR/autophagy signaling pathway.