Chemical Constituents of Callistemon subulatus and Their Anti-Pancreatic Cancer Activity against Human PANC-1 Cell Line.

An n-hexane extract of Callistemon subulatus was found to exhibit potent cytotoxicity against PANC-1 human pancreatic cancer cells, preferentially under nutrition starvation conditions, with a PC 50 value of 6.2 µg/mL. Phytochemical investigation of this bioactive extract resulted in the isolation of fifteen compounds ( 1 - 15 ), including a new compound, subulatone A (-). The structure of compound 1 was elucidated using HRFABMS and NMR spectroscopic analyses. The isolated compounds were tested for their preferential cytotoxicity against the PANC-1 human pancreatic cancer cell line, using an anti-austerity strategy. Among these, myrtucommulone A ( 2 ) showed highly potent preferential cytotoxicity, with a PC 50 value of 0.28 µM. Myrtucommulone A ( 2 ) was found to alter PANC-1 cell morphology, inhibit cell migration, and downregulate the PI3K/Akt/mTOR and autophagy signaling pathways in nutrient-deprived media, leading to cancer cell death. Therefore, myrtucommulone A ( 2 ) is a lead compound for anticancer drug development based on an anti-austerity strategy.