| Summary: | An n-hexane extract of <i>Callistemon subulatus</i> was found to exhibit potent cytotoxicity against PANC-1 human pancreatic cancer cells, preferentially under nutrition starvation conditions, with a PC<sub>50</sub> value of 6.2 µg/mL. Phytochemical investigation of this bioactive extract resulted in the isolation of fifteen compounds (<b>1</b>–<b>15</b>), including a new compound, subulatone A (–). The structure of compound <b>1</b> 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 (<b>2</b>) showed highly potent preferential cytotoxicity, with a PC<sub>50</sub> value of 0.28 µM. Myrtucommulone A (<b>2</b>) 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 (<b>2</b>) is a lead compound for anticancer drug development based on an anti-austerity strategy.
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