Benzophenones from <i>Betula alnoides</i> with Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Cell Line

Abstract

The antiausterity strategy is a promising approach for the discovery of lead compounds with unprecedented anticancer activities by targeting the tolerance of cancer cells to nutrition starvation. These agents are selectively cytotoxic under the tumor microenvironment-mimicking condition of nutrition starvation, without apparent toxicity in the normal nutrient-rich condition. In this study, an ethanol extract of <i>Betula alnoides</i> showed antiausterity activity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC₅₀ value of 13.2 μg/mL. Phytochemical investigation of this active extract led to the isolation of eight benzophenones (<b>1</b>-<b>8</b>), including six new compounds, named betuphenones A-F (<b>2</b>-<b>7</b>), and three known xanthones (<b>9</b>-<b>11</b>). The structure elucidation of the new compounds was achieved by HRFABMS, NMR, and ECD spectroscopic analyses. A plausible biogenetic pathway of the new compounds was proposed. Compounds <b>1</b>-<b>7</b> displayed antiausterity activity with PC₅₀ values of 4.9-8.4 μM. Moreover, compounds <b>2</b> and <b>7</b> induced alterations in PANC-1 cell morphology under nutrient-deprived conditions and also inhibited PANC-1 colony formation under nutrient-rich conditions.