Four previously undescribed heterodimeric diketopiperazine alkaloids, expansines A-D, were identified from the solid rice medium fermented by Penicillium expansum MA147, along with one new resorcylic acid derivative and five known compounds. Their structures and relative/absolute configurations were elucidated by interpretation of their spectroscopic data, quantum chemical calculations, and chemical conversion. Some obtained compounds were evaluated for the cytotoxicity against a triple-negative breast cancer cell line MDA-MB-231, and expansine C showed an IC50 value of 3.23 mu M. In further mechanistic studies, we found that it might act by increasing the expression of ATP-binding cassette transporter A1 and reducing cellular cholesterol levels, suggesting its potential as a novel anti-cancer agent.