Cytotoxic Nitrobenzoyl Sesquiterpenoids from an Antarctica Sponge-Derived <i>Aspergillus insulicola</i>
Chunxiao Sun, Xiaoyu Liu, Ning Sun, Xiaomin Zhang, Mudassir Shah, Guojian Zhang, Qian Che, Tianjiao Zhu, Jing Li, Dehai Li
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive neoplastic diseases of the pancreas with fatal proliferation and metastasis and no medicine available for treatment. From an Antarctica sponge-derived fungus, Aspergillus insulicola HDN151418, four new nitrobenzoyl sesquiterpenoids, namely, insulicolides D–G (1–4), were isolated. Compounds 3 and 4 exhibited selective inhibition against human PDAC cell lines. Further studies indicated that compound 4 could significantly suppress cell proliferation to induce apoptosis and blocked migration and invasion of PDAC cells. Compound 4 could also avoid resistance and improved the therapeutic effect of the chemotherapy drug gemcitabine. A preliminary mechanism study showed that compound 4 can significantly inhibit the expression of EGFR and XIAP in PDAC cells. Altogether, 4 is a potential lead compound for anti-PDAC drug research.