Nitrobenzoyl-insulicolide A: a novel dinitrobenzoyl sesquiterpenoid, induces autophagic cell death in small cell lung cancer cells.

Authors

Yige Zhang, Xiaomin Zhang, Chunxiao Sun, Xin Qi, Dehai Li, Jing Li

Published in

Marine life science & technology. Volume 7. Issue 4. Pages 949-961. Epub May 12, 2025.

Abstract

Small cell lung cancer (SCLC) is a high-grade malignancy and prone to drug resistance, with limited progress in patient survival over the past 30 years. Therefore, there is an urgent need to explore new treatment strategies for SCLC patients. Autophagic cell death represents a novel therapeutic strategy for cancer cells with high apoptotic thresholds. Here, we demonstrate that nitrobenzoyl-insulicolide A (1), a new sesquiterpene, isolated from Antarctica sponge-derived fungus Aspergillus insulicola HDN151418, inhibits the proliferation of various SCLC cells including adriamycin- or cisplatin/etoposide-resistant cells, via autophagic death rather than apoptosis, necrosis and cell aging. Molecular mechanism analysis revealed that compound 1 induced autophagic cell death in the NCI-H446 and H69 AR cells dependent on activations of the AKT/mTOR/PARP and ERK1/2 signaling pathways. These findings provide an experimental basis for the further development of 1 as a lead compound against small cell lung cancer in future.
The online version contains supplementary material available at 10.1007/s42995-025-00292-y.

PMID:
41322261
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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