| Title: |
Inhibitory effect of blestriarene C on triple-negative breast cancer: Inducing ferroptosis and mitophagy via SESN2/AKT/FOXO4 axis |
| Authors: |
An, Junsha; Chen, Pingting; Han, Mingyu; Zhang, Heng; Lu, Yajie; Tang, Hailin; Bi, Qian; Pan, Weiwei; Peng, Cheng; Zhou, Zhaokai; Peng, Fu |
| Source: |
Chinese Medical Journal ; volume 139, issue 5, page 699-709 ; ISSN 0366-6999 2542-5641 |
| Publisher Information: |
Ovid Technologies (Wolters Kluwer Health) |
| Publication Year: |
2026 |
| Description: |
Background: Triple-negative breast cancer (TNBC) is a highly aggressive and treatment-resistant subtype of breast cancer, characterized by high rates of metastasis and mortality. This study aimed to identify and evaluate the therapeutic potential of blestriarene C (BC), a novel diphenanthrene compound, in the treatment of TNBC. The study also sought to explore the underlying mechanisms and signaling pathways involved in BC’s antitumor effects. Methods: A multiomics analysis was conducted to identify key genes and pathways involved in TNBC treatment. We performed experiments related to cell viability, ferroptosis, and mitophagy to explore the effects of BC in the treatment of TNBC, utilizing the TNBC cell lines BT-549 and 4T1 cells. The impact of sestrin 2 (SESN2) knockout on BC’s effects was also studied. We also conducted in vivo experiments using the patient-derived xenograft (PDX) model in zebrafish to assess the antitumor effects of BC. Results: The results of RNA sequencing and proteomics showed that ferroptosis and mitophagy may be the main mechanisms of BC acting on TNBC cells. BC could inhibit cell proliferation by modulating the phosphoinositide 3-kinase/protein kinase B/forkhead box O4 and SESN2/mechanistic target of rapamycin signaling pathways, and inducing ferroptosis and mitophagy. SESN2 and microtubule-associated protein 1 light chain 3 beta (MAP1LC3B), as hub genes, participated in regulating the therapeutic effect of BC on TNBC. TNBC tumors in zebrafish treated with BC were smaller and lighter, indicating that BC had antitumor effect. Conclusions: BC emerges as a promising therapeutic agent for TNBC by targeting SESN2 and MAP1LC3B, modulating associated signaling pathways, and inducing ferroptosis and mitophagy. These findings provide the basis for further investigation of BC’s potential as a targeted therapy for TNBC. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1097/cm9.0000000000003960 |
| DOI: |
10.1097/CM9.0000000000003960 |
| Availability: |
https://doi.org/10.1097/cm9.0000000000003960; https://journals.lww.com/10.1097/CM9.0000000000003960 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.90C8A831 |
| Database: |
BASE |