Naphthoquinone-derived ZSW-4B induces apoptosis in triple-negative breast cancer via AMPK signalling activation

Triple-negative breast cancer (TNBC) is the most malignant molecular subtype of breast cancer and is characterized by aggressiveness, high mortality, significant heterogeneity, and poor prognosis. AMPK plays a critical role in maintaining the cellular energy balance, and its inactivation is associated with malignant breast cancer. Here, we identified the pharmacological mechanism of the 1,4-naphthoquinone derivative ZSW-4B. MTT, colony formation, and nude mouse xenograft tumour models demonstrated that ZSW-4B selectively inhibits the proliferation of TNBC cells both in vitro and in vivo. Flow cytometry and Western blot analysis revealed that ZSW-4B induces apoptosis in TNBC cells. Phosphoproteomic analysis revealed activation of the AMPK signalling pathway by ZSW-4B. Additionally, the application of the CRISPR-Cas9 system to genetically knockout AMPK in TNBC cell lines was demonstrated to reverse the antitumour effects elicited by ZSW-4B both in vitro and in vivo. In summary, ZSW-4B inhibits TNBC by inducing cellular apoptosis through the activation of AMPK.

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Publication Details

Journal
Scientific Reports
Published
2024-11-18
DOI
https://doi.org/10.1038/s41598-024-79592-9
Primary Topic
Bioactive Compounds and Antitumor Agents
Type
article
Field-Weighted Citation Impact
0.00

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article

Naphthoquinone-derived ZSW-4B induces apoptosis in triple-negative breast cancer via AMPK signalling activation

Yuanzhu Xie, Shuaiwen Zhu, Xiyuan Hu, Zhiyong Luo et al.
Scientific Reports
Bioactive Compounds and Antitumor Agents
article

Naphthoquinone-derived ZSW-4B induces apoptosis in triple-negative breast cancer via AMPK signalling activation

Yuanzhu Xie, Shuaiwen Zhu, Xiyuan Hu, Zhiyong Luo, Tiao Luo, Min Wen, Zizheng Zou, Ling Chen, Xiaohe Liu, Hongdou Liu, Qunfang Xu, Suyou Liu, Wensong Luo, Mo Li, Ting Peng, Liu Mingquan
article en

Abstract

Triple-negative breast cancer (TNBC) is the most malignant molecular subtype of breast cancer and is characterized by aggressiveness, high mortality, significant heterogeneity, and poor prognosis. AMPK plays a critical role in maintaining the cellular energy balance, and its inactivation is associated with malignant breast cancer. Here, we identified the pharmacological mechanism of the 1,4-naphthoquinone derivative ZSW-4B. MTT, colony formation, and nude mouse xenograft tumour models demonstrated that ZSW-4B selectively inhibits the proliferation of TNBC cells both in vitro and in vivo. Flow cytometry and Western blot analysis revealed that ZSW-4B induces apoptosis in TNBC cells. Phosphoproteomic analysis revealed activation of the AMPK signalling pathway by ZSW-4B. Additionally, the application of the CRISPR-Cas9 system to genetically knockout AMPK in TNBC cell lines was demonstrated to reverse the antitumour effects elicited by ZSW-4B both in vitro and in vivo. In summary, ZSW-4B inhibits TNBC by inducing cellular apoptosis through the activation of AMPK.

Scientific ReportsVol. 14(1)
Central South University (CN), Xinjiang Medical University (CN)
National Natural Science Foundation of China, China Postdoctoral Science Foundation, Natural Science Foundation of Hainan Province, Kunming Institute of Zoology, Chinese Academy of Sciences
Good health and well-being
Openalex Percentile: Top 79%
Bioactive Compounds and Antitumor Agents
DOIOpen Access PDFOpenAlex
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