Anomanolide C suppresses tumor progression and metastasis by ubiquitinating GPX4-driven autophagy-dependent ferroptosis in triple negative breast cancer

Anomanolide C (AC), a natural withanolide isolated from , has been reported to have exhibits remarkable anti-tumour activities in several types of human cancers, particularly triple-negative breast cancer (TNBC). However, its intricate mechanisms still remain need to be clarified. Here, we evaluated...

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Bibliographic Details
Published in:	International journal of biological sciences Vol. 19; no. 8; pp. 2531 - 2550
Main Authors:	Chen, Yan-Mei, Xu, Wei, Liu, Yang, Zhang, Jia-Hui, Yang, Yuan-Yuan, Wang, Zhi-Wen, Sun, De-Juan, Li, Hua, Liu, Bo, Chen, Li-Xia
Format:	Journal Article
Language:	English
Published:	Australia Ivyspring International Publisher Pty Ltd 01-01-2023 Ivyspring International Publisher
Subjects:	Antibodies Anticancer properties Apoptosis Autophagy Breast cancer Cancer therapies Cell culture Cell Line, Tumor Cell Proliferation Chemotherapy Drug development Ferroptosis Humans Metastases Metastasis Oxidative stress Proteins Research Paper Triple Negative Breast Neoplasms - metabolism Tumors Ubiquitination United States > US China Ferroptosis Ubiquitination GPX4 Anomanolide C Autophagy Triple negative breast cancer
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Summary:	Anomanolide C (AC), a natural withanolide isolated from , has been reported to have exhibits remarkable anti-tumour activities in several types of human cancers, particularly triple-negative breast cancer (TNBC). However, its intricate mechanisms still remain need to be clarified. Here, we evaluated whether AC could inhibit cell proliferation and the role of AC in ferroptosis induction and autophagy activation. Subsequently, the anti-migration potential of AC was found via autophagy-dependent ferroptosis Additionally, we found that AC reduced the expression of GPX4 by ubiquitination and inhibited TNBC proliferation and metastasis and Moreover, we demonstrated that AC induced autophagy-dependent ferroptosis, and led to Fe accumulation ubiquitinating GPX4. Moreover, AC was shown to induce autophagy-dependent ferroptosis as well as to inhibit TNBC proliferation and migration GPX4 ubiquitination. Together, these results demonstrated that AC inhibited the progression and metastasis of TNBC by inducing autophagy-dependent ferroptosis ubiquitinating GPX4, which might shed light on exploiting AC as a new drug candidate for the future TNBC therapy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. Competing Interests: The authors have declared that no competing interest exists.
ISSN:	1449-2288 1449-2288
DOI:	10.7150/ijbs.82120