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A novel methuosis inducer DZ-514 possesses antitumor activity via activation of ROS-MKK4-p38 axis in triple negative breast cancer.
Wang, Luzhen; Mi, Dazhao; Hu, Jinhui; Liu, Wenjing; Zhang, Yi; Wang, Chunyan; Chen, Yihua; Chen, Ceshi.
Afiliación
  • Wang L; School of Life Science, University of Science & Technology of China, Hefei, 230027, Anhui, China; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China
  • Mi D; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
  • Hu J; The First Hospital of Hunan University of Chinese Medicine, Changsha, 410007, Hunan, China.
  • Liu W; The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118, China.
  • Zhang Y; Department of Breast and Thyroid Surgery, Southwest Hospital, The First Affiliated Hospital of the Army Military Medical University, Chongqing, 400038, China.
  • Wang C; Department of the Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China. Electronic address: chunyan740729@sina.com.
  • Chen Y; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. Electronic address: yhchen@bio.ecnu.edu.cn.
  • Chen C; Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650201, China; The Third Affiliated Hospital, Kunming Medical University, Kunming, 650118, China; Academy of Biomed
Cancer Lett ; 555: 216049, 2023 02 28.
Article en En | MEDLINE | ID: mdl-36608865
Triple-negative breast cancer (TNBC) is one of the most malignant tumors with poor prognosis. Methuosis is a new type of nonapoptotic cell death characterized by the accumulation of cytoplasmic vacuoles. In this study, we synthesized and screened a series of N-phenyl-4-pyrimidinediamine derivatives in TNBC cells, finding that DZ-514 was the best compound with high toxicity independent of the inhibition of BCL6. DZ-514 decreased cell viability, inhibited cell cycle progression, and induced caspase-independent cell death in TNBC cells. Interestingly, DZ-514 induced cytoplasm vacuolation, which could be blocked by Baf A1, the V-ATPase inhibitor. Furthermore, we found that DZ-514-induced vacuoles were derived from macropinosomes rather than autophagosomes. Most importantly, methuosis induced by DZ-514 was partially mediated by activating the ROS-MKK4-p38 axis. Finally, we demonstrated that DZ-514 significantly inhibited tumor growth in an HCC1806 xenograft mouse model. These findings revealed that the novel methuosis inducer DZ-514 could be developed for TNBC treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Lett Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cancer Lett Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Irlanda