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Novel methyltransferase G9a inhibitor induces ferroptosis in multiple myeloma through Nrf2/HO-1 pathway.
Zhang, Yu; Wang, Xiaoshun; Li, Xiaoqi; Xiong, Xingfang; Xue, Renyu; Zang, Lanlan; Wang, Zhiqiang; Wang, Lijuan.
Afiliação
  • Zhang Y; Postgraduate Training Base of Linyi People's Hospital, Guangzhou University of Chinese Medicine, Linyi, China.
  • Wang X; Central Laboratory, Linyi People's Hospital, Linyi, China.
  • Li X; Qingdao Municipal Hospital, Qingdao, China.
  • Xiong X; Central Laboratory, Linyi People's Hospital, Linyi, China.
  • Xue R; School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China.
  • Zang L; Postgraduate Training Base of Linyi People's Hospital, Guangzhou University of Chinese Medicine, Linyi, China.
  • Wang Z; Central Laboratory, Linyi People's Hospital, Linyi, China.
  • Wang L; Central Laboratory, Linyi People's Hospital, Linyi, China.
Ann Hematol ; 103(7): 2405-2417, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38538975
ABSTRACT
Multiple myeloma (MM) is a common malignant hematologic neoplasm, and the involvement of epigenetic modifications in its development and drug resistance has received widespread attention. Ferroptosis, a new ferroptosis-dependent programmed death mode, is closely associated with the development of MM. The novel methyltransferase inhibitor DCG066 has higher cell activity, but its mechanism of action in MM has not been clarified. Here, we found that DCG066 (5µM) inhibited the proliferation and induced ferroptosis in MM cells; the intracellular levels of ROS, iron, and MDA were significantly elevated, and the level of GSH was reduced after the treatment of DCG066; The protein expression levels of SLC7A11, GPX4, Nrf2 and HO-1 were significantly reduced, and these phenomena could be reversed by ferroptosis inhibitor Ferrostatin-1 (Fer-1) and Nrf2 activator Tert-butyl hydroquinone (TBHQ). Meanwhile, the protein expression levels of Keap1 was increased, and heat shock proteins (HSP70, HSP90 and HSPB1) were reduced after DCG066 treatment. In conclusion, this study confirmed that DCG066 inhibits MM proliferation and induces ferroptosis via the Nrf2/HO-1 pathway.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Heme Oxigenase-1 / Fator 2 Relacionado a NF-E2 / Ferroptose / Mieloma Múltiplo Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Heme Oxigenase-1 / Fator 2 Relacionado a NF-E2 / Ferroptose / Mieloma Múltiplo Idioma: En Ano de publicação: 2024 Tipo de documento: Article