Andrographolide induced ferroptosis in multiple myeloma cells by regulating the P38/Nrf2/HO-1 pathway

• Published in: Archives of biochemistry and biophysics Vol. 742; p. 109622
• Main Authors: Li, Wenxia, Fu, Hangjie, Fang, Liuyuan, Chai, Hui, Ding, Bin, Qian, Shenxian
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2023
• Subjects: Andrographolide; Diterpenes - pharmacology; Ferroptosis; Humans; Multiple myeloma; Multiple Myeloma - drug therapy; NF-E2-Related Factor 2 - metabolism; Nrf2/HO-1 signaling pathway; P38 MAPK; P38 MAPK; Ferroptosis; Nrf2/HO-1 signaling pathway; Andrographolide; Multiple myeloma
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2023.109622

Andrographis paniculata is used as a functional food in Asia. Andrographolide (Andro), a diterpene lactone isolated from Andrographis paniculata, has been reported to have potent anticancer activity. Multiple myeloma (MM), the second most common malignant tumor in hematology, is incurable. Ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation, has shown potential in the treatment of various cancers. However, previous studies have not demonstrated whether Andro inhibits the development of MM via ferroptosis or any other mechanism. In the present study, we observed that Andro induced cell death, G0/G1 cell cycle arrest and evoked oxidative stress in MM cells. Interestingly, these phenomena were accompanied by increases in intracellular and mitochondrial Fe2+ and lipid peroxidation levels. Furthermore, treatment with ferroptosis inhibitors rescued Andro-induced cell death, which indicated that ferroptosis contributed to this phenomenon. Mechanistic examination showed that Andro may block the Nrf2/HO-1 signaling pathway by activating P38, thereby inducing ferroptosis. Moreover, inhibition of P38 expression rescued Andro-induced cell death, changes in the level of Nrf2 and HO-1 expression, Fe2+ and lipid peroxidation. Taken together, our findings suggest that Andro induces ferroptosis in MM cells via the P38/Nrf2/HO-1 pathway, providing a potential preventative and therapeutic approach for MM. [Display omitted] •Andrographolide has anti-multiple myeloma effect.•Andrographolide functions as a ferroptosis inducer in multiple myeloma.•Andrographolide induce multiple myeloma through P38-Nrf2-HO1 pathway.