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  2. Sodium molybdate inhibits the growth of ovarian cancer cells via inducing both ferroptosis and apoptosis

Sodium molybdate inhibits the growth of ovarian cancer cells via inducing both ferroptosis and apoptosis

  • Free Radic Biol Med. 2022 Mar;182:79-92. doi: 10.1016/j.freeradbiomed.2022.02.023.
Guoping Mao 1 Dedong Xin 2 Qian Wang 3 Dongmei Lai 4
Affiliations

Affiliations

  • 1 International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, PR China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, PR China.
  • 2 College of Chemistry and Life Science, Zhejiang Normal University, Jinhua, 321004, PR China.
  • 3 International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, PR China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, PR China. Electronic address: paulia@163.com.
  • 4 International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, PR China; Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, PR China. Electronic address: laidongmei@hotmail.com.
Abstract

Ovarian Cancer has the most mortality of all gynecologic malignancies. High-grade serous ovarian carcinoma (HGSOC) is the most common and deadly type of ovarian Cancer. Tumor recurrence occurs due to the emergence of chemotherapy resistance. Thus, searching for new therapeutic strategies is essential for the management of ovarian Cancer. Deregulation of iron metabolism can be used by ovarian Cancer cells to survive, proliferate and metastasize. Here we report that sodium molybdate, a soluble molybdenum (Mo) compound, induces the elevation of the labile iron pool (LIP) in ovarian Cancer cells, correlated with the down-regulation of genes involved in extracellular matrix organization. Sodium molybdate also induces depletion of glutathione (GSH) through mediating the production of nitric oxide (NO). Elevation of LIP and depletion of GSH promote the Ferroptosis of ovarian Cancer cells. Meanwhile, nitric oxide induces mitochondrial damage through inhibiting mitochondrial aconitase activity, ATP production, and mitochondrial membrane potential, leading to Apoptosis of ovarian Cancer cells. In vivo study shows that sodium molybdate reduces tumor burden in nude mice. Xenografts treated with sodium molybdate are characterized by obvious iron accumulation, increased expression of the iron storage protein ferritin, and lipid peroxide product 4-hydroxynonenal. In addition, an elevated percentage of apoptotic cells is observed in xenografts treated with sodium molybdate. Taken together, these results demonstrate that sodium molybdate can induce both Ferroptosis and Apoptosis of ovarian Cancer cells, making it a potential therapeutic candidate for ovarian Cancer.

Keywords

Apoptosis; Chemoresistance; Ferroptosis; Ovarian cancer; Sodium molybdate.

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