Citation: Dachuan Qi, Lei Xing, Lijun Shen, Wenshuang Sun, Cheng Cai, Chunhua Xue, Xuwei Song, Hua Yu, Hulin Jiang, Chengjun Li, Qingri Jin, Zhiqi Zhang. A GSH-depleted platinum(Ⅳ) prodrug triggers ferroptotic cell death in breast cancer[J]. Chinese Chemical Letters, ;2022, 33(10): 4595-4599. doi: 10.1016/j.cclet.2022.03.105 shu

A GSH-depleted platinum(Ⅳ) prodrug triggers ferroptotic cell death in breast cancer

Dachuan Qi ^{a, 1} ,
Lei Xing ^{b, 1} ,
Lijun Shen ^{b, 1} ,
Wenshuang Sun ^{d, 1} ,
Cheng Cai ^a ,
Chunhua Xue ^a ,
Xuwei Song ^a ,
Hua Yu ^a ,
Hulin Jiang ^{b, *,} ,
Chengjun Li ^{d, *,} ,
Qingri Jin ^{c, *,} ,
Zhiqi Zhang ^{a, *,}

a.
Department of General Surgery, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China
b.
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China
c.
Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A & F University, Lin'an 311300, China
d.
Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China

jianghulin3@gmail.com

Received Date: 1 September 2021
Revised Date: 28 March 2022
Accepted Date: 29 March 2022
Available Online: 4 April 2022

Figures(3)

Cisplatin is the first-line drug for treatment of various solid tumors including breast cancer due to the broad anti-tumor spectrum and strong anti-tumor effect. However, serious side effects and long-term medication of reduced sensitivity by high GSH in tumor cells have severely restricted its further clinical application. Herein, a GSH-depleted Pt(Ⅳ) prodrug (Platin B) based on cisplatin and 4-carboxylphenylboronic acid pinacol ester was prepared to solve the problems. As an excellent GSH scavenger, 4-carboxylphenylboronic acid pinacol ester could be activated by intracellular redox reactions to release quinone methide, thereby amplifying oxidative stress and leading to breast cancer ferroptosis therapy. Interestingly, the consumption of GSH can also reduce cisplatin inactivation, enhance the sensitivity of tumor cells to cisplatin and efficiently induce apoptosis/ferroptosis. This work highlights the use of GSH scavenger for triggering ferroptotic cell death in breast cancer.
- Cisplatin,
- Ferroptosis,
- Cancer therapy,
- Glutathione depletion,
- Tetravalent platinum prodrug
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