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...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.展开更多
基金financially supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions and Double First-classUniversity Projects(No.CPU2018GY06)Six Talent Peaks Projectin Jiangsu Province(No.WSW-112)+1 种基金Zhejiang province basic public welfare research project(No.LGN20C180001)Wenzhou Engineering Research Center of Pet(No.WP02)。
文摘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.
