Acta Pharmaceutica Sinica B (Dec 2021)
Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1
- Na Kong,
- Xiaying Chen,
- Jiao Feng,
- Ting Duan,
- Shuiping Liu,
- Xueni Sun,
- Peng Chen,
- Ting Pan,
- Lili Yan,
- Ting Jin,
- Yu Xiang,
- Quan Gao,
- Chengyong Wen,
- Weirui Ma,
- Wencheng Liu,
- Mingming Zhang,
- Zuyi Yang,
- Wengang Wang,
- Ruonan Zhang,
- Bi Chen,
- Tian Xie,
- Xinbing Sui,
- Wei Tao
Affiliations
- Na Kong
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
- Xiaying Chen
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Jiao Feng
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Ting Duan
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Shuiping Liu
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Xueni Sun
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Peng Chen
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Ting Pan
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Lili Yan
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Ting Jin
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Yu Xiang
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Quan Gao
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Chengyong Wen
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Weirui Ma
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Wencheng Liu
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Mingming Zhang
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Zuyi Yang
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Wengang Wang
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Ruonan Zhang
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Bi Chen
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China
- Tian Xie
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China; Corresponding authors.
- Xinbing Sui
- College of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines; Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China; Corresponding authors.
- Wei Tao
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Corresponding authors.
- Journal volume & issue
-
Vol. 11,
no. 12
pp. 4045 – 4054
Abstract
Ferroptosis is a non-apoptotic regulated cell death caused by iron accumulation and subsequent lipid peroxidation. Currently, the therapeutic role of ferroptosis on cancer is gaining increasing interest. Baicalin an active component in Scutellaria baicalensis Georgi with anticancer potential various cancer types; however, the effects of baicalein on bladder cancer and the underlying molecular mechanisms remain largely unknown. In the study, we investigated the effect of baicalin on bladder cancer cells 5637 and KU-19-19. As a result, we show baicalin exerted its anticancer activity by inducing apoptosis and cell death in bladder cancer cells. Subsequently, we for the first time demonstrate baicalin-induced ferroptotic cell death in vitro and in vivo, accompanied by reactive oxygen species (ROS) accumulation and intracellular chelate iron enrichment. The ferroptosis inhibitor deferoxamine but not necrostatin-1, chloroquine (CQ), N-acetyl-l-cysteine, l-glutathione reduced, or carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]-fluoromethylketone (Z-VAD-FMK) rescued baicalin-induced cell death, indicating ferroptosis contributed to baicalin-induced cell death. Mechanistically, we show that ferritin heavy chain 1 (FTH1) was a key determinant for baicalin-induced ferroptosis. Overexpression of FTH1 abrogated the anticancer effects of baicalin in both 5637 and KU19-19 cells. Taken together, our data for the first time suggest that the natural product baicalin exerts its anticancer activity by inducing FTH1-dependent ferroptosis, which will hopefully provide a prospective compound for bladder cancer treatment.